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The prevention of stroke and restenosis of coronary arteries in patients with atrial fibrillation who have an acute coronary syndrome or undergo percutaneous coronary intervention relies on antithrombotic therapy. In a two-by-two factorial, randomized trial, apixaban plus clopidogrel was more effective than a vitamin K antagonist, with or without aspirin.

In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either sacubitril–valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure.

Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.

Jane Hirst and colleagues argue that novel modelling approaches using routinely collected data can be only as representative and complete as the original data, and that bridging the sex and gender gap through contemporary, innovative clinical trial designs could be a crucial way forward

We aimed to quantify the blood pressure-lowering efficacy of antihypertensive drugs and their combinations from the five major drug classes. We conducted a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials involving adult participants randomly assigned to receive angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, or diuretics. Eligibility criteria included follow-up duration between 4 weeks and 26 weeks, antihypertensive drug treatment fixed in all participants for at least 4 weeks before follow-up blood pressure assessment; and availability of clinic blood pressure for the calculation of mean difference in systolic blood pressure between treatment groups. Crossover trials with less than 2 weeks’ washout between the crossover periods were excluded. Eligible studies published between database inception and Dec 31, 2022 were identified from searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Epistemonikos; searches were updated to include studies published between Jan 1, 2023, and Feb 28, 2025. The primary outcome was placebo-corrected reduction in systolic blood pressure. Blood pressure-lowering efficacy was estimated using fixed-effects meta-analyses standardised to mean baseline blood pressure across included trials. Drug regimens were categorised into low, moderate, and high intensity, corresponding to systolic blood pressure-lowering efficacy of <10 mm Hg, 10–19 mm Hg, and ≥20 mm Hg, respectively, from a baseline of 154 mm Hg. A model was developed to calculate efficacy for any combination of antihypertensives and validated on external trials of dual and triple combination antihypertensives. The study protocol was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202410036). We analysed 484 trials including 104 176 participants (mean age 54 years [SD 8], 57 422 [55%] men, 46 754 [45%] women, and mean baseline systolic blood pressure 154/100 mm Hg). Mean follow-up duration was 8·6 weeks (SD 5·2). On average, monotherapy at standard dose reduced systolic blood pressure by 8·7 mm Hg (95% CI 8·2–9·2), and each doubling in dose conferred an additional 1·5 mm Hg (1·2–1·7) reduction. Dual combinations at one standard dose conferred a 14·9 mm Hg (95% CI 13·1–16·8) reduction in systolic blood pressure, with each doubling of doses of both drugs conferring an additional reduction of 2·5 mm Hg (1·4–3·7). Each 10 mm Hg decrease in baseline systolic blood pressure reduced pressure-lowering efficacy by 1·3 mm Hg (1·0–1·5) for monotherapies, although differences between drug classes were observed. Among 57 monotherapies at standard dose, 45 (79%) were classified as low intensity. Of 189 different drug–dose dual combinations, 110 (58%) were classified as moderate intensity, and 21 (11%) as high intensity. There were considerable differences in dose–response and baseline blood pressure–response relationships between and within drug classes. The efficacy model showed a high correlation between predicted and observed systolic blood pressures when validated on external trials (r=0·76, p<0·0001). These analyses provide robust estimates of the expected blood pressure-lowering effect for any combination of antihypertensive drugs, allowing their efficacy to be classified into low, moderate, and high intensity. National Health and Medical Research Council, Australia.

BackgroundMost of the evidence on bariatric surgery on obstructive sleep apnea (OSA) is based on observational studies and/or short-term follow-up in patients with obesity grade 3.Subjects/MethodsThis randomized study compared the effects of roux-en-Y gastric bypass (RYGB) or usual care (UC) on OSA severity in patients with obesity grade 1–2. Mild, moderate, and severe OSA was defined by the apnea-hypopnoea index (AHI): 5–14.9; 15–29.9, and ≥30 events/h, respectively. OSA remission was defined by converting any form of OSA into normal AHI (<5 events/h).ResultsAfter 3-year of follow-up, the body-mass index increased in the UC while decreased in the RYGB group: +1.7 (−1.9; 2.7) versus −10.6 (−12.7; −9.2) kg/m2, respectively. The AHI increased by 5 (−4.2; 12.7) in the UC group while reduced in the RYGB group to −13.2 (−22.7; −7) events/h. UC significantly increase the frequency of moderate OSA (from 15.4 to 46.2%). In contrast, RYGB had a huge impact on reaching no OSA status (from 4.2 to 70.8%) in parallel to a decrease of moderate (from 41.7 to 8.3%) and severe OSA (from 20.8 to 0%).ConclusionsRYGB is an attractive strategy for mid-term OSA remission or decrease moderate-to-severe forms of OSA in patients with obesity grade 1–2.

High-quality, adequately powered, simple randomised clinical trials have been crucial in advancing knowledge of potential treatments for COVID-19.1 Principles underpinning such trials include the use of the uncertainty principle to determine eligibility, which allows for rapid enrolment of participants and streamlined data collection, making these studies easy to implement in routine practice.2 Platform and adaptive trial designs further improve the large, simple trial concept, allowing investigation of multiple experimental therapies throughout the trial with sufficient statistical power for clinically relevant outcomes.3 RECOVERY represents a large, simple, randomised platform trial. The results of this investigation into azithromycin as part of the RECOVERY trial confirm and extend those of the COALITION II trial,8 which showed that the addition of azithromycin to standard of care treatment did not improve the clinical outcomes of patients admitted to hospital with severe COVID-19. The experience and the knowledge gained from successfully launching these studies in a matter of weeks has important implications for research not only in COVID-19 but also for future pandemics and for common diseases.12 Finally, innovations such as big data technologies and linkage with electronic health records, mobile applications, and wearable devices can further transform pragmatic randomised clinical trials, making them larger, more efficient, and easier to implement.

•Few quality improvement interventions have successfully improved LDL-C control.•Active strategies tackling healthcare providers and patients’ barriers in an integrated manner may be beneficial.•A digitally enabled quality improvement intervention assessed in a cluster randomized trial would be highly useful in promoting optimal LDL-C control in ASCVD patients. Translating evidence into clinical practice in the management of established atherosclerotic cardiovascular disease patients is challenging. Few quality improvement interventions have successfully improved patient care. The main objectives are to evaluate the impact of a digitally enabled multifaceted quality improvement (QI) intervention on the control of LDL-cholesterol (LDL-C) in atherosclerotic cardiovascular disease (ASCVD). We designed a pragmatic 2-arm cluster randomized trial involving 28 clusters (outpatient clinics from public or private hospitals or private practices). Clusters are randomized to receive a digitally enabled multifaceted QI intervention or to routine practice (control). The QI intervention includes reminders, electronic clinical decision support algorithms, audit and feedback reports, and distribution of educational materials to health care providers, as well as electronic educational materials and app-based tools for drug adