673 results on '"Lawrence A Leiter"'
Search Results
2. Effect of oats and oat ß-glucan on glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled trials
- Author
-
Tauseef A Khan, Fei Au-Yeung, Sonia Blanco Mejia, Lawrence A Leiter, John L Sievenpiper, Cyril W C Kendall, David J A Jenkins, Laura Chiavaroli, Amna Ahmed, Victoria Chen, and Andreea Zurbau
- Subjects
Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Introduction Current health claims recognize the ability of oat ß-glucan to lower blood cholesterol; however, its ability to improve glycemic control is less certain. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to update the evidence on the effect of oats and oat ß-glucan on glycemic control in individuals with diabetes.Research design and methods MEDLINE, EMBASE and Cochrane were searched (June 2021) for RCTs of ≥2 weeks investigating the effect of oat ß-glucan on glycemic control in diabetes. The outcomes were hemoglobin A1c (HbA1c), fasting glucose, 2-hour postprandial glucose (2h-PG) from a 75 g oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR) and fasting insulin. Independent reviewers extracted the data and assessed the risk of bias. Data were pooled using the generic inverse variance method. Heterogeneity was assessed (Cochran Q) and quantified (I2). Pooled estimates were expressed as mean difference (MD) with 95% CI. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach.Results Eight trial comparisons (n=407) met the eligibility criteria. All trials were in adults with type 2 diabetes who were predominantly middle-aged, overweight and treated by antihyperglycemic medications or insulin. A median dose of 3.25 g of oat ß-glucan for a median duration of 4.5 weeks improved HbA1c (MD, −0.47% (95% CI −0.80 to −0.13), pMD=0.006), fasting glucose (−0.75 mmol/L (−1.20 to –0.31), pMD
- Published
- 2022
- Full Text
- View/download PDF
3. A Web-Based Health Application to Translate Nutrition Therapy for Cardiovascular Risk Reduction in Primary Care (PortfolioDiet.app): Quality Improvement and Usability Testing Study
- Author
-
Meaghan E Kavanagh, Laura Chiavaroli, Andrea J Glenn, Genevieve Heijmans, Shannan M Grant, Chi-Ming Chow, Robert G Josse, Vasanti S Malik, William Watson, Aisha Lofters, Candice Holmes, Julia Rackal, Kristie Srichaikul, Diana Sherifali, Erna Snelgrove-Clarke, Jacob A Udell, Peter Juni, Gillian L Booth, Michael E Farkouh, Lawrence A Leiter, Cyril W C Kendall, David J A Jenkins, and John L Sievenpiper
- Subjects
Medical technology ,R855-855.5 - Abstract
BackgroundThe Portfolio Diet, or Dietary Portfolio, is a therapeutic dietary pattern that combines cholesterol-lowering foods to manage dyslipidemia for the prevention of cardiovascular disease. To translate the Portfolio Diet for primary care, we developed the PortfolioDiet.app as a patient and physician educational and engagement tool for PCs and smartphones. The PortfolioDiet.app is currently being used as an add-on therapy to the standard of care (usual care) for the prevention of cardiovascular disease in primary care. To enhance the adoption of this tool, it is important to ensure that the PortfolioDiet.app meets the needs of its target end users. ObjectiveThe main objective of this project is to undertake user testing to inform modifications to the PortfolioDiet.app as part of ongoing engagement in quality improvement (QI). MethodsWe undertook a 2-phase QI project from February 2021 to September 2021. We recruited users by convenience sampling. Users included patients, family physicians, and dietitians, as well as nutrition and medical students. For both phases, users were asked to use the PortfolioDiet.app daily for 7 days. In phase 1, a mixed-form questionnaire was administered to evaluate the users’ perceived acceptability, knowledge acquisition, and engagement with the PortfolioDiet.app. The questionnaire collected both quantitative and qualitative data, including 2 open-ended questions. The responses were used to inform modifications to the PortfolioDiet.app. In phase 2, the System Usability Scale was used to assess the usability of the updated PortfolioDiet.app, with a score higher than 70 being considered acceptable. ResultsA total of 30 and 19 users were recruited for phase 1 and phase 2, respectively. In phase 1, the PortfolioDiet.app increased users’ perceived knowledge of the Portfolio Diet and influenced their perceived food choices. Limitations identified by users included challenges navigating to resources and profile settings, limited information on plant sterols, inaccuracies in points, timed-logout frustration, request for step-by-step pop-up windows, and request for a mobile app version; when looking at positive feedback, the recipe section was the most commonly praised feature. Between the project phases, 6 modifications were made to the PortfolioDiet.app to incorporate and address user feedback. At phase 2, the average System Usability Scale score was 85.39 (SD 11.47), with 100 being the best possible. ConclusionsBy undertaking user testing of the PortfolioDiet.app, its limitations and strengths were able to be identified, informing modifications to the application, which resulted in a clinical tool that better meets users’ needs. The PortfolioDiet.app educates users on the Portfolio Diet and is considered acceptable by users. Although further refinements to the PortfolioDiet.app will continue to be made before its evaluation in a clinical trial, the result of this QI project is an improved clinical tool.
- Published
- 2022
- Full Text
- View/download PDF
4. Ongoing clinical trials of the pleiotropic effects of statins
- Author
-
Jean Davignon and Lawrence A Leiter
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Jean Davignon1, Lawrence A Leiter21Clinical Research Institute of Montreal, Montreal, QC, Canada; 2Division of Endocrinology and Metabolism, St Michael’s Hospital, Toronto, ON, CanadaBackground: The multiple effects (ie, pleiotropic effects of statins) have received increasing recognition and may have clinical applicability across a broad range of cardiovascular and noncardiovascular conditions. Objective: To determine the relevance and significance of ongoing clinical trials of the pleiotropic effects of statins, focusing on nonlipid effects. Method: Ongoing trials were identified through personal communication, reports presented at scientific meetings (2000–2004), and queries made to AstraZeneca, Bristol-Myers Squibb Co, Merck & Co, Novartis, and Pfizer, manufacturers of the currently marketed statins. Published trials and other source material were identified through electronic searches on MEDLINE (1990–2003), abstract books, and references identified from bibliographies of pertinent articles. Eligible studies were the clinical trials of statins currently under way in which primary or secondary outcomes included the statins’ nonlipid (ie, pleiotropic) effect(s). Data were extracted and trial quality was assessed by the authors. Results: Of the 22 ongoing trials of the nonlipid effects of statins identified, 10 assessed inflammatory markers and plaque stabilization, 4 assessed oxidized low density lipoprotein/vascular oxidant stress, 3 assessed end-stage renal disease, 3 assessed fibrinogen/viscosity, 2 assessed endothelial function, 2 assessed acute coronary syndrome, 2 assessed aortic stenosis progression, and 1 each assessed hypertension, osteoporosis, ischemic burden, Alzheimer’s disease, multiple sclerosis, and stroke (outcomes often overlapped). Conclusion: Given the excellent safety and tolerability of statins as a class, full exploration of their pleiotropic effects has the potential to provide additional benefits to many patients. Keywords: atherosclerosis, cholesterol, clinical trials, endothelium, lipoproteins, metabolism, myocardial infarction, pharmacology, vasculature
- Published
- 2005
5. Effect of tree nuts on glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled dietary trials.
- Author
-
Effie Viguiliouk, Cyril W C Kendall, Sonia Blanco Mejia, Adrian I Cozma, Vanessa Ha, Arash Mirrahimi, Viranda H Jayalath, Livia S A Augustin, Laura Chiavaroli, Lawrence A Leiter, Russell J de Souza, David J A Jenkins, and John L Sievenpiper
- Subjects
Medicine ,Science - Abstract
Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.Two independent reviewer's extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI's. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2).Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = -0.07% [95% CI:-0.10, -0.03%]; P = 0.0003) and fasting glucose (MD = -0.15 mmol/L [95% CI: -0.27, -0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.Majority of trials were of short duration and poor quality.Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.ClinicalTrials.gov NCT01630980.
- Published
- 2014
- Full Text
- View/download PDF
6. Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study
- Author
-
Erin S. Mackinnon, Lawrence A. Leiter, Rajvi J. Wani, Natasha Burke, Eileen Shaw, Kelcie Witges, and Shaun G. Goodman
- Subjects
Atherosclerotic cardiovascular disease ,Cardiovascular events ,Acute coronary syndrome ,Acute myocardial infarction ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Introduction The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Methods Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. Results The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). Conclusion This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.
- Published
- 2024
- Full Text
- View/download PDF
7. Review of Evolocumab for the Reduction of LDL Cholesterol and Secondary Prevention of Atherosclerotic Cardiovascular Disease
- Author
-
Lawrence A. Leiter, Robert A. Hegele, Vivien Brown, Jean Bergeron, Erin S. Mackinnon, and G. B. John Mancini
- Subjects
evolocumab ,proprotein convertase subtilisin-kexin type 9 (pcsk9) inhibitor ,lipid-lowering therapy ,low-density lipoprotein cholesterol (ldl-c) ,atherosclerotic cardiovascular disease (ascvd) ,cardiovascular outcomes ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of >60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of >90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in >51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.
