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Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown. These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status. SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular death. Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score was a prespecified secondary endpoint. This analysis evaluated change in the KCCQ-12 score from baseline to month 4. Of 1,222 patients randomized, 1,113 (91%) had complete KCCQ-12 data at baseline and 4 months. The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups. Sotagliflozin vs placebo reduced the risk of the primary endpoint consistently across KCCQ-12 tertiles (P trend = 0.54). Sotagliflozin-treated patients vs those receiving placebo experienced modest improvement in KCCQ-12 at 4 months (adjusted mean change: 4.1 points; 95% CI: 1.3-7.0 points; P = 0.005). KCCQ-12 improvements were consistent across prespecified subgroups, including left ventricular ejection fraction <50% or ≥50%. More patients receiving sotagliflozin vs those receiving placebo had at least small (≥5 points) improvements in KCCQ-12 at 4 months (OR: 1.38; 95% CI: 1.06-1.80; P = 0.017). Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934) [ABSTRACT FROM AUTHOR]

Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. This study sought to determine the effect of ticagrelor on limb events. Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; P interaction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (P interaction = 0.40) or TIMI major bleeding (P interaction = 0.3239). Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795) [Display omitted] [ABSTRACT FROM AUTHOR]

Elevated lipoprotein(a) (Lp[a]) concentrations are associated with increased cardiovascular event risk even in the presence of well-controlled low-density lipoprotein cholesterol levels, but few treatments are documented to reduce this residual risk. The aim of this post hoc analysis of REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) was to explore the cardiovascular benefit of icosapent ethyl (IPE) across a range of Lp(a) levels. A total of 8,179 participants receiving statin therapy with established cardiovascular disease or age ≥50 years with diabetes and ≥1 additional risk factor, fasting triglyceride 1.69 to 5.63 mmol/L, and low-density lipoprotein cholesterol 1.06 to 2.59 mmol/L were randomized to receive 2 g twice daily of IPE or matching placebo. Relationships between continuous baseline Lp(a) mass concentration and risk for first and total (first and subsequent) major adverse cardiovascular events (MACE) were analyzed, along with the effects of IPE on first MACE among those with Lp(a) concentrations ≥50 or <50 mg/dL. Among 7,026 participants (86% of those randomized) with baseline Lp(a) assessments, the median concentration was 11.6 mg/dL (Q1-Q3: 5.0-37.4 mg/dL). Lp(a) had significant relationships with first and total MACE (P < 0.0001), while event reductions with IPE did not vary across the range of Lp(a) (interaction P > 0.10). IPE significantly reduced first MACE in subgroups with concentrations ≥50 and <50 mg/dL. Baseline Lp(a) concentration was prognostic for MACE among participants with elevated triglyceride levels receiving statin therapy. Importantly, IPE consistently reduced MACE across a range of Lp(a) levels, including among those with clinically relevant elevations. [Display omitted] [ABSTRACT FROM AUTHOR]

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A post hoc analysis of the SCORED randomized trial examined the time to clinical benefit with sotagliflozin, a medication used to treat type 2 diabetes and chronic kidney disease. The study found that sotagliflozin reduced the risk of heart failure outcomes in patients with these conditions. The analysis showed that the benefits of sotagliflozin were observed as early as 95 days after randomization and were sustained throughout the study period. The findings suggest that initiating therapy with sotagliflozin quickly may lead to meaningful improvements in heart failure outcomes. [Extracted from the article]

Survival in left-sided valvular heart disease (VHD; aortic stenosis [AS], aortic regurgitation [AR], mitral stenosis [MS], mitral regurgitation [MR]) in out-of-hospital cardiac arrest (OHCA) is unknown. We studied all cases of OHCA in the Swedish Registry for Cardiopulmonary Resuscitation. All degrees of VHD, diagnosed prior to OHCA, were included. Association between VHD and survival was studied using logistic regression, gradient boosting and Cox regression. We studied time to cardiac arrest, comorbidities, survival, and cerebral performance category (CPC) score. We included 55,615 patients; 1948 with AS (3,5%), 384 AR (0,7%), 17 MS (0,03%), and 704 with MR (1,3%). Patients with MS were not described due to low case number. Time from VHD diagnosis to cardiac arrest was 3.7 years in AS, 4.5 years in AR and 4.1 years in MR. ROSC occurred in 28% with AS, 33% with AR, 36% with MR and 35% without VHD. Survival at 30 days was 5.2%, 10.4%, 9.2%, 11.4% in AS, AR, MR and without VHD, respectively. There were no survivors in people with AS presenting with asystole or PEA. CPC scores did not differ in those with VHD compared with no VHD. Odds ratio (OR) for MR and AR showed no difference in survival, while AS displayed OR 0.58 (95% CI 0.46–0.72), vs no VHD. AS is associated with halved survival in OHCA, while AR and MR do not affect survival. Survivors with AS have neurological outcomes comparable to patients without VHD. [ABSTRACT FROM AUTHOR]

