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Dual antiplatelet therapy (DAPT) is the gold standard after acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Because local and systemic ischemic complications can occur particularly in the early phase (i.e. 1-3 months) after ACS or PCI, the synergistic platelet inhibition of aspirin and a P2Y

Bicruciate-retaining (BCR) prostheses may improve satisfaction of patient undergoing total knee arthroplasty (TKA). The objective of this randomized controlled trial was to assess whether BCR prostheses provide better clinical outcomes than posterior-stabilized (PS) prostheses.This is a randomized single-blind control trial involving a total of 77 patients with knee osteoarthritis, randomly assigned to undergo TKA with a BCR or PS implant between 2015 and 2019. Mean follow-up period was 39 months. Clinical and demographic data were extracted manually from medical records. Data acquisition included patient demographics, knee range of motion, and patient-reported outcomes via KSS, KOOS, WOMAC, and SF-12 scores.A total of 38 patients were randomized to the PS group and 39 to the BCR group. At the 5-year follow-up, no statistical differences were noted for knee range of motion or patient-reported outcomes between the two groups, except for a greater knee flexion in the early follow-up period in the PS group. Five adverse events occurred in the BCR group compared to none in the PS group (p = 0.02).BCR TKA yield similar clinical and patient-reported outcomes 5 years following the intervention compared with PS TKA. The BCR TKA had more complications.I (Randomized Controlled Trial).

Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were individually proven to reduce major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients, but the relative magnitude of benefits from these two drug classes is debated. We aimed to review current available data on GLP1-RA and SGLT2i in T2DM patients and compare their efficacy and safety in this population.We systematically searched MEDLINE/PubMed, the Cochrane Library, Google Scholar, Embase, www.tctmd.com, www.clinicaltrials.gov, www.clinicaltrialresults.org, from inception to September 17, 2020 for randomized controlled trials (RCTs) comparing the effects of GLP1-RA vs SGLT2i vs optimal medical therapy (OMT) in adult T2DM patients. Three authors independently screened references and extracted data using a predefined data collection form. Outcomes were analyzed using an indirect comparison meta-analysis of aggregate study-level data. The primary combined efficacy outcome comprised cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Secondary efficacy outcomes included all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, heart failure hospitalizations (HFH), and worsening renal function (WRF).11 RCTs enrolling a total of 98572 patients were included; 56004 (57%) patients were derived from GLP1-RA RCTs and 42568 (43%) from SGLT2i RCTs. At a median follow-up of 3.0±1.3 years, compared with OMT, both GLP1-RA and SGLT2i similarly reduced the rate of the composite primary outcome (risk ratio [RR] 0.88; 95% confidence interval [95%CI] 0.83-0.93 and RR 0.88, 95%CI 0.82-0.95, respectively) with no difference between the drug classes (RR 1.00, 95%CI 0.92-1.10). Both classes similarly reduced MI rate, cardiovascular and all-cause mortality compared with OMT; stroke reduction was only observed with GLP1-RA with no difference in the indirect comparison with SGLT2i; conversely, only SGLT2i were effective in preventing HFH. Both GLP1-RA and SGLT2i were protective against WRF, with a major efficacy of SGLT2i in the indirect comparison.This meta-analysis report that GLP1-RA and SGLT2i reduced with a similar efficacy not only MACE as MI, but also cardiovascular mortality and all-cause mortality at a median 3 years follow-up. SGLT2i were more protective in HFH and WRF than GLP1RA. These new data highlight the efficacy of SGLT2i not only in HF and chronic kidney disease (CKD) but also in ischemic heart diseases (IHD), with a homogeneity among the class, whereas the results observed with GLP1-RA are heterogenous. These findings will help clinical's decisions to optimize therapeutic strategies for diabetic patients.

Aims The European Society of Cardiology (ESC) has released three consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores, and cholesterol treatment. This study aims to evaluate whether the 2021 ESC guidelines improved the eligibility of individuals for primary prevention statin therapy before their first ST-segment elevation myocardial infarction (STEMI), and for intensive lipid-lowering treatments in secondary prevention. Methods and results The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 vs. 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up low-density lipoprotein cholesterol (LDL-C) and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021 and 2019 vs. 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, P Conclusion The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first myocardial infarction. In secondary prevention, 70% of patients kept LDL-C levels above 55 mg/dL: increasing the statin dose and adding ezetimibe were the most frequently recommended therapeutic actions.