- Published
- 2024
- Full Text
- View/download PDF
8. Important food sources of fructose-containing sugars and adiposity: A systematic review and meta-analysis of controlled feeding trials
- Author
-
Laura Chiavaroli, Annette Cheung, Sabrina Ayoub-Charette, Amna Ahmed, Danielle Lee, Fei Au-Yeung, XinYe Qi, Songhee Back, Néma McGlynn, Vanessa Ha, Ethan Lai, Tauseef A. Khan, Sonia Blanco Mejia, Andreea Zurbau, Vivian L. Choo, Russell J. de Souza, Thomas MS. Wolever, Lawrence A. Leiter, Cyril WC. Kendall, David JA. Jenkins, and John L. Sievenpiper
- Subjects
Nutrition and Dietetics ,Medicine (miscellaneous) - Published
- 2023
9. Cost-Effectiveness of Icosapent Ethyl (IPE) for the Reduction of the Risk of Ischemic Cardiovascular Events in Canada
- Author
-
Jean Lachaine, Jean-Nicolas Charron, Jean C Gregoire, Robert A Hegele, and Lawrence A Leiter
- Subjects
ClinicoEconomics and Outcomes Research ,Health Policy ,Economics, Econometrics and Finance (miscellaneous) - Abstract
Jean Lachaine,1,2 Jean-Nicolas Charron,2 Jean C Gregoire,3 Robert A Hegele,4 Lawrence A Leiter5 1University of Montreal, Montreal, QC, Canada; 2PeriPharm Inc., Montreal, QC, Canada; 3Institut de cardiologie de Montréal, Montreal, QC, Canada; 4Robarts Research Institute, London, ON, Canada; 5Li Ka Shing Knowledge Institute, St. Michaelâs Hospital, University of Toronto, Toronto, ON, CanadaCorrespondence: Jean Lachaine, Faculty of Pharmacy University of Montreal, 2900 Edouard-Montpetit Blvd, Montreal, Quebec, H3T 1J4, Canada, Email jean.lachaine@umontreal.caBackground: Despite the use of statins, many patients with cardiovascular disease (CVD) have persistent residual risk. In a large Phase III trial (REDUCE-IT), icosapent ethyl (IPE) was shown to reduce the first occurrence of the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina.Methods: We conducted a cost-utility analysis comparing IPE to placebo in statin-treated patients with elevated triglycerides, from a publicly funded, Canadian healthcare payer perspective, using a time-dependent Markov transition model over a 20-year time horizon. We obtained efficacy and safety data from REDUCE-IT, and costs and utilities from provincial formularies and databases, manufacturer sources, and Canadian literature sources.Results: In the probabilistic base-case analysis, IPE was associated with an incremental cost of $12,523 and an estimated 0.29 more quality-adjusted life years (QALYs), corresponding to an incremental cost-effectiveness ratio (ICER) of $42,797/QALY gained. At a willingness-to-pay of $50,000 and $100,000/QALY gained, there is a probability of 70.4% and 98.8%, respectively, that IPE is a cost-effective strategy over placebo. The deterministic model yielded similar results. In the deterministic sensitivity analyses, the ICER varied between $31,823-$70,427/QALY gained. Scenario analyses revealed that extending the timeframe of the model to a lifetime horizon resulted in an ICER of $32,925/QALY gained.Conclusion: IPE represents an important new treatment for the reduction of ischemic CV events in statin-treated patients with elevated triglycerides. Based on the clinical trial evidence, we found that IPE could be a cost-effective strategy for treating these patients in Canada.Keywords: cardiovascular diseases, icosapent ethyl, IPE, cost-effectiveness, cost per QALY
- Published
- 2023
10. Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies
- Author
-
Tauseef A. Khan, David Field, Victoria Chen, Suleman Ahmad, Sonia Blanco Mejia, Hana Kahleová, Dario Rahelić, Jordi Salas-Salvadó, Lawrence A. Leiter, Matti Uusitupa, Cyril W.C. Kendall, and John L. Sievenpiper
- Subjects
Advanced and Specialized Nursing ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
OBJECTIVECombined low-risk lifestyle behaviors (LRLBs) have been associated with a reduction in type 2 diabetes risk. This relationship has not been systematically quantified.RESEARCH DESIGN AND METHODSA systematic review and meta-analysis was conducted to assess the association of combined LRLBs with type 2 diabetes. Databases were searched up to September 2022. Prospective cohort studies reporting the association between a minimum of three combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using a random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using a one-stage linear mixed model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).RESULTSThirty cohort comparisons (n = 1,693,753) involving 75,669 incident type 2 diabetes cases were included. LRLBs, with author-defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk [RR] 0.20; 95% CI 0.17–0.23), comparing the highest with lowest adherence. Global DRM for maximum adherence to all five LRLBs reached 85% protection (RR 0.15; 95% CI 0.12–0.18). The overall certainty of the evidence was graded as high.CONCLUSIONSThere is a very good indication that a combination of LRLBs that includes maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption is associated with a lower risk of incident type 2 diabetes.
- Published
- 2023
11. Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial
- Author
-
Kim A. Connelly, C. David Mazer, Pankaj Puar, Hwee Teoh, Chao-Hung Wang, Tamique Mason, Farhad Akhavein, Ching-Wen Chang, Min-Hui Liu, Ning-I Yang, Wei-Siang Chen, Yu-Hsiang Juan, Erika Opingari, Yaseen Salyani, William Barbour, Aryan Pasricha, Shamon Ahmed, Andrew Kosmopoulos, Raj Verma, Michael Moroney, Ehab Bakbak, Aishwarya Krishnaraj, Deepak L. Bhatt, Javed Butler, Mikhail N. Kosiborod, Carolyn S.P. Lam, David A. Hess, Otavio Rizzi Coelho-Filho, Myriam Lafreniere-Roula, Kevin E. Thorpe, Adrian Quan, Lawrence A. Leiter, Andrew T. Yan, and Subodh Verma
- Subjects
Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Sodium-glucose cotransporter 2 inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. Although it has been theorized that sodium-glucose cotransporter 2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine whether sodium-glucose cotransporter 2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure. Methods: Between April 2021 and January 2022, 169 individuals, 40 to 80 years of age, without diabetes but with risk factors for adverse cardiac remodeling were randomly assigned to empagliflozin (10 mg/d; n=85) or placebo (n=84) for 6 months. The primary outcome was the 6-month change in LV mass indexed (LVMi) to baseline body surface area as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and LV end-systolic volumes indexed to baseline body surface area and LV ejection fraction. Results: Among the 169 participants (141 men [83%]; mean age, 59.3±10.5 years), baseline LVMi was 63.2±17.9 g/m 2 and 63.8±14.0 g/m 2 for the empagliflozin- and placebo-assigned groups, respectively. The difference (95% CI) in LVMi at 6 months in the empagliflozin group versus placebo group adjusted for baseline LVMi was –0.30 g/m 2 (–2.1 to 1.5 g/m 2 ; P =0.74). Median baseline (interquartile range) NT-proBNP (N-terminal-pro B-type natriuretic peptide) was 51 pg/mL (20–105 pg/mL) and 55 pg/mL (21–132 pg/mL) for the empagliflozin- and placebo-assigned groups, respectively. The 6-month treatment effect of empagliflozin versus placebo (95% CI) on blood pressure and NT-proBNP (adjusted for baseline values) were –1.3 mm Hg (–5.2 to 2.6 mm Hg; P =0.52), 0.69 mm Hg (–1.9 to 3.3 mm Hg; P =0.60), and –6.1 pg/mL (–37.0 to 24.8 pg/mL; P =0.70) for systolic blood pressure, diastolic blood pressure, and NT-proBNP, respectively. No clinically meaningful between-group differences in LV volumes (diastolic and systolic indexed to baseline body surface area) or ejection fraction were observed. No difference in adverse events was noted between the groups. Conclusions: Among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, sodium-glucose cotransporter 2 inhibition with empagliflozin did not result in a meaningful reduction in LVMi after 6 months. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04461041.