The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease. We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels. We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models. We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58). In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c. [Display omitted] [ABSTRACT FROM AUTHOR]

Survival in left-sided valvular heart disease (VHD; aortic stenosis [AS], aortic regurgitation [AR], mitral stenosis [MS], mitral regurgitation [MR]) in out-of-hospital cardiac arrest (OHCA) is unknown. We studied all cases of OHCA in the Swedish Registry for Cardiopulmonary Resuscitation. All degrees of VHD, diagnosed prior to OHCA, were included. Association between VHD and survival was studied using logistic regression, gradient boosting and Cox regression. We studied time to cardiac arrest, comorbidities, survival, and cerebral performance category (CPC) score. We included 55,615 patients; 1948 with AS (3,5%), 384 AR (0,7%), 17 MS (0,03%), and 704 with MR (1,3%). Patients with MS were not described due to low case number. Time from VHD diagnosis to cardiac arrest was 3.7 years in AS, 4.5 years in AR and 4.1 years in MR. ROSC occurred in 28% with AS, 33% with AR, 36% with MR and 35% without VHD. Survival at 30 days was 5.2%, 10.4%, 9.2%, 11.4% in AS, AR, MR and without VHD, respectively. There were no survivors in people with AS presenting with asystole or PEA. CPC scores did not differ in those with VHD compared with no VHD. Odds ratio (OR) for MR and AR showed no difference in survival, while AS displayed OR 0.58 (95% CI 0.46–0.72), vs no VHD. AS is associated with halved survival in OHCA, while AR and MR do not affect survival. Survivors with AS have neurological outcomes comparable to patients without VHD. [ABSTRACT FROM AUTHOR]

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Keywords: cardiovascular risk reduction; icosapent ethyl; REDUCE-IT; type 2 diabetes; VERTIS CV EN cardiovascular risk reduction icosapent ethyl REDUCE-IT type 2 diabetes VERTIS CV 1398 1402 5 04/04/23 20230501 NES 230501 BACKGROUND Cardiovascular (CV) disease is the leading cause of morbidity and mortality for people with type 2 diabetes (T2D).[[1]] Accordingly, CV risk reduction is a key component of the standard of care for T2D, with professional society treatment recommendations endorsing a multifactorial approach that simultaneously targets individual atherosclerotic CV disease (ASCVD) risk factors.[[1], [3]] These risk factors include obesity, physical inactivity, smoking, hypertension, hyperglycaemia, insulin resistance/hyperinsulinaemia and dyslipidaemia.[[1], [3]] With regards to lipids, statins are the mainstay for ASCVD risk reduction for people with T2D, but even when low-density lipoprotein cholesterol (LDL-C) levels are controlled, residual ASCVD risk remains.[[5]] Results from the REDUCE-IT trial demonstrated that icosapent ethyl (IPE) decreased the risk of ischaemic events, including CV death, in a population with established ASCVD or with diabetes plus other ASCVD risk factors, whose LDL-C levels on statin treatment were 41-100 mg/dl with elevated fasting triglyceride (TG) levels (135-499 mg/dl).[7] The prevalence of these criteria in populations with T2D and ASCVD is not well documented. These data show that 29.6% of participants in VERTIS CV would be eligible for IPE therapy based on the REDUCE-IT trial inclusion criteria. The REDUCE-IT trial inclusion criteria were met by 29.6% of the overall VERTIS CV population at baseline, with a further 30.3% not meeting the full REDUCE-IT criteria but having baseline TG >135 mg/dl (Figure 1). [Extracted from the article]

Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, when people are treated with intensive statin therapy, the relative contributions of inflammation and hyperlipidaemia to the risk of future cardiovascular events might change, which has implications for the choice of adjunctive cardiovascular therapeutics. We aimed to evaluate the relative importance of high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) as determinants of risk for major adverse cardiovascular events, cardiovascular death, and all-cause-death among patients receiving statins. We did a collaborative analysis of patients with—or at high risk of—atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Quartiles of increasing baseline high-sensitivity CRP (a biomarker of residual inflammatory risk) and of increasing baseline LDLC (a biomarker of residual cholesterol risk) were assessed as predictors of future major adverse cardiovascular events, cardiovascular death, and all-cause death. Hazard ratios (HRs) for cardiovascular events and deaths were calculated across quartiles of high-sensitivity CRP and LDLC in analyses adjusted for age, gender, BMI, smoking status, blood pressure, previous history of cardiovascular disease, and randomised treatment group assignment. 31 245 patients were included in the analysis from the PROMINENT (n=9988), REDUCE-IT (n=8179), and STRENGTH (n=13 078) trials. The observed ranges for baseline high-sensitivity CRP and LDLC, and the relationships of each biomarker to subsequent cardiovascular event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (highest high-sensitivity CRP quartile vs lowest high-sensitivity CRP quartile, adjusted HR 1·31, 95% CI 1·20–1·43; p<0·0001), cardiovascular mortality (2·68, 2·22–3·23; p<0·0001), and all-cause mortality (2·42, 2·12–2·77; p<0·0001). By contrast, the relationship of residual cholesterol risk was neutral for major adverse cardiovascular events (highest LDLC quartile vs lowest LDLC quartile, adjusted HR 1·07, 95% CI 0·98–1·17; p=0·11), and of low magnitude for cardiovascular death (1·27, 1·07–1·50; p=0·0086) and all-cause death (1·16, 1·03–1·32; p=0·025). Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDLC. These data have implications for the selection of adjunctive treatments beyond statin therapy and suggest that combined use of aggressive lipid-lowering and inflammation-inhibiting therapies might be needed to further reduce atherosclerotic risk. Kowa Research Institute, Amarin, AstraZeneca. [ABSTRACT FROM AUTHOR]

Although ventilation imaging should be routinely performed to ensure that observed perfusion defects are not attributable to ventilation defects, the absence of significant structural lung disease on computed tomography angiography is reassuring against a ventilation abnormality. Breast neoplasms, cough, diabetes mellitus, type 2, dyspnea, hypertension, pulmonary, tricuspid valve insufficiency, thrombotic microangiopathies Computed tomography pulmonary angiography demonstrated dilation of the main pulmonary artery (asterisk), measuring 3.3 cm before its bifurcation (A), interventricular septal flattening with subtle leftward inversion (arrow), consistent with right ventricular strain (B), and diffuse vertebral osteosclerosis and signal heterogeneity, consistent with osteoblastic metastases (C). 99mTc lung perfusion scintigraphy disclosed multiple peripheral perfusion defects (arrows) in the background of otherwise heterogeneous perfusion bilaterally (D). Keywords: breast neoplasms; cough; diabetes mellitus; type 2; dyspnea; hypertension; pulmonary; thrombotic microangiopathies; tricuspid valve insufficiency EN breast neoplasms cough diabetes mellitus type 2 dyspnea hypertension pulmonary thrombotic microangiopathies tricuspid valve insufficiency 688 693 6 02/24/23 20230221 NES 230221 I Information about a real patient is presented in stages (boldface type) to an expert clinician (Dr Scirica), who responds to the information, sharing his reasoning with the reader (regular type). [Extracted from the article]

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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.clinicaltrials.gov identifier: NCT01991795 • Over 25% of patients with diabetes and stable CAD would have been eligible for THEMIS and THEMIS-PCI. • In REACH, over 50% of the patients with CAD and diabetes had a prior ischemic event. • REACH-like had higher event rates and may derive a greater absolute benefit from ticagrelor than those in THEMIS. [ABSTRACT FROM AUTHOR]

Background: The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results.Methods: SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18-80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261.Findings: From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was -26·4 mm Hg (SD 25·9) in the renal artery denervation group and -5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference -22·1 mm Hg [95% CI -27·2 to -17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was -15·6 mm Hg (SD 20·8) in the renal artery denervation group and -0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference -16·5 mm Hg [95% CI -20·5 to -12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group.Interpretation: This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control.Funding: Medtronic. [ABSTRACT FROM AUTHOR]

Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29–2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14–3.40); p- interaction = 0.8. Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population. [Display omitted] [ABSTRACT FROM AUTHOR]