Aims The relative safety and efficacy of de-escalation, extended duration (ED) (>12-months), and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. Methods and results Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT, and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential, and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12, and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45–0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16–2.06). The net clinical benefit and rankograms also favoured DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favouring de-escalation strategy. Conclusion DAPT for three months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

The management of patients with coronary artery disease (CAD) is complex, especially after they have been discharged from hospital after an acute coronary syndrome (ACS), because each patient may have numerous healthcare providers, and follow-up after discharge may be disjointed, or even incomplete. During follow-up after ACS, few patients have treatment intensification; rather, there is actually a major tendency towards reductions in treatment intensity, to the potential detriment of outcomes. We present here guidance from a French expert panel for the optimal management of lipid-lowering therapy up to 1 year after ACS.A French expert panel provides a practical guide for the implementation of guidelines for the management of post-ACS patients in routine practice, from hospital discharge up to one year after the index event, focusing in particular on the achievement of target LDL cholesterol (LDL-C) levels. We discuss the early follow-up (up to 6 months after discharge), and review the lipid-lowering treatment strategies that should be implemented. We discuss the evidence underpinning the prescription of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as well as recent evidence about icosapent ethyl. This review should facilitate implementation of a clear and effective lipid-lowering strategy for all patients after ACS.The panel recommends early use of high-intensity statins, in combination with ezetimibe for patients with LDL-c above 100 mg/dL at baseline. PCSK9i should be rapidly added during the first 3 months in high-risk diabetic patients with residual LDL-C above 70 mg/dL (with further benefit for those with residual LDL-C above ≥100 mg/dL) despite maximal tolerated dose statin and ezetimibe, patients with recent ACS, and patients with recurrent ischemic events under optimal medical therapy, multivessel coronary disease (MVD) and/or polyvascular disease (PVD), especially symptomatic PAD diabetic patients. Concerning Icosapent Ethyl (EPA), this drug should be introduced in patients ≥45 years of age with clinical atherosclerotic cardiovascular disease (ASCVD) or already on high-intensity or maximally tolerated statin therapy or with fasting triglycerides 135-499 mg/dL (with or without ezetimibe).Lipid-lowering treatment should be introduced as early as possible to obtain a rapid and profound decrease of LDL-c from baseline, using high-intensity statins (atorvastatin or rosuvastatin) and ezetimibe in fixed combination before discharge. Then, the strategy should be rapidly intensified by adding a PCSK9 inhibitor if the patient does not reach LDL-c levels below 55 mg/dL. We advocate this intensive strategy, which has demonstrated a further reduction in ischemic events, without safety concerns, even for patients who reach very low LDL-cholesterol levels. This approach, comprising few therapeutic steps, aims to rapidly reach LDL-c goals, improve patient compliance, and is an efficient method to fight therapeutic inertia, which remains a major issue.

The continuous progress in cardiovascular (CV) risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several CV risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (GLP1 analogues, Antithrombotic agents, PCSK9 inhibitors, SGLT2 inhibitors and Immunomodulators) strategy offers a promising potential in patients with a high-residual CV risk, who are frequently encountered in daily practice, by offering an individualised and structured approach to addressing their individual risk factors. The current review summarises the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing MACE and mortality, without a compromise on safety, albeit with the need for longer follow-up data. Key Points: - Secondary prevention remains suboptimal in many CAD patients, highlighting the need for innovative prevention strategies. - The present review discusses the current evidence on efficacy of the GAPS-I strategy in reducing MACE and mortality in patients with CAD. - The GAPS-I strategy, if widely adopted, provides a promising potential to assist cardiologists in managing patients at a heightened risk for further CV events.

Physical activity (PA) is an established modifiable factor for the prevention of cardiovascular disease. Our objective was to assess the association of PA with mortality rates in a national sample of patients with diabetes.We analyzed a nationally representative sample from The National Health and Nutrition Examination Survey (NHANES, periods 2003-2004 and 2005-2006) that used Physical Activity Monitors. Individuals were matched for BMI, number of steps/ per day and age. Three groups were created: subjects with less than 5000/steps per day (low), 5000-7500/steps per day (moderate) and more than 7500/steps per day (high levels of physical activity). All-cause mortality was ascertained through December 2015.A sample of 3,072 individuals (1018 with diabetes) was analyzed. Patients with diabetes had 30% increased risk of mortality of all causes (RR: 1,298, 95% CI [1,162-1,451], p0,001), Higher levels of physical activity (7500 steps/day) provided similar relative risk for subjects with diabetes compared to their controls [RR:1,256 (95% CI 0,910-1,732)]. In a Poisson model adjusted for sex, history of previous cardiovascular event or cancer, ethnicity, Hb1ac, SBP, and total cholesterol to HDL ratio, patients with diabetes and moderate or high PA had an associated 44% to 80% lower risk of all-cause mortality compared to those with low PA.The subgroup of patients with diabetes and high PA had no excess of mortality compared to the general population. PA can reduce the gap for all-cause mortality, used as an index of cardiovascular fitness and a clinical tool for the assessment of mortality risk.