- Published
- 2023
12. External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry
- Author
-
Jeremie Abtan, Deepak L. Bhatt, Yedid Elbez, Gregory Ducrocq, Shinya Goto, Sidney C. Smith, E. Magnus Ohman, Kim A. Eagle, Kim Fox, Robert A. Harrington, Lawrence A. Leiter, Shamir R. Mehta, Tabassome Simon, Ivo Petrov, Peter R. Sinnaeve, Prem Pais, Eli Lev, Héctor Bueno, Peter Wilson, Philippe Gabriel Steg, and AstraZeneca
- Subjects
Ticagrelor ,Cardiac & Cardiovascular Systems ,RANDOMIZED CONTROLLED-TRIALS ,Myocardial Infarction ,ELIGIBILITY ,Coronary Artery Disease ,Diabetes mellitus ,Percutaneous Coronary Intervention ,Outcome Assessment, Health Care ,CRITERIA ,Humans ,VALIDITY ,RISK ,Science & Technology ,Aspirin ,CARDIOVASCULAR EVENT RATES ,Stroke ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular System & Cardiology ,Stable coronary artery disease ,PRIMARY PREVENTION ,OUTPATIENTS ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,CLINICAL-TRIALS ,Platelet Aggregation Inhibitors - Abstract
THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.' http://www. gov identifier: NCT01991795. The THEMIS trial was funded by AstraZeneca. The REACH registry was sponsored by Sanofi, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan) and is endorsed by the World Heart Federation. Sí
- Published
- 2023
13. Ease of Use of the iGlarLixi SoloStar Pen from the LixiLan ONE CAN Pen Sub-Study: Questionnaire Findings from People Living with Type 2 Diabetes and Their HealthCare Providers
- Author
-
Jean-François Yale, Aude Roborel de Climens, Naresh Aggarwal, Terry Dex, Hertzel C. Gerstein, Stewart Harris, Irene Hramiak, John Stewart, and Lawrence A. Leiter
- Subjects
Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
For people with type 2 diabetes mellitus who do not achieve glycated hemoglobin A1C targets after treatment with basal insulin therapies, additional therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) may be required. One option is to use a once-daily fixed-ratio combination (FRC) of basal insulin and a GLP-1 RA such as iGlarLixi (which is composed of insulin glargine 100 U/ml and lixisenatide). However, the ease of transitioning from basal insulin to an FRC has not been studied.This sub-study of the LixiLan ONE CAN trial (NCT03767543) was conducted to assess the ease of transitioning from insulin glargine 100 U/ml to the FRC, iGlarLixi, using the iGlarLixi SoloStarOverall, 95.1% of patients reported that the iGlarLixi Solostar pen was "easy" or "very easy" to use. Similarly, 100% of HCPs reported that it was "easy" or "very easy" to train people to use the pen. Nearly all participants (97.5% of patients and 94% of HCPs) responded that they would recommend the iGlarLixi Solostar pen to others.These results suggest that during the transition from insulin glargine 100 U/ml to iGlarLixi, there were no difficulties associated with using the iGlarLixi SoloStar pen injector regarding instruction for use by HCPs or actual use by the majority of patients. The results indicate a broad consensus between patients and HCPs on the relative simplicity of transitioning from self-administration of insulin glargine 100 U/ml to iGlarLixi.ClinicalTrials.gov identifier, NCT03767543; Date of registration: December 6, 2018; Retrospectively registered.Many people take basal insulin to control their blood sugar, but for those in whom basal insulin injections do not work well enough to achieve their target blood glucose, treatment needs to be advanced. One option to do this is with a fixed-ratio combination therapy that combines basal insulin with a GLP-1 receptor agonist, such as iGlarLixi. Both basal insulin and fixed-ratio combination therapies are administered using injection pens, but the ease of transitioning from a basal insulin pen to a fixed-ratio combination pen has not been assessed. In this study, people with type 2 diabetes who had previously received the basal insulin insulin glargine 100 U/ml using a SoloStar
- Published
- 2022
14. Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial
- Author
-
David J.A. Jenkins, Laura Chiavaroli, Arash Mirrahimi, Sandra Mitchell, Dorothea Faulkner, Sandhya Sahye-Pudaruth, Melanie Paquette, Judy Coveney, Omodele Olowoyeye, Darshna Patel, Sathish Chandra Pichika, Balachandran Bashyam, Tishan Maraj, Chantal Gillett, Russell J. de Souza, Livia S.A. Augustin, Sonia Blanco Mejia, Stephanie K. Nishi, Lawrence A. Leiter, Robert G. Josse, Gail E. McKeown-Eyssen, Alan R. Berger, Philip W. Connelly, Korbua Srichaikul, Cyril W.C. Kendall, John L. Sievenpiper, and Alan R. Moody
- Subjects
Male ,Dietary Fiber ,Blood Glucose ,Advanced and Specialized Nursing ,Diabetes Mellitus, Type 2 ,Glycemic Index ,Cardiovascular Diseases ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Humans ,Female ,Triticum ,Diet - Abstract
OBJECTIVE High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI −10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.
- Published
- 2022
15. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials
- Author
-
Kausik K, Ray, Frederick J, Raal, David G, Kallend, Mark J, Jaros, Wolfgang, Koenig, Lawrence A, Leiter, Ulf, Landmesser, Gregory G, Schwartz, David, Lawrence, Andrew, Friedman, Lorena, Garcia Conde, and R Scott, Wright
- Subjects
Cardiology and Cardiovascular Medicine - Abstract
Background Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established. Methods and results Patient-level, pooled analysis of ORION-9, −10 and −11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58–0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50–1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41–1.81)]. Conclusion This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.
- Published
- 2022
16. Low-carbohydrate vegan diets in diabetes for weight loss and sustainability: a randomized controlled trial
- Author
-
David J A, Jenkins, Peter J H, Jones, Mohammad M H, Abdullah, Benoit, Lamarche, Dorothea, Faulkner, Darshna, Patel, Sandhya, Sahye-Pudaruth, Melanie, Paquette, Balachandran, Bashyam, Sathish C, Pichika, Meaghan E, Kavanagh, Pooja, Patel, Fred, Liang, Ramon, Brown, Tiffany, Zhao, Mila, Phan, Gajuna, Mathiyalagan, Shilpa, Tandon, Vladmir, Vuksan, Elena, Jovanovski, John L, Sievenpiper, Cyril W C, Kendall, Lawrence A, Leiter, and Robert G, Josse
- Subjects
Nutrition and Dietetics ,Medicine (miscellaneous) - Abstract
Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option.We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes.One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants.Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (-5.9 kg; 95% CI: -6.5, -5.28 kg; and -5.23 kg; 95% CI: -5.84, -4.62 kg), glycated hemoglobin (-0.99%; 95% CI: -1.07, -0.9%; and -0.88%; 95% CI: -0.97, -0.8%), systolic blood pressure (-4 mmHg; 95% CI: -7, -2 mmHg; and -6 mmHg; 95% CI: -8, -3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of -0.63 kgCO2/d (95% CI: -0.99, -0.27 kgCO2/d) favoring the low-carbohydrate vegan diet.Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions.Trial registration number: clinicaltrials.gov identifier NCT02245399.
- Published
- 2022
17. Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes
- Author
-
Ofri Mosenzon, Itamar Raz, Stephen D. Wiviott, Meir Schechter, Erica L. Goodrich, Ilan Yanuv, Aliza Rozenberg, Sabina A. Murphy, Thomas A. Zelniker, Anna Maria Langkilde, Ingrid A.M. Gause-Nilsson, Martin Fredriksson, Peter A. Johansson, John P.H. Wilding, Darren K. McGuire, Deepak L. Bhatt, Lawrence A. Leiter, Avivit Cahn, Jamie P. Dwyer, Hiddo J.L. Heerspink, Marc S. Sabatine, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
- Subjects
Advanced and Specialized Nursing ,Glucose ,Diabetes Mellitus, Type 2 ,Glucosides ,Endocrinology, Diabetes and Metabolism ,Sodium ,Myocardial Infarction ,Internal Medicine ,Humans ,Diabetic Nephropathies ,Benzhydryl Compounds ,Sodium-Glucose Transporter 2 Inhibitors ,Glomerular Filtration Rate - Abstract
OBJECTIVE In patients with moderate to severe albuminuric kidney disease, sodium–glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to RESULTS Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38–0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001). CONCLUSIONS Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease.
- Published
- 2022
18. Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post‐hoc analysis from the REWIND randomized trial
- Author
-
Kelley R.H. Branch, Gilles R. Dagenais, Alvaro Avezum, Jan Basile, Ignacio Conget, William C. Cushman, Petr Jansky, Mark Lakshmanan, Fernando Lanas, Lawrence A. Leiter, Prem Pais, Nana Pogosova, Peter J. Raubenheimer, Lars Ryden, Jonathan E. Shaw, Wayne H.H. Sheu, Theodora Temelkova‐Kurktschiev, M. Angelyn Bethel, Hertzel C. Gerstein, Ramasundarahettige Chinthanie, and Jeffrey L. Probstfield
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
19. Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6
- Author
-
W. David Strain, Ofir Frenkel, Martin A. James, Lawrence A. Leiter, Søren Rasmussen, Peter M. Rothwell, Maria Sejersten Ripa, Thomas C. Truelsen, and Mansoor Husain
- Subjects
Advanced and Specialized Nursing ,prevalence ,Glucagon-Like Peptides ,blood pressure ,Stroke ,myocardial infarction ,Diabetes Mellitus, Type 2 ,Atrial Fibrillation ,peptides ,Humans ,Hypoglycemic Agents ,atrial fibrillation ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk. Methods: SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction P values. Risk of major adverse cardiovascular event was analyzed according to prior stroke. Results: A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46–1.00]; P =0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29–0.89]; P =0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37–0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47–1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation ( P interaction =0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke ( P interaction >0.05 for all). Conclusions: Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01720446 and NCT02692716.