Importance: High lipid concentrations are a modifiable risk factor for cardiovascular disease. Little is known about how population-level lipid concentrations, as well as trends in lipid control, have changed over the past decade among US adults.Objective: To determine whether lipid concentrations and rates of lipid control changed among US adults and whether these trends differed by sex and race and ethnicity, from 2007 to 2018.Design, Setting, and Participants: Serial cross-sectional analysis of 33 040 US adults aged 20 years or older, weighted to be nationally representative, from the National Health and Nutrition Examination Surveys (2007-2008 to 2017-2018).Main Outcomes and Measures: Lipid concentrations among US adults and rates of lipid control among adults receiving statin therapy. Lipid control was defined as a total cholesterol concentration of 200 mg/dL or less.Results: The mean age of the study population was 47.4 years, and 51.4% were women; of the 33 040 participants, 12.0% were non-Hispanic Black; 10.3%, Mexican American; 6.4%, other Hispanic American; 62.7%, non-Hispanic White; and 8.5%, other race and ethnicities (including non-Hispanic Asian. Among all US adults, age-adjusted total cholesterol improved significantly in the overall population from 197 mg/dL in 2007-2008 to 189 mg/dL in 2017-2018 (difference, -8.6 mg/dL [95% CI, -12.2 to -4.9 mg/dL]; P for trend <.001), with similar patterns for men and women. Black, Mexican American, other Hispanic, and White adults experienced significant improvements in total cholesterol, but no significant change was observed for Asian adults. Among adults receiving statin therapy, age-adjusted lipid control rates did not significantly change from 78.5% in 2007-2008 to 79.5% in 2017-2018 (difference, 1.1% [95% CI, -3.7% to 5.8%]; P for trend = .27), and these patterns were similar for men and women. Across all racial and ethnic groups, only Mexican Americans experienced a significant improvement in age-adjusted lipid control (P for trend = .008). In 2015-2018, age-adjusted rates of lipid control were significantly lower for women than for men (OR, 0.54 [95% CI, 0.40 to 0.72]). In addition, when compared with White adults, rates of lipid control while taking statins were significantly lower among Black adults (OR, 0.66 [95% CI, 0.47 to 0.94]) and other Hispanic adults (OR, 0.59 [95% CI, 0.37 to 0.95]); no significant differences were observed for other racial and ethnic groups.Conclusions and Relevance: In this serial cross-sectional study, lipid concentrations improved in the US adult population from 2007-2008 through 2017-2018. These patterns were observed across all racial and ethnic subgroups, with the exception of non-Hispanic Asian adults. [ABSTRACT FROM AUTHOR]

Background: REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.Objectives: Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.Methods: We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.Results: A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.Conclusions: Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. [REDUCE-IT]; NCT01492361). [ABSTRACT FROM AUTHOR]

The National Cardiovascular Data Registry is a group of registries maintained by the American College of Cardiology Foundation. These registries are used by a diverse constituency to improve the quality and outcomes of cardiovascular care, to assess the safety and effectiveness of new therapies, and for research. To achieve these goals, registry data must be complete and reliable. In this article, we review the process of National Cardiovascular Data Registry data collection, assess data completeness and integrity, and report on the current state of the data. Registry data are complete. Accuracy is very good but variable, and there is room for improvement. Knowledge of the quality of data is essential to ensuring its appropriate use. [ABSTRACT FROM AUTHOR]

Pharmacists play a crucial role in the management of heart failure, contributing to patient-specific, facility-specific, and population services. They are key stakeholders in ensuring the optimization of guideline-directed medical therapy (GDMT) for heart failure patients, including medication selection, optimization, and adherence. Studies have shown that involving pharmacists in the care team leads to higher rates of achieving GDMT, resulting in lower mortality and hospitalization rates. However, there are challenges in embedding pharmacists in all clinical settings globally, including training, access, and scope of practice. Health institutions, clinicians, and organizations need to advocate for the inclusion of pharmacists in heart failure care and support their training and development. [Extracted from the article]

Importance: Acute coronary syndromes (ACS) are characterized by a sudden reduction in blood supply to the heart and include ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina. Each year, an estimated more than 7 million people in the world are diagnosed with ACS, including more than 1 million patients hospitalized in the US.Observations: Chest discomfort at rest is the most common presenting symptom of ACS and affects approximately 79% of men and 74% of women presenting with ACS, although approximately 40% of men and 48% of women present with nonspecific symptoms, such as dyspnea, either in isolation or, more commonly, in combination with chest pain. For patients presenting with possible ACS, electrocardiography should be performed immediately (within 10 minutes of presentation) and can distinguish between STEMI and non-ST-segment elevation ACS (NSTE-ACS). STEMI is caused by complete coronary artery occlusion and accounts for approximately 30% of ACS. ACS without significant ST-segment elevation on electrocardiography, termed NSTE-ACS, account for approximately 70% of ACS, are caused by partial or intermittent occlusion of the artery and are associated with ST-segment depressions (approximately 31%), T-wave inversions (approximately 12%), ST-segment depressions combined with T-wave inversions (16%), or neither (approximately 41%). When electrocardiography suggests STEMI, rapid reperfusion with primary percutaneous coronary intervention (PCI) within 120 minutes reduces mortality from 9% to 7%. If PCI within 120 minutes is not possible, fibrinolytic therapy with alteplase, reteplase, or tenecteplase at full dose should be administered for patients younger than 75 years without contraindications and at half dose for patients 75 years or older (or streptokinase at full dose if cost is a consideration), followed by transfer to a facility with the goal of PCI within the next 24 hours. High-sensitivity troponin measurements are the preferred test to evaluate for NSTEMI. In high-risk patients with NSTE-ACS and no contraindications, prompt invasive coronary angiography and percutaneous or surgical revascularization within 24 to 48 hours are associated with a reduction in death from 6.5% to 4.9%.Conclusions and Relevance: Each year, an estimated more than 7 million people are diagnosed with ACS worldwide. For patients with STEMI, coronary catheterization and PCI within 2 hours of presentation reduces mortality, with fibrinolytic therapy reserved for patients without access to immediate PCI. For high-risk patients with NSTE-ACS without contraindications, prompt invasive coronary angiography followed by percutaneous or surgical revascularization is associated with lower rates of death. [ABSTRACT FROM AUTHOR]