Although some observational studies suggest a potential association of low levels of low-density lipoprotein cholesterol (LDL-C) with intracerebral haemorrhage (ICH), these analyses have issues of confounding where other factors (e.g. older age, frailty) that likely explain the findings, and the number of events was very low. More recent results from randomized clinical trials have not found an increased risk in ICH, most notably trials using PCSK9 inhibitors that achieve very low levels of LDL-C, but also in the long-term follow-up of the IMPROVE-IT trial. Also, other statin-associated safety issues, including new onset diabetes and the cancer risk should not be the reason of statin discontinuation, especially for the former, the benefits highly outweigh the risk (even 5×), and for the latter, there is no confirmed link suggesting any increased risk, in opposite, data exist suggesting benefits of statin therapy in cancer prevention. Furthermore, use of intensive lipid-lowering strategies with statins and non-statin drugs leads to decrease of ischaemic major adverse cardiac events, without safety concern, in a large population of patients with atherosclerotic cardiovascular disease (ASCVD). These data should promote the concept ‘the earlier, the lower, the longer, the better’ for the lipid management of patients with ASCVD. While few uncertainties remain in several populations that have been underrepresented in clinical trials (African American and Asian patients, low weight individuals), the most recent data with intensive LDL-C lowering with PCSK9 inhibitors are reassuring that the benefit outweighs any possible risk.

Objective Knee osteoarthritis (OA) is a disease of multiple phenotypes of which a chronic pain phenotype (PP) is known. Previous PP studies have focused on one domain of pain and included heterogenous variables. We sought to identify multidimensional PPs using the IMMPACT recommendations and their relationship to clinical outcomes. Methods Participants >40 years of age with knee OA having a first-time orthopedic consultation at five university affiliated hospitals in Montreal, Quebec, and Hamilton (Canada) were recruited. Latent profile analysis was used to determine PPs (classes) using variables recommended by IMMPACT. This included pain variability, intensity and qualities, somatization, anxiodepressive symptoms, sleep, fatigue, pain catastrophizing, neuropathic pain, and quantitative sensory tests. We used MANOVA and χ2 tests to assess differences in participant characteristics across the classes and linear and Poisson regression to evaluate the association of classes to outcomes of physical performance tests, self-reported function and provincial healthcare data. Results In total, 343 participants were included (mean age 64 years, 64% female). Three classes were identified with increasing pain burden (class3 > class1), characterized by significant differences across most self-report measures and temporal summation, and differed in terms of female sex, younger age, lower optimism and pain self-efficacy. Participants in class2 and class3 had significantly worse self-reported function, stair climb and 40 m walk tests, and higher rates of healthcare usage compared to those in class1. Conclusions Three distinct PPs guided by IMMPACT recommendations were identified, predominated by self-report measures and temporal summation. Using this standardized approach may improve PP study variability and comparison.

ObjectiveTo determine if the changes in the European Society Cardiology/European Atherosclerotic Society (ESC/EAS) guidelines improved the identification for primary prevention therapy in young adults at risk of a premature myocardial infarction.MethodsPatients admitted for a first ST-segment elevation myocardial infarction (STEMI) in the ePARIS registry (n=2757) between 2010 and 2018 were classified by age: 65 years old. Using Systematic Coronary Risk Estimation 2, we evaluated whether patients would have been detected and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines. Eligibility for intensive proprotein convertase subtilisin/kexin type 9 (PCSK9i) in secondary prevention was also assessed.ResultsFollowing 2021 ESC guidelines, 62.5% of individuals aged 65 years old (19% and 72%), p65 years.ConclusionsThe 2021 ESC guidelines allowed a much better detection of young individuals before their first STEMI than prior ESC guidelines. In secondary prevention, most of young individuals did not reach low-density lipoprotein cholesterol levels recommended, but only one quarter would be eligible for PCSK9i.