- Published
- 2022
20. 2022 Canadian Cardiovascular Society Guideline for Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors for Cardiorenal Risk Reduction in Adults
- Author
-
G.B. John Mancini, Eileen O’Meara, Shelley Zieroth, Mathieu Bernier, Alice Y.Y. Cheng, David Z.I. Cherney, Kim A. Connelly, Justin Ezekowitz, Ronald M. Goldenberg, Lawrence A. Leiter, Gihad Nesrallah, Breay W. Paty, Marie-Eve Piché, Peter Senior, Abhinav Sharma, Subodh Verma, Vincent Woo, Pol Darras, Jonathan Y. Gabor, Jean Grégoire, Eva Lonn, James A. Stone, Jean-François Yale, Colin Yeung, and Deborah Zimmerman
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
21. Neutrophil to lymphocyte ratio predicts cardiovascular events in people with type 2 diabetes: Post hoc analysis of the <scp>SUSTAIN</scp> 6 and <scp>PIONEER</scp> 6 cardiovascular outcomes trials
- Author
-
Subodh Verma, Mansoor Husain, Christian M. Madsen, Lawrence A. Leiter, Anja Birk Kuhlman, Tina Vilsbøll, Søren Rasmussen, and Peter Libby
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2023
22. Semaglutide reduces the risk of major adverse cardiovascular events consistently across baseline triglyceride levels in patients with type 2 diabetes: Post hoc analyses of the <scp>SUSTAIN</scp> 6 and <scp>PIONEER</scp> 6 trials
- Author
-
Subodh Verma, Jens‐Peter David, Lawrence A. Leiter, Marie Mide Michelsen, Søren Rasmussen, and Deepak L. Bhatt
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2023
23. Biomarkers for the Diagnosis of Heart Failure in People with Diabetes: A Consensus Report from Diabetes Technology Society
- Author
-
Andrea M. Yeung, Jingtong Huang, Ambarish Pandey, Ibrahim A. Hashim, David Kerr, Rodica Pop-Busui, Connie M. Rhee, Viral N. Shah, Lia Bally, Antoni Bayes-Genis, Yong Mong Bee, Richard Bergenstal, Javed Butler, G. Alexander Fleming, Gregory Gilbert, Stephen J. Greene, Mikhail N. Kosiborod, Lawrence A. Leiter, Boris Mankovsky, Thomas W. Martens, Chantal Mathieu, Viswanathan Mohan, Kershaw V. Patel, Anne Peters, Eun-Jung Rhee, Giuseppe M.C. Rosano, David B. Sacks, Yader Sandoval, Jane Jeffrie Seley, Oliver Schnell, Guillermo Umpierrez, Kayo Waki, Eugene E. Wright, Alan H.B. Wu, and David C. Klonoff
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2023
24. Comparing a daily versus weekly titration algorithm in people with type 2 diabetes switching from basal insulin to <scp>iGlarLixi</scp> in the <scp>LixiLan ONE CAN</scp> randomized trial
- Author
-
Irene Hramiak, Hertzel C. Gerstein, Lawrence A. Leiter, Jean‐François Yale, Harpreet S. Bajaj, John Stewart, Marie‐Josée Toutounji, and Stewart B. Harris
- Subjects
Blood Glucose ,Glycated Hemoglobin ,Drug Combinations ,Endocrinology ,Diabetes Mellitus, Type 2 ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Humans ,Hypoglycemic Agents ,Insulin Glargine ,Peptides ,Algorithms - Abstract
To compare the efficacy and safety of a simple daily titration algorithm compared with a weekly dose adjustment of iGlarLixi in people with type 2 diabetes.LixiLan ONE CAN (NCT03767543), a randomized, 26-week, open-label, multicentre phase 3 trial conducted in Canada, involved 265 people with type 2 diabetes and an HbA1c of ≥7.5% to ≤ 10.5% or less (≥58 to ≤91 mmol/mol) on basal insulin for 6 months or longer. Participants were randomized 1:1 with instructions to self-titrate iGlarLixi daily (1 unit/day) or once weekly (2 or 4 units/week) to a common target fasting plasma glucose of 4.4 to 5.6 mmol/L (79 to 101 mg/dl). The primary objective was to show non-inferiority of the daily versus weekly titration algorithm.At 26 weeks, daily titration of iGlarLixi was not inferior to a weekly titration for both the prespecified primary endpoint of change in HbA1c from baseline (least square [LS] mean change: -1.24% vs. -0.92%, respectively; LS mean difference: 0.32%; 95% CI [0.07, 0.57]; P .0001) and for the secondary endpoint of change in weight from baseline (LS mean change: -0.22 vs. +0.81 kg, respectively; LS mean difference: 1.03 kg; 95% CI [0.01, 2.06]; P .0001). Indeed, for both the primary and secondary outcome, the daily titration of iGlarLixi was superior. There were no statistically significant differences in hypoglycaemia incidence between the two titration strategies during the 26-week study.A daily titration algorithm for switching basal insulin to iGlarLixi was shown to be non-inferior and superior for glycaemic control and weight compared with weekly titration.
- Published
- 2022
25. Author response for 'Semaglutide reduces risk of <scp>MACE</scp> consistently across baseline triglyceride levels in patients with type 2 diabetes: Post Hoc Analyses of <scp>SUSTAIN</scp> 6 and <scp>PIONEER</scp> 6 trials'
- Author
-
null Subodh Verma, null Jens‐Peter David, null Lawrence A. Leiter, null Marie Mide Michelsen, null Søren Rasmussen, and null Deepak L. Bhatt
- Published
- 2023
26. Author response for 'Neutrophil–lymphocyte ratio predicts cardiovascular events in people with type 2 diabetes: post hoc analysis of the <scp>SUSTAIN</scp> 6 and <scp>PIONEER</scp> 6 cardiovascular outcomes trials'
- Author
-
null Subodh Verma, null Mansoor Husain, null Christian Medom Madsen, null Lawrence A. Leiter, null Anja Birk Kuhlman, null Tina Vilsbøll, null Søren Rasmussen, and null Peter Libby
- Published
- 2023
27. Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study
- Author
-
Sabrina Ayoub-Charette, Néma D. McGlynn, Danielle Lee, Tauseef Ahmad Khan, Sonia Blanco Mejia, Laura Chiavaroli, Meaghan E. Kavanagh, Maxine Seider, Amel Taibi, Chuck T. Chen, Amna Ahmed, Rachel Asbury, Madeline Erlich, Yue-Tong Chen, Vasanti S. Malik, Richard P. Bazinet, D. Dan Ramdath, Caomhan Logue, Anthony J. Hanley, Cyril W. C. Kendall, Lawrence A. Leiter, Elena M. Comelli, and John L. Sievenpiper
- Subjects
glycemia ,glucose control ,Nutrition and Dietetics ,gut microbiota ,water ,randomized controlled trial ,overweight ,low- and no-calorie sweeteners ,type 2 diabetes ,sweetening agents ,sugar-sweetened beverages ,Food Science - Abstract
Background: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the “intended substitution”) versus water (the “standard of care substitution”) for SSBs on glucose tolerance and microbiota diversity. Design and Methods: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, “head-to-head”, open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. Baseline results: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). Conclusions: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. Trial registration: ClinicalTrials.gov identifier, NCT03543644.
- Published
- 2023
- Full Text
- View/download PDF
28. Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies
- Author
-
Lawrence A Leiter, Jordi Salas-Salvadó, Dario Rahelić, Hana Kahleová, Sonia Blanco Mejia, Suleman Ahmad, Victoria Chen, David Field, and Tauseef A Khan
- Abstract
Objective: Combined low-risk lifestyle behaviors (LRLBs) have been associated with reduction in type 2 diabetes risk. This relationship has not been systematically quantified. Research design and methods: A systematic review and meta-analysis was conducted to assess the association of combined low-risk lifestyle behaviors with type 2 diabetes. Databases was searched up to September 2022. Prospective cohort studies reporting the association between a minimum of 3 combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using one-stage linear mixed model. The certainty of the evidence was assessed using GRADE. Results: 30 cohort comparisons (n=1,693,753) involving 75,669 incident type 2 diabetes cases were eligible. LRLBs, with author defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk (RR), 0.20 [95% confidence interval, 0.17 to 0.23]), comparing the highest with lowest adherence. Global DRM for maximum adherence to all 5 LRLBs reached 85% protection (RR, 0.15 [95% CI, 0.12 to 0.18]. The overall certainty of the evidence was graded as high. Conclusions: There was a very good indication that combination of LRLBs that include maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation and light alcohol consumption was associated with a lower risk of incident type 2 diabetes. Study registration: ClinicalTrials.gov (NCT03234101)
- Published
- 2023
29. Efficacy and safety of bempedoic acid in women with hypercholesterolemia: Pooled analyses from phase 3 trials
- Author
-
Anne C. Goldberg, Maciej Banach, Alberico L. Catapano, P. Barton Duell, Lawrence A. Leiter, Jeffrey C. Hanselman, Lei Lei, and G.B. John Mancini
- Abstract
Background and aimsSex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.MethodsPatients were grouped into two pools: atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) “on statins”, and “low-dose or no statin”. Percent changes from baseline to at least week 12 in low-density lipoprotein-cholesterol (LDL-C), non–high-density lipoprotein-cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex.ResultsOverall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acidvs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p≤0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2%vs. −17.4%;p=0.044), non–HDL-C (−17.3%vs. −12.1%;p=0.003), TC (−13.8%vs. −10.5%;p=0.012), and Apo B (−16.0%vs. −11.3%;p=0.004) in the ASCVD and/or HeFH on statins pool. Women had numerically greater reductions than men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes.ConclusionsIn this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.