BACKGROUND Increases in lipid levels and cancers with tofacitinib prompted a trial of major adverse cardiovascular events (MACE) and cancers in patients with rheumatoid arthritis receiving tofacitinib as compared with a tumor necrosis factor (TNF) inhibitor. METHODS We conducted a randomized, open-label, noninferiority, postauthorization, safety end-point trial involving patients with active rheumatoid arthritis despite methotrexate treatment who were 50 years of age or older and had at least one additional cardiovascular risk factor. Patients were randomly assigned in a 1:1:1 ratio to receive tofacitinib at a dose of 5 mg or 10 mg twice daily or a TNF inhibitor. The coprimary end points were adjudicated MACE and cancers, excluding non-melanoma skin cancer. The noninferiority of tofacitinib would be shown if the upper boundary ofthe two-sided 95% confidence interval for the hazard ratio was less than 1.8 for the combined tofacitinib doses as compared with a TNF inhibitor. RESULTS A total of 1455 patients received tofacitinib at a dose of 5 mg twice daily, 1456 received tofacitinib at a dose of 10 mg twice daily, and 1451 received a TNF inhibitor. During a median follow-up of 4.0 years, the incidences of MACE and cancer were higher with the combined tofacitinib doses (3.4% [98 patients] and 4.2% [122 patients], respectively) than with a TNF inhibitor (2. 5% [37 patients] and 2.9% [42 patients]). The hazard ratios were 1.33 (95% confidence interval [CI], 0.91 to 1.94) for MACE and 1.48 (95% CI, 1.04 to 2.09) for cancers; the noninferiority of tofacitinib was not shown. The incidences of adjudicated opportunistic infections (including herpes zoster and tuberculosis), all herpes zoster (nonserious and serious), and adjudicated nonmelanoma skin cancer were higher with tofacitinib than with a TNF inhibitor. Efficacy was similar in all three groups, with improvements from month 2 that were sustained through trial completion. CONCLUSIONS In this trial comparing the combined tofacitinib doses with a TNF inhibitor in a cardiovascular risk-enriched population, risks of MACE and cancers were higher with tofacitinib and did not meet noninferiority criteria. Several adverse events were more common with tofacitinib. (Funded by Pfizer; ORAL Surveillance ClinicalTrials .gov number, NCT0209246Z) [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery.Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting.Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; P=0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56-0.87]; P=0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50-0.81]; P=0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%-10.2%) in first events, with a number needed to treat of 16 (95% CI, 10-44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P=0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups.Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function.Methods: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke).Results: Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min-1·1.73 m-2 (range, 17-123 mL·min-1·1.73 m-2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59-0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57-0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min-1·1.73 m-2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51-0.95]; P=0.02). Although patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86-2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90-2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76).Conclusions: In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361. [ABSTRACT FROM AUTHOR]

Background: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) randomized statin-treated patients with elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in adjudicated events, including the primary endpoint (cardiovascular [CV] death, myocardial infarction [MI], stroke, coronary revascularization, unstable angina requiring hospitalization) and key secondary endpoint (CV death, MI, stroke) with IPE.Objectives: The purpose of this study was to determine the effects of IPE on investigator-reported events.Methods: Potential endpoints were collected by blinded site investigators and subsequently adjudicated by a blinded Clinical Endpoint Committee (CEC) according to a prespecified charter. Investigator-reported events were compared with adjudicated events for concordance.Results: There was a high degree of concordance between investigator-reported and adjudicated endpoints. The simple Kappa statistic between CEC-adjudicated vs site-reported events for the primary endpoint was 0.89 and for the key secondary endpoint was 0.90. Based on investigator-reported events in 8,179 randomized patients, IPE significantly reduced the rate of the primary endpoint (19.1% vs 24.6%; HR: 0.74 [95% CI: 0.67-0.81]; P < 0.0001) and the key secondary endpoint (10.5% vs 13.6%; HR: 0.75 [95% CI: 0.66-0.85]; P < 0.0001). Among adjudicated events, IPE similarly reduced the rate of the primary and key secondary endpoints.Conclusions: IPE led to consistent, significant reductions in CV events, including MI and coronary revascularization, as determined by independent, blinded CEC adjudication as well as by blinded investigator-reported assessment. These results highlight the robust evidence for the substantial CV benefits of IPE seen in REDUCE-IT and further raise the question of whether adjudication of CV outcome trial endpoints is routinely required in blinded, placebo-controlled trials. (Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT [Reduction of Cardiovascular Events With EPA - Intervention Trial]; NCT01492361). [ABSTRACT FROM AUTHOR]