- Published
- 2023
30. Cost–effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease: a European economic evaluation of the THEMIS trial
- Author
-
Philippe Gabriel Steg, Deepak L Bhatt, Stefan K James, Oliver Darlington, Louise Hoskin, Tabassome Simon, Kim M Fox, Lawrence A Leiter, Shamir R Mehta, Robert A Harrington, Anders Himmelmann, Wilhelm Ridderstråle, Marielle Andersson, Héctor Bueno, Leonardo De Luca, Amarjeet Tank, Carl Mellström, Phil McEwan, and AstraZeneca
- Subjects
Ticagrelor ,Kardiologi ,Percutaneous Coronary Intervention ,Diabetes Mellitus, Type 2 ,Aspirin ,Cost-Benefit Analysis ,Humans ,Type 2 diabetes ,Cardiac and Cardiovascular Systems ,Pharmacology (medical) ,Cost–effectiveness ,Coronary Artery Disease ,Cardiology and Cardiovascular Medicine - Abstract
Aims To conduct a health economic evaluation of ticagrelor in patients with type 2 diabetes and coronary artery disease (CAD) from a multinational payer perspective. Cost–effectiveness and cost–utility of ticagrelor were evaluated in the overall effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS) trial population and in the predefined patient group with prior percutaneous coronary intervention. Methods and results A Markov model was developed to extrapolate patient outcomes over a lifetime horizon. The primary outcome was incremental cost–effectiveness ratios (ICERs), which were compared with conventional willingness-to-pay thresholds [€47 000/quality-adjusted life-year (QALY) in Sweden and €30 000/QALY in other countries]. Treatment with ticagrelor resulted in QALY gains of up to 0.045 in the overall population and 0.099 in patients with percutaneous coronary intervention (PCI). Increased costs and benefits translated to ICERs ranged between €27 894 and €42 252/QALY across Sweden, Germany, Italy, and Spain in the overall population. In patients with prior PCI, estimated ICERs improved to €18 449, €20 632, €20 233, and €13 228/QALY in Sweden, Germany, Italy, and Spain, respectively, driven by higher event rates and treatment benefit. Conclusion Based on THEMIS results, ticagrelor plus aspirin compared with aspirin alone may be cost–effective in some European countries in patients with T2DM and CAD and no prior myocardial infarction (MI) or stroke. Additionally, ticagrelor is likely to be cost–effective across European countries in patients with a history of PCI.
- Published
- 2022
31. Glycemic Control and Cardiovascular Risk Factor Management in Adults With Type 2 Diabetes With and Without Chronic Kidney Disease Before Sodium-Glucose Cotransporter Protein 2 Inhibitors: Insights From the Diabetes Mellitus Status in Canada Survey
- Author
-
Ron Wald, Mary K. Tan, Kim A. Connelly, Anatoly Langer, Hwee Teoh, Lawrence A. Leiter, Hirmand Nouraei, Shaun G. Goodman, Alice Y.Y. Cheng, and Andrew T. Yan
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,Psychological intervention ,030209 endocrinology & metabolism ,Glycemic Control ,Type 2 diabetes ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,030212 general & internal medicine ,Renal Insufficiency, Chronic ,education ,Glycemic ,Glycated Hemoglobin ,education.field_of_study ,business.industry ,Cholesterol ,Sodium ,General Medicine ,medicine.disease ,Diabetes Mellitus, Type 2 ,chemistry ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Female ,Glycated hemoglobin ,business ,Kidney disease - Abstract
Optimal control of cardiovascular risk factors in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) is challenging. Limited data are available from the primary care setting on achievement of guideline-recommended targets in this population before the use of sodium-glucose cotransporter protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.The Diabetes Mellitus Status in Canada survey included 5,172 patients with T2D seen by primary care physicians (PCPs) in November 2012. We compared treatment targets and therapeutic interventions in patients with and without CKD.Compared with those without CKD (n=3,804), patients with CKD (n=1,368) were older, more likely to be female, had a longer duration of diabetes and had more vascular complications. Patients with CKD more frequently had a less stringent glycated hemoglobin (A1C) target of ≤8.0% set by PCPs (10.3% vs 20%, p0.001), and fewer patients with CKD met the A1C target of ≤7.0% (50.9% vs 47.1%, p=0.016) than those without CKD. Both groups had a similar likelihood of achieving the blood pressure (BP) target of ≤130/80 mmHg (36.8% vs 34.8%, p=0.20), whereas patients with CKD more frequently achieved a low-density lipoprotein cholesterol target of ≤2.0 mmol/L (54.8% vs 61.3%, p0.001). Overall, only 12.5% in both groups achieved all 3 targets (12.3% vs 13.3%, p=0.33).Only 1 of 8 patients with T2D achieved optimal glycemic, BP and cholesterol targets, regardless of the presence or absence of CKD. Although more medical interventions were used in patients with CKD, a lower proportion achieved guideline-recommended targets for A1C. These findings provide a benchmark for future comparison.
- Published
- 2021
32. The Role of Combined SGLT1/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus
- Author
-
Deepak L. Bhatt, Lawrence A. Leiter, Bertram Pitt, and Gabriel Steg
- Subjects
Pharmacology ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,digestive, oral, and skin physiology ,Type 2 Diabetes Mellitus ,General Medicine ,Type 2 diabetes ,medicine.disease ,Quality of life ,Internal medicine ,Heart failure ,medicine ,Cardiology ,Pharmacology (medical) ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Stroke ,Glycemic - Abstract
Purpose In patients with type 2 diabetes mellitus (T2DM), both sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have demonstrated significant improvements in cardiovascular and kidney outcomes independent of their glycemic benefits. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings. Methods and Results Thus far, the results from SCORED and SOLOIST (trials studying the SGLT1/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding. Conclusions The role of SGLT1/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.
- Published
- 2021
33. Efficacy and Safety of Inclisiran in Patients with Polyvascular Disease: Pooled, Post Hoc Analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 Randomized Controlled Trials
- Author
-
Wolfgang Koenig, Lorena Garcia Conde, Ulf Landmesser, Lawrence A. Leiter, Kausik K. Ray, Gregory G. Schwartz, R Scott Wright, Jackie Han, and Frederick J. Raal
- Subjects
Pharmacology ,Pharmacology (medical) ,General Medicine ,Cardiology and Cardiovascular Medicine - Abstract
Purpose Patients with polyvascular disease (PVD) are at very high cardiovascular risk and require intensive lipid-lowering therapy. This analysis describes the lipid-lowering efficacy and safety of inclisiran versus placebo in patients with and without PVD. Methods In this post hoc analysis of the ORION-9, ORION-10, and ORION-11 trials, patients were randomized 1:1 to receive 284 mg inclisiran (300 mg inclisiran sodium) or placebo on day 1, day 90, and 6-monthly thereafter. Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to day 510 and corresponding time-adjusted change from day 90 and up to day 540 were evaluated per patients’ PVD status. Safety was assessed over 540 days. Results Of 3454 patients, 470 (13.6%) had PVD, and 2984 (86.4%) did not. Baseline characteristics were generally balanced between the treatment arms in both cohorts. A greater proportion of patients with PVD had comorbidities versus those without. The mean (95% confidence interval [CI]) placebo-corrected LDL-C percentage change from baseline to day 510 was −48.9% (−55.6 to −42.2) in patients with PVD and −51.5% (−53.9 to −49.1) in patients without. Proportions of patients with reported treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events were similar between treatment arms, irrespective of PVD status, except for an excess of mild or moderate clinically relevant TEAEs at the injection site with inclisiran. Conclusion Twice-yearly inclisiran dosing (after the initial and 3-month doses) was well tolerated and provided effective and sustained lipid-lowering in patients, irrespective of PVD status.
- Published
- 2022
34. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk
- Author
-
Aruna, Das Pradhan, Robert J, Glynn, Jean-Charles, Fruchart, Jean G, MacFadyen, Elaine S, Zaharris, Brendan M, Everett, Stuart E, Campbell, Ryu, Oshima, Pierre, Amarenco, Dirk J, Blom, Eliot A, Brinton, Robert H, Eckel, Marshall B, Elam, João S, Felicio, Henry N, Ginsberg, Assen, Goudev, Shun, Ishibashi, Jacob, Joseph, Tatsuhiko, Kodama, Wolfgang, Koenig, Lawrence A, Leiter, Alberto J, Lorenzatti, Boris, Mankovsky, Nikolaus, Marx, Børge G, Nordestgaard, Dénes, Páll, Kausik K, Ray, Raul D, Santos, Handrean, Soran, Andrey, Susekov, Michal, Tendera, Koutaro, Yokote, Nina P, Paynter, Julie E, Buring, Peter, Libby, Paul M, Ridker, and Maureen, McClelland
- Subjects
Hypertriglyceridemia ,Apolipoprotein C-III ,Cholesterol, HDL ,Hyperlipidemias ,General Medicine ,Cholesterol, LDL ,Cholesterol ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Risk Factors ,PROMINENT Investigators ,General & Internal Medicine ,Humans ,PPAR alpha ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,11 Medical and Health Sciences ,Triglycerides ,Hypolipidemic Agents - Abstract
Background High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. Methods In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. Results Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. Conclusions Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.)