The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) trial demonstrated that high-dose icosapent-ethyl reduced the risk of ischemic events in statin-treated patients with elevated triglycerides (TG) and either atherosclerotic cardiovascular disease (ASCVD) or diabetes plus at least one risk factor. Using data from REACH (Reduction of Atherothrombosis for Continued Health), a large international registry of outpatients with or at risk of ASCVD, we evaluated the proportion of patients potentially eligible for enrolment in REDUCE-IT and compared their outcomes to those excluded because of low TG. Among 62,464 patients with either ASCVD or diabetes enrolled in the REACH Registry, 1036/8418 (12.3%) patients in primary prevention and 6049/54046 (11.2%) patients in secondary prevention (11.3% overall) would have been eligible for inclusion in REDUCE-IT. Compared with patients excluded for low TG level, adjusted risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, or coronary revascularization was higher in the REDUCE-IT eligible group (HR:1.06, 95%CI:1.00–1.13, p = 0.04). In addition, unstable angina, non-fatal MI, percutaneous coronary intervention and coronary artery bypass grafting were also more frequent in the REDUCE-IT eligible group (HR:1.17, 95%CI:1.07–1.27, p < 0.001; HR:1.25, 95%CI:1.07–1.45, p < 0.001; HR:1.42, 95%CI:1.27–1.57, p < 0.001; HR:1.43, 95%CI:1.19–1.71, p < 0.001, respectively), whereas the adjusted risk of non-fatal stroke was lower (HR:0.64, 95%CI:0.54–0.75, p < 0.001). In this large international registry of patients with or at high-risk of ASCVD, 11.3% met the REDUCE-IT trial selection criteria. REDUCE-IT eligible patients were found to be at higher risk of cardiac atherothrombotic events, but at lower risk of stroke than trial-ineligible patients with lower TG. [Display omitted] • High dose reduced the risk of ischemic events in the REDUCE-IT trial. • In the REACH registry, 11.3% of patients would have been eligible for inclusion in REDUCE-IT. • REDUCE-IT eligible patients were at higher risk of cardiac atherothrombotic events than trial-ineligible patients with low TG. • REDUCE-IT eligible patients were at lower risk of stroke than trial-ineligible patients with low TG. [ABSTRACT FROM AUTHOR]

In an analysis of 131,601 patients admitted with a diagnosis of unstable angina during a 13-year study period, the annual percentage of patients with unstable angina decreased from 15.4% in 2002 to 3.7% in 2014 ( I p i < 0.0001) [[6]]. Composite primary end points in cardiovascular outcomes trials involving type 2 diabetes patients: should unstable angina be included in the primary end point?. [Extracted from the article]

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y12 inhibitor is an established therapy for a broad spectrum of patients with cardiovascular disease. The ischemic benefit of DAPT is partially offset by its increased bleeding risk, with intracranial hemorrhage (ICH) being the most serious complication. Although uncommon (0.2%-0.3% annually), its cumulative burden can be substantial given the number of patients afflicted by cardiovascular disease worldwide. Patients with a history of stroke or transient ischemic attack harbor a particularly high risk for ICH when treated with DAPT. Prediction rules may assist clinicians when weighing the risk/benefit ratio of prescribing DAPT for patients with stroke/transient ischemic attack in the nonacute, ambulatory setting. Currently, there are no reversal agents that can rapidly and effectively reverse the effect of P2Y12 inhibitors in routine practice, although a reversal agent for ticagrelor is under clinical investigation. [ABSTRACT FROM AUTHOR]

Choosing an antiplatelet strategy in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) at high bleeding risk (HBR), undergoing post-percutaneous coronary intervention (PCI), is complex. We used a unique open-source approach (crowdsourcing) to document if practices varied across a small, global cross-section of antiplatelet prescribers in the post-PCI setting. Five-hundred and fifty-nine professionals from 70 countries (the 'crowd') completed questionnaires containing single- or multi-option and free form questions regarding antiplatelet clinical practice in post-PCI NSTE-ACS patients at HBR. A threshold of 75% defined 'agreement'. There was strong agreement favouring monotherapy with either aspirin or a P2Y 12 inhibitor following initial DAPT, within the first year (94%). No agreement was reached on the optimal duration of DAPT or choice of monotherapy: responses were in equipoise for shorter (≤3 months, 51%) or longer (≥6 months, 46%) duration, and monotherapy choice (45% aspirin; 53% P2Y 12 inhibitor). Most respondents stated use of guideline-directed tools to assess risk, although clinical judgement was preferred by 32% for assessing bleeding risk and by 46% for thrombotic risk. The crowdsourcing methodology showed potential as a tool to assess current practice and variation on a global scale and to achieve a broad demographic representation. These preliminary results indicate a high degree of variation with respect to duration of DAPT, monotherapy drug of choice following DAPT and how thrombotic and bleeding risk are assessed. Further investigations should concentrate on interrogating practice variation between key demographic groups. • Antiplatelet choice is complex in NSTE-ACS patients at high bleeding risk. • Practice is expected to vary and may deviate from guidelines. • A crowdsourcing approach was used to assess current practices. • We noted high practice variation across a global cohort of prescribers. • Crowdsourcing may be an effective tool to monitor practice variation. [ABSTRACT FROM AUTHOR]

Background: In the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) trial, sotagliflozin, a sodium-glucose cotransporter-1 and sodium-glucose cotransporter-2 inhibitor, reduced total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure relative to placebo by 33%.Objective: To determine whether sotagliflozin increased the prespecified efficacy outcome of days alive and out of the hospital (DAOH) in the SOLOIST-WHF trial.Design: Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT03521934).Setting: 306 sites in 32 countries.Participants: 1222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure.Intervention: 200 mg of sotagliflozin once daily (with a possible dose increase to 400 mg) or matching placebo.Measurements: The primary analysis included hospitalizations for any reason on the basis of investigator-reported incidence and duration of admissions after randomization. Days alive and out of the hospital and its converse (days dead and days in the hospital) were analyzed using prespecified Poisson regression models.Results: Although similar proportions of patients in the sotagliflozin and placebo groups were hospitalized at least once (38.5% vs. 41.4%), fewer patients in the sotagliflozin group were hospitalized more than once (16.3% vs. 22.1%). There were 64 and 76 deaths in the sotagliflozin and placebo groups, respectively. The DAOH rate in the sotagliflozin group was 3% higher than in the placebo group (rate ratio [RR], 1.03 [95% CI, 1.00 to 1.06]; P = 0.027). This difference was primarily driven by a reduction in the rate of days dead (RR, 0.71 [CI, 0.52 to 0.99]; P = 0.041) rather than by a reduction in the rate of days hospitalized for any cause. For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital for 3% or 2.9 more days than those in the placebo group (91.8 vs. 88.9 days); this difference reflected a 2.6-day difference in days dead (6.3 vs. 8.9 days) and a 0.3-day difference in days in the hospital (1.9 vs. 2.2 days).Limitation: Other than heart failure, the primary reason for each hospitalization was unspecified.Conclusion: Sotagliflozin increased DAOH, a metric that may provide an additional patient-centered outcome to capture the totality of disease burden. Future studies are needed to quantify the consequences of increasing DAOH in terms of health economics and patient quality of life.Primary Funding Source: Sanofi at initiation and Lexicon Pharmaceuticals at completion. [ABSTRACT FROM AUTHOR]

Background: The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).Objectives: The aim of this work was to report the effects of the combination on overall and cause-specific mortality.Methods: The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes.Results: During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months.Conclusions: The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424). [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is highly prevalent in patients with heart failure (HF) and accounts for nearly two-thirds of cases. The use of percutaneous coronary intervention (PCI) in HF patients with CAD has markedly increased and has been suggested to be associated with improved outcomes in numerous observational studies. Randomized data comparing the impact of PCI with that of coronary artery bypass graft (CABG) or contemporary guideline-directed medical therapy alone on clinical outcomes and myocardial recovery in patients with HF are lacking. The purpose of this review is to describe the available evidence regarding the impact of PCI in acute HF (in the presence and absence of an acute coronary syndrome), chronic HF with reduced ejection fraction, and HF with preserved ejection fraction. Adequately-powered randomized clinical trials examining the outcomes with PCI in these distinct HF populations are warranted. [ABSTRACT FROM AUTHOR]

Background: THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.Objectives: In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors.Methods: Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications.Results: In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications.Conclusion: Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population. [ABSTRACT FROM AUTHOR]