- Published
- 2022
35. Impact of kidney function on the safety and efficacy of insulin degludec versus insulin glargine <scp>U300</scp> in people with type 2 diabetes: A post hoc analysis of the <scp>CONCLUDE</scp> trial
- Author
-
Kamlesh Khunti, Thomas R. Pieber, Steen Ladelund, David C. Klonoff, Lawrence A. Leiter, Simon Heller, Harpreet S. Bajaj, Athena Philis-Tsimikas, Ting Jia, and Lily Wagner
- Subjects
Blood Glucose ,Glycated Hemoglobin ,Insulin degludec ,Oncology ,medicine.medical_specialty ,Insulin glargine ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin Glargine ,Renal function ,Type 2 diabetes ,Kidney ,medicine.disease ,Insulin, Long-Acting ,Endocrinology ,Diabetes Mellitus, Type 2 ,Internal medicine ,Post-hoc analysis ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,business ,medicine.drug - Published
- 2021
36. Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial
- Author
-
Rafael Diaz, Stephen D. Wiviott, Marc S. Sabatine, Jindřich Špinar, Itamar Raz, Assen Goudev, Ofri Mosenzon, Deepak L. Bhatt, Avivit Cahn, Ingrid Gause-Nilsson, Kyong-Soo Park, Darren K. McGuire, Kazuma Oyama, Sabina A. Murphy, Lawrence A. Leiter, John P.H. Wilding, and Julia F Kuder
- Subjects
medicine.medical_specialty ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Overweight ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,Internal medicine ,medicine ,Humans ,Obesity ,Benzhydryl Compounds ,Dapagliflozin ,Sodium-Glucose Transporter 2 Inhibitors ,Heart Failure ,2. Zero hunger ,business.industry ,Hazard ratio ,Absolute risk reduction ,Atrial fibrillation ,medicine.disease ,3. Good health ,Diabetes Mellitus, Type 2 ,chemistry ,Relative risk ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Body mass index - Abstract
Aims We investigated the associations between obesity, cardiorenal events, and benefits of dapagliflozin in patients with type 2 diabetes mellitus (T2DM). Methods and results DECLARE–TIMI 58 randomized patients with T2DM and either atherosclerotic cardiovascular (CV) disease or multiple risk factors to dapagliflozin vs. placebo. Patients were stratified by body mass index (BMI, kg/m2): normal (18.5 to Conclusions In DECLARE–TIMI 58, patients with T2DM and higher BMI were more likely to have HHF and AF/AFL. Whereas relative risk reductions in CV and renal outcomes with dapagliflozin were generally consistent across the range of BMI, absolute risk reduction in obesity-related outcomes including HHF and AF/AFL tended to be larger in obese patients with T2DM. Clinical trial registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01730534.
- Published
- 2021
37. Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial
- Author
-
Irina Chazova, Salim Yusuf, Eva Lonn, Jackie Bosch, Gilles R. Dagenais, Alvaro Avezum, Claes Held, Lawrence A. Leiter, Khalid Yusoff, Robert G. Hart, Prem Pais, Patricio Lopez-Jaramillo, Karen Sliwa, Ron J.G. Peters, Basil S. Lewis, Peggy Gao, Kamlesh Khunti, William D. Toff, Christopher M. Reid, Jun Zhu, Masira, Cardiology, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias
- Subjects
Male ,medicine.medical_specialty ,Statin ,medicine.drug_class ,primary prevention ,Placebo ,candesartan ,Hydrochlorothiazide ,Double-Blind Method ,cardiovascular disease ,Internal medicine ,medicine ,Humans ,Rosuvastatin ,Lipoprotein ,Stroke ,Antihypertensive Agents ,Aged ,Advanced and Specialized Nursing ,Primary prevention ,Candesartan ,business.industry ,lipoprotein ,Hazard ratio ,statin ,blood pressure ,Middle Aged ,Cardiovascular disease ,medicine.disease ,Blood pressure ,Cardiology ,Drug Therapy, Combination ,Female ,Neurology (clinical) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,medicine.drug - Abstract
Digital, Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]). Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated., Correction to: Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial, Ciencias Médicas y de la Salud
- Published
- 2021
38. Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials
- Author
-
Vivian L Choo, Danielle Lee, Tauseef Khan, Sonia Blanco Mejia, Thomas M.S. Wolever, David J.A. Jenkins, Laura Chiavaroli, Cyril W.C. Kendall, Andreea Zurbau, Russell J. de Souza, Annette Cheung, Lawrence A. Leiter, Amna Ahmed, Fei Au-Yeung, John L. Sievenpiper, Qi Liu, and Sabrina Ayoub-Charette
- Subjects
Calorie ,Dried fruit ,Medicine (miscellaneous) ,Fructose ,030204 cardiovascular system & hematology ,Cochrane Library ,Beverages ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Nutritional Epidemiology ,030212 general & internal medicine ,Food science ,2. Zero hunger ,Nutrition and Dietetics ,business.industry ,Fasting ,medicine.disease ,Uric Acid ,Gout ,chemistry ,Fruit ,Meta-analysis ,Uric acid ,Fruit juice ,Sugars ,business - Abstract
Background Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. Objectives To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. Methods MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. Results We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL; 95% CI: 0.06-0.27 mg/dL; P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. Conclusions Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.
- Published
- 2021
39. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial
- Author
-
Kausik K Ray, Roel P T Troquay, Frank L J Visseren, Lawrence A Leiter, R Scott Wright, Sheikh Vikarunnessa, Zsolt Talloczy, Xiao Zang, Pierre Maheux, Anastasia Lesogor, and Ulf Landmesser
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
Whether long-term treatment with the twice-yearly, siRNA therapeutic inclisiran, which reduces hepatic production of proprotein convertase subtilisin/kexin type 9 (PCSK9), results in sustained reductions in LDL cholesterol with an acceptable safety profile is not known. The aim of this study was to assess the effect of long-term dosing of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol.ORION-3 was a 4-year open-label extension study of the placebo-controlled, phase 2 ORION-1 trial, conducted at 52 sites across five countries. Patients with prevalent atherosclerotic cardiovascular disease or high-risk primary prevention and elevated LDL cholesterol despite maximally tolerated statins or other LDL-lowering treatments, or with documented statin intolerance, who had completed the ORION-1 trial were eligible. Patients receiving inclisiran in ORION-1 received twice-yearly 300 mg subcutaneous inclisiran sodium throughout ORION-3 (inclisiran-only arm), whereas patients receiving placebo in ORION-1 first received subcutaneous evolocumab 140 mg every 2 weeks until day 360 thereafter transitioning to inclisiran twice-yearly for the remainder of ORION-3 study (switching arm). The primary efficacy endpoint was the percentage change in LDL cholesterol with inclisiran from the start of ORION-1 through to day 210 of the open label extension phase in the inclisiran-only arm (approximately 570 days of total inclisiran exposure in the modified intention-to-treat population). Secondary and exploratory endpoints included changes in LDL-C cholesterol and PCSK9 concentrations levels up to day 1440 (4 years) in each arm, and safety. ORION-3 is registered with ClinicalTrials.gov, NCT03060577.Of the original ORION-1 cohort of 497 patients, 290 of 370 patients allocated to drug continued into the inclisiran-only arm and 92 of 127 patients allocated to placebo entered the switching-arm in the ORION-3 extension study conducted between March 24, 2017, and Dec 17, 2021. In the inclisiran-only arm, LDL cholesterol was reduced by 47·5% (95% CI 50·7-44·3) at day 210 and sustained over 1440 days. The 4-year averaged mean reduction of LDL-C cholesterol was 44·2% (95% CI: 47·1-41·4), with reductions in PCSK9 ranging from 62·2% to 77·8%. Adverse events at the injection site were reported in 39 (14%) of 284 patients in the inclisiran-only arm and 12 (14%) of 87 patients in the switching arm. The incidence of treatment-emergent serious adverse events possibly related to the study drug was 1% (three of 284) in the inclisiran-only arm and 1% (one of 87) in the switching arm.Twice-yearly inclisiran provided sustained reductions in LDL cholesterol and PCSK9 concentrations and was well tolerated over 4 years in the extension study. This is the first prospective long-term study to assess repeat hepatic exposure to inclisiran.Novartis Pharma.
- Published
- 2022
40. A novel kidney disease index reflecting both the albumin-to-creatinine ratio and estimated glomerular filtration rate, predicted cardiovascular and kidney outcomes in type 2 diabetes
- Author
-
Hertzel C, Gerstein, Chinthanie, Ramasundarahettige, Alvero, Avezum, Jan, Basile, Ignacio, Conget, William C, Cushman, Gilles R, Dagenais, Edward, Franek, Mark, Lakshmanan, Fernando, Lanas, Lawrence A, Leiter, Nana, Pogosova, Jeffrey, Probstfield, Peter J, Raubenheimer, Matthew, Riddle, Jonathan, Shaw, Wayne H-H, Sheu, Theodora, Temelkova-Kurktschiev, Ibrahim, Turfanda, and Denis, Xavier
- Subjects
Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Risk Factors ,Albumins ,Creatinine ,Endocrinology, Diabetes and Metabolism ,Albuminuria ,Humans ,Kidney Diseases ,Kidney ,Cardiology and Cardiovascular Medicine ,Glomerular Filtration Rate - Abstract
Background The estimated glomerular filtration rate (eGFR) and the albumin-to-creatinine ratio (ACR) are risk factors for diabetes-related outcomes. A composite that captures information from both may provide a simpler way of assessing risk. Methods 9115 of 9901 Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) participants with both an ACR and eGFR at baseline were included in this post hoc epidemiologic analysis. The hazard of higher baseline levels of 1/eGFR and natural log transformed ACR (calculated as ln [ACR × 100] to eliminate negative values) and their interaction for incident major adverse cardiovascular events (MACE), kidney outcomes, and deaths was estimated. The hazard of the geometric mean of these two baseline measures (the kidney disease index or KDI) was also assessed. Results A non-linear relationship was observed between 1/eGFR and all three outcomes, and between ln [ACR × 100] and the kidney outcome. There was also a negative interaction between these two risk factors with respect to MACE and death. Conversely, a linear relationship was noted between the KDI and all three outcomes. People in the highest KDI fifth experienced the highest incidence of MACE, death, and the kidney outcome (4.43, 4.56, and 5.55/100 person-years respectively). C statistics for the KDI were similar to those for eGFR and albuminuria. Conclusions The KDI combines the baseline eGFR and ACR into a novel composite risk factor that has a simple linear relationship with incident serious outcomes in people with diabetes and additional CV risk factors. Trial Registration clinicaltrials.gov NCT01394952.