A growing number of patients undergoing percutaneous coronary intervention (PCI) with stent implantation also have atrial fibrillation. This poses challenges for their optimal antithrombotic management because patients with atrial fibrillation undergoing PCI require oral anticoagulation for the prevention of cardiac thromboembolism and dual antiplatelet therapy for the prevention of coronary thrombotic complications. The combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding. Over the last decade, a series of North American Consensus Statements on the Management of Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention have been reported. Since the last update in 2018, several pivotal clinical trials in the field have been published. This document provides a focused updated of the 2018 recommendations. The group recommends that in patients with atrial fibrillation undergoing PCI, a non-vitamin K antagonist oral anticoagulant is the oral anticoagulation of choice. Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should be given to all patients during the peri-PCI period (during inpatient stay, until time of discharge, up to 1 week after PCI, at the discretion of the treating physician), after which the default strategy is to stop aspirin and continue treatment with a P2Y12 inhibitor, preferably clopidogrel, in combination with a non-vitamin K antagonist oral anticoagulant (ie, double therapy). In patients at increased thrombotic risk who have an acceptable risk of bleeding, it is reasonable to continue aspirin (ie, triple therapy) for up to 1 month. Double therapy should be given for 6 to 12 months with the actual duration depending on the ischemic and bleeding risk profile of the patient, after which patients should discontinue antiplatelet therapy and receive oral anticoagulation alone. [ABSTRACT FROM AUTHOR]

BACKGROUND The efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without albuminuria have not been well studied. METHODS We conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, >7%>), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m2 of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding. RESULTS Of 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.63 to 0.88; P<0.001). The rate of deaths from cardiovascular causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.35). For the original coprimary end point of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the hazard ratio was 0.84 (95% CI, 0.72 to 0.99); for the original coprimary end point of the first occurrence of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.77 (95% CI, 0.66 to 0.91). Diarrhea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo. CONCLUSIONS In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure than placebo but was associated with adverse events. (Funded by Sanofi and Lexicon Pharmaceuticals; SCORED ClinicalTrials.gov number, NCT03315143.). [ABSTRACT FROM AUTHOR]

Background: Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations.Methods: REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL), controlled low-density lipoprotein (41-100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes.Results: A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58-0.76]; P<0.0001; number needed to treat for 4.9 years=24); similar reductions were observed in total (first and subsequent) revascularizations (negative binomial rate ratio, 0.64 [95% CI, 0.56-0.74]; P<0.0001), and across elective, urgent, and emergent revascularizations. Icosapent ethyl significantly reduced percutaneous coronary intervention (hazard ratio, 0.68 [95% CI, 0.59-0.79]; P<0.0001) and coronary artery bypass grafting (hazard ratio, 0.61 [95% CI, 0.45-0.81]; P=0.0005).Conclusions: Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non-low-density lipoprotein-lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361. [ABSTRACT FROM AUTHOR]

Fine particulate air pollution <2.5 μm in diameter (PM2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Background: Early post-percutaneous coronary intervention chest pain (EPPCP) appears to be a common clinical phenomenon. EPPCP has not been fully explained or studied in the literature despite the abundance of clinical trials on percutaneous coronary intervention (PCI). The objective of this questionnaire-based survey is to assess the current perception of EPPCP among practicing interventional cardiologists nationwide.Methods: A survey questionnaire was designed utilizing the Survey Monkey tool to address the perceptions and current practices regarding key aspects of EPPCP among interventional cardiologists. The survey was sent to the interventional cardiologists via email.Results: The survey questionnaire regarding EPPCP was provided to 2615 practicing interventional cardiologists and resulted in 623 total survey responses, with 503 of those respondents completing all eight survey questions. A total of 50.2% of the interventional cardiologists perceive that the incidence of EPPCP is 5-10%, and 57.5% consider that repeat angiography or PCI is rarely needed (1 in 1000 cases). A total of 47.1% of the participants think that EPPCP is due to transient microvascular dysfunction, while 39% perceive it as a different entity requiring a different approach. When asked about developing a standardized labeling for the phenomenon of EPPCP, 34.8% of responders indicated that they believe EPPCP should be labeled as a benign form of chest pain/angina, and 28% preferred to describe EPPCP in non-standardized terms. Among interventional cardiologists, 80% thought that the treatment of this entity is a combination of reassurance and vasodilators and, without ischemic ECG changes, medical management is appropriate.Conclusion: A total of 72% of interventional cardiologists in our survey preferred to label EPPCP as standard nomenclature to facilitate communication between healthcare providers, patients and families in a consistent way. There is a diversity of opinion regarding EPPCP, no standard nomenclature, and no guideline to standardize practice. Further large-scale prospective studies are needed to better understand the pathophysiological mechanisms, optimal management strategies, prognostic implications, and clinical reporting of EPPCP. [ABSTRACT FROM AUTHOR]