- Published
- 2022
41. Efficacy and safety of inclisiran in patients with cerebrovascular disease: ORION-9, ORION-10, and ORION-11
- Author
-
Wolfgang Koenig, Kausik K. Ray, Ulf Landmesser, Lawrence A. Leiter, Gregory G. Schwartz, R. Scott Wright, Lorena Garcia Conde, Jackie Han, and Frederick J. Raal
- Subjects
General Medicine - Published
- 2023
42. Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes A Prespecified Secondary Analysis of a Randomized Clinical Trial
- Author
-
Darren K. McGuire, John P.H. Wilding, Marc S. Sabatine, Avivit Cahn, Thomas A Zelniker, Hiddo J. Lambers Heerspink, Lawrence A. Leiter, KyungAh Im, Itamar Raz, Deepak L. Bhatt, Erica L. Goodrich, Stephen D. Wiviott, Jamie P. Dwyer, Anna Maria Langkilde, Ofri Mosenzon, Ingrid Gause-Nilsson, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
- Subjects
Male ,medicine.medical_specialty ,Urology ,Renal function ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Placebo ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,medicine ,Albuminuria ,Humans ,030212 general & internal medicine ,Dapagliflozin ,Benzhydryl Compounds ,Renal Insufficiency, Chronic ,Sodium-Glucose Transporter 2 Inhibitors ,Aged ,Original Investigation ,Heart Failure ,Creatinine ,business.industry ,Middle Aged ,medicine.disease ,Treatment Outcome ,chemistry ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Relative risk ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Kidney disease ,Glomerular Filtration Rate - Abstract
ImportanceSodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown.ObjectiveTo assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).Design, setting, and participantsThis secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (InterventionsDapagliflozin vs placebo.Main outcomes and measuresThe dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF.ResultsAt baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher.Conclusions and relevanceThe effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria.Trial registrationClinicalTrials.gov Identifier: NCT01730534.
- Published
- 2021
43. Relation of change or substitution of low-and no-calorie sweetened beverages with cardiometabolic outcomes: A systematic review and meta-analysis of prospective cohort studies
- Author
-
John L. Sievenpiper, Cyril W. C. Kendall, Jordi Salas-Salvadó, Hana Kahleová, Dario Rahelić, Per Bendix Jeppesen, Lawrence A. Leiter, James O. Hill, Vasanti S. Malik, Nema McGlynn, Tauseef A. Khan, and Jennifer J. Lee
- Abstract
Background: Adverse associations of low-and no-calorie sweetened beverages (LNCSBs) with cardiometabolic outcomes in observational studies may be explained by reverse causality and residual confounding. Purpose: To address these limitations we used change analyses of repeated measures of intake and substitution analyses to synthesize the association of LNCSBs with cardiometabolic outcomes. Study Selection: MEDLINE, EMBASE, and the Cochrane Library were searched up to 10 June 2021 for prospective cohort studies ≥1-year follow-up duration in adults. Outcomes included changes in clinical measures of adiposity, risk of overweight/obesity, metabolic syndrome, diabetes, cardiovascular disease, and total mortality. Data Extraction: Two independent reviewers extracted data, assessed study quality, and certainty of evidence using GRADE. Data was pooled using random-effects model and expressed as mean difference (MD) or risk ratio (RR) and 95% CI. Data Synthesis: Fourteen cohorts (416,830 participants) met the eligibility criteria. Change in LNCSB intake was associated with lower weight (5 cohorts, 136,206 participants; MD, -0.008 [95% CI: -0.014, -0.002] kg/y). Substitution of LNCSBs for sugar-sweetened beverages (SSBs) was associated with lower weight (3 cohorts, 165,579 participants; MD, -0.12 [95% CI: -0.14, -0.01] kg/y) and lower incidence of obesity (1 cohort, 15,765 participants; RR, 0.88 [0.88, 0.89]), coronary heart disease (6 cohorts, 233,676 participants; RR, 0.89 [95% CI: 0.81, 0.98]), CVD mortality (1 cohort, 118,363 participants; RR, 0.95 [95% CI: 0.90, 0.99]), and total mortality (1 cohort, 118,363 participants; RR, 0.96 [95% CI: 0.94, 0.98]) with no adverse associations across other outcomes. Substitution of water for SSBs showed lower weight (3 cohorts, 165,579 participants; MD, -0.10 [95% CI: -0.13, -0.06] kg/y), lower waist circumference (1 cohort, 173 participants; MD, -2.71[95% CI: -4.27, -1.15] cm/y) and percent body fat (1 cohort, 173 participants; MD, -1.51 [95% CI: -2.61, -0.42] %/y), and lower incidence of obesity (1 cohort, 15,765 participants; RR, 0.85 [95% CI: 0.75, 0.97]) and diabetes (3 cohorts, 281,855 participants; RR, 0.96 [95% CI: 95% CI: 0.94, 0.98]). Substitution of LNCSBs for water showed no adverse associations. Limitations: The evidence was low to very low certainty owing downgrades for imprecision, indirectness and/or inconsistency. Conclusions: LNCSBs were not associated with cardiometabolic harm in analyses that model the exposure as change or substitutions. The available evidence provides some indication that LNCSBs in their intended substitution for SSBs may be associated with cardiometabolic benefit, comparable to the standard of care, water.
- Published
- 2022
44. Icosapent ethyl for reduction of persistent cardiovascular risk: a critical review of major medical society guidelines and statements
- Author
-
Michael Miller, Lale Tokgozoglu, Klaus G. Parhofer, Yehuda Handelsman, Lawrence A. Leiter, Ulf Landmesser, Eliot A. Brinton, and Alberico L. Catapano
- Subjects
Hypertriglyceridemia ,General Medicine ,Cholesterol ,Eicosapentaenoic Acid ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Risk Factors ,Fatty Acids, Omega-3 ,Internal Medicine ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,Societies, Medical ,Triglycerides - Abstract
REDUCE-IT demonstrated that adding 4 g/day of icosapent ethyl (IPE; purified ethyl ester of eicosapentaenoic acid [EPA]) to statins substantially reduced cardiovascular disease (CVD) events, with few adverse effects. These data prompted numerous leading medical societies across five continents, including the American College of Cardiology, the European Society of Cardiology, and the Japanese Circulation Society, to update their guidelines or scientific/consensus statements to recommend use of IPE for primary and secondary prevention of CVD events.This review discusses the incorporation of IPE into international guidelines and scientific statements, noting areas of consensus and distinction. As background, this review also describes the CVD benefits and risks of IPE as a statin adjunct, and outlines current data regarding the potential mechanisms of CVD risk reduction by EPA (as IPE) beyond triglyceride reduction.IPE is unique among 'triglyceride-lowering' treatments in having strong CVD outcomes data and, therefore, a broad international consensus among professional medical society guidelines and statements endorsing its use for CVD risk reduction in patients generally meeting REDUCE-IT inclusion criteria. IPE should be considered for CVD prevention as a statin adjunct in all such patients.Plain Language SummaryCardiovascular disease (CVD) remains the leading cause of death worldwide. Statin monotherapy is conventionally used first-line to reduce the risk of CV events, such as heart attacks and strokes, in patients with elevated cholesterol. However, considerable risk remains despite appropriate control of cholesterol levels with a statin. Consequently, research has focused on treatment of additional therapeutic targets to reduce this remaining CV risk. One such target is elevated blood triglyceride levels. Unfortunately, most drugs that lower triglyceride levels, such as niacin, fibrates, and mixed omega-3 fatty acids, have not reduced the risk of cardiovascular events in clinical trials when added to statin therapy. However, the omega-3 fatty acid eicosapentaenoic acid ('EPA') administered in highly purified form as icosapent ethyl (IPE) has emerged as the first omega-3 fatty acid, and the first triglyceride-lowering agent to prevent CV events when added to statins. This was demonstrated most notably in the pivotal REDUCE-IT trial, in which IPE reduced the risk of major CV events by 25% in high-risk patients with mildly to moderately elevated triglyceride levels despite statin-controlled cholesterol levels. The mechanisms responsible for this reduction in CV events appear to go far beyond lowering triglyceride levels alone. In light of the positive results from the REDUCE-IT trial, IPE was approved for CV disease risk reduction globally, including in the United States, Canada, European Union, and the United Kingdom, and its use is being increasingly endorsed in United States and international statements and guidelines for managing CV risk. Despite minor differences among guidelines, there is strong consensus that IPE should be considered for use in CVD prevention in all patients who meet the proposed criteria.
- Published
- 2022
45. Epidemiology of the diabetes-cardio-renal spectrum
- Author
-
Meir Schechter, Cheli Melzer Cohen, Ilan Yanuv, Aliza Rozenberg, Gabriel Chodick, Johan Bodegård, Lawrence A. Leiter, Subodh Verma, Hiddo J. Lambers Heerspink, Avraham Karasik, Ofri Mosenzon, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)
- Subjects
Adult ,Male ,Heart Failure ,OUTCOMES ,Epidemiology ,Endocrinology, Diabetes and Metabolism ,Type-2 Diabetes ,MORTALITY ,Middle Aged ,Kidney ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Diabetes-cardio-renal Spectrum ,Chronic Kidney Disease ,SURVIVAL ,Humans ,HEART-FAILURE ,Female ,Cross-sectional Study ,Renal Insufficiency ,Renal Insufficiency, Chronic ,Cardiology and Cardiovascular Medicine ,Aged ,Glomerular Filtration Rate - Abstract
Background Type-2 diabetes (T2D), chronic kidney disease, and heart failure (HF) share epidemiological and pathophysiological features. Although their prevalence was described, there is limited contemporary, high-resolution, epidemiological data regarding the overlap among them. We aimed to describe the epidemiological intersections between T2D, HF, and kidney dysfunction in an entire database, overall and by age and sex. Methods This is a cross-sectional analysis of adults ≥ 25 years, registered in 2019 at Maccabi Healthcare Services, a large healthcare maintenance organization in Israel. Collected data included sex, age, presence of T2D or HF, and last estimated glomerular filtration rate (eGFR) in the past two years. Subjects with T2D, HF, or eGFR 2 were defined as within the diabetes-cardio-renal (DCR) spectrum. Results Overall, 1,389,604 subjects (52.2% females) were included; 445,477 (32.1%) were 25– 2, and 11,605 (0.84%) with HF. Overall, 12.6% had at least one condition within the DCR spectrum, 2.0% had at least two, and 0.23% had all three. Cardiorenal syndrome (both HF and eGFR 2) was prevalent in 0.40% of the entire population and in 2.3% of those with T2D. In patients with both HF and T2D, 55.2% had eGFR 2 and 15.8% had eGFR 2. Amongst those within the DCR spectrum, T2D was prominent in younger participants, but was gradually replaced by HF and eGFR 2 with increasing age. The congruence between all three conditions increased with age. Conclusions This large, broad-based study provides a contemporary, high-resolution prevalence of the DCR spectrum and its components. The results highlight differences in dominance and degree of congruence between T2D, HF, and kidney dysfunction across ages.
- Published
- 2022
46. Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial
- Author
-
Remo H.M. Furtado, Itamar Raz, Erica L. Goodrich, Sabina A. Murphy, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Philip Aylward, Anthony J Dalby, Mikael Dellborg, Doina Dimulescu, José C. Nicolau, Anthonius J.M. Oude Ophuis, Avivit Cahn, Ofri Mosenzon, Ingrid Gause-Nilsson, Anna Maria Langkilde, Marc S. Sabatine, and Stephen D. Wiviott
- Subjects
Heart Failure ,Male ,Myocardial Infarction ,Blood Pressure ,Acute Kidney Injury ,Middle Aged ,Diabetes Mellitus, Type 2 ,Glucosides ,Physiology (medical) ,Humans ,Female ,Benzhydryl Compounds ,Cardiology and Cardiovascular Medicine ,Sodium-Glucose Transporter 2 Inhibitors ,Aged - Abstract
Background: Dapagliflozin improved heart failure and kidney outcomes in patients with type 2 diabetes (T2DM) with or at high risk for atherosclerotic cardiovascular disease in the DECLARE-TIMI 58 trial (Dapagliflozin Effect on Cardiovascular Events – Thrombolysis in Myocardial Infarction 58). Here, the aim was to analyze the efficacy and safety of dapagliflozin stratified according to baseline systolic blood pressure (SBP). Methods: The DECLARE-TIMI 58 trial randomly assigned patients with T2DM and either previous atherosclerotic cardiovascular disease or atherosclerotic cardiovascular disease risk factors to dapagliflozin or placebo. Patients were categorized by baseline SBP levels: Results: The trial comprised 17 160 patients; mean age, 64.0±6.8 years; 37.4% women; median duration of T2DM, 11 years; 40.6% with prevalent cardiovascular disease. Overall, dapagliflozin reduced SBP by 2.4 mm Hg (95% CI, 1.9–2.9; P P interactions =0.28 and 0.52, respectively). Among normotensive patients, the hazard ratios were 0.66 (95% CI, 0.42–1.05) and 0.39 (95% CI, 0.19–0.78), respectively, for hospitalization for heart failure and the renal-specific outcome. Events of volume depletion, amputation, and acute kidney injury did not differ with dapagliflozin overall or within any baseline SBP group. Conclusions: In patients with T2DM with or at high atherosclerotic cardiovascular disease risk, dapagliflozin reduced risk for hospitalization for heart failure and renal outcomes regardless of baseline SBP, with no difference in adverse events of interest at any level of baseline SBP. These results indicate that dapagliflozin provides cardiorenal benefits in patients with T2DM at high atherosclerotic cardiovascular disease risk independent of baseline blood pressure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.
- Published
- 2022
47. Lixilan ONE CAN: Randomisierte Studie zum Vergleich eines täglichen vs. wöchentlichen Titrationsalgorithmus für den Wechsel von Basalinsulin zur Fixkombination iGlarLixi bei Typ-2-Diabetespatienten in Kanada
- Author
-
Irene Hramiak, Hertzel C. Gerstein, Thorsten Siegmund, Lawrence A. Leiter, Jean-François Yale, Harpreet Bajaj, John Stewart, Marie-Josée Toutounji, and Stewart B. Harris
- Published
- 2022
48. Causes and Risk Factors for Death in Diabetes
- Author
-
Benjamin M. Scirica, Darren K. McGuire, Deepak L. Bhatt, Eugene Braunwald, KyungAh Im, Itamar Raz, Ilaria Cavallari, Ph. Gabriel Steg, Lawrence A. Leiter, and Ofri Mosenzon
- Subjects
medicine.medical_specialty ,business.industry ,Diabetes mellitus ,Internal medicine ,medicine ,MEDLINE ,Cardiology and Cardiovascular Medicine ,medicine.disease ,Competing risks ,business ,TIMI - Published
- 2021
49. Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial
- Author
-
Hertzel C. Gerstein, Edward Franek, Oralee J. Varnado, Manige Konig, Lawrence A. Leiter, Sohini Raha, Denis Xavier, William C. Cushman, Matthew C. Riddle, Charles Atisso, Peter J Raubenheimer, and Mark Lakshmanan
- Subjects
Male ,Aging ,medicine.medical_specialty ,Recombinant Fusion Proteins ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Glucagon-Like Peptides ,Context (language use) ,Subgroup analysis ,Placebo ,Severity of Illness Index ,Biochemistry ,Endocrinology ,Commentaries ,Internal medicine ,dulaglutide ,Post-hoc analysis ,Cardiac conduction ,older ,medicine ,Humans ,Hypoglycemic Agents ,Online Only Articles ,Aged ,Aged, 80 and over ,business.industry ,cardiovascular ,Biochemistry (medical) ,Age Factors ,Middle Aged ,Hypoglycemia ,Immunoglobulin Fc Fragments ,Discontinuation ,Hospitalization ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Drug Therapy, Combination ,Female ,Dulaglutide ,business ,AcademicSubjects/MED00250 ,Mace ,medicine.drug - Abstract
Context Dulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed. Objective This work aimed to assess efficacy and safety of dulaglutide vs placebo in REWIND by age subgroups (≥ 65 and Methods A post hoc subgroup analysis of REWIND was conducted at 371 sites in 24 countries. Participants included type 2 diabetes patients aged 50 years or older with established cardiovascular (CV) disease or multiple CV risk factors, and a wide range of glycemic control. Patients were randomly assigned (1:1) to dulaglutide 1.5 mg or placebo as an add-on to country-specific standard of care. Main outcomes measures included MACE (first occurrence of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV or unknown causes). Results There were 5256 randomly assigned patients who were 65 years or older (mean = 71.0), and 4645 were younger than 65 years (mean = 60.7). Baseline characteristics were similar in randomized treatment groups. Dulaglutide treatment showed a similar reduction in the incidence (11% vs 13%) of MACE in older vs younger patients. The rate of permanent study drug discontinuation, incidence of all-cause mortality, hospitalizations for heart failure, severe hypoglycemia, severe renal or urinary events, and serious gastrointestinal events were similar between randomized treatment groups within each age subgroup. The incidence rate of serious cardiac conduction disorders was numerically higher in the dulaglutide group compared to placebo within each age subgroup but the difference was not statistically significant. Conclusion Dulaglutide had similar efficacy and safety in REWIND in patients65 years and older and those younger than 65 years.
- Published
- 2021
50. POOLED SAFETY ANALYSIS OF INCLISIRAN IN 3,576 PATIENTS WITH APPROXIMATELY 10,000 PERSON YEARS OF EXPOSURE FROM 7 TRIALS
- Author
-
R. Scott Wright, Wolfgang Koenig, Ulf Landmesser, Lawrence A. Leiter, Anastasia Lesogor, Pierre Maheux, Frederick J. Raal, Gregory G. Schwartz, Christian Stratz, Xiao Zang, and Kausik Kumar Ray
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2023
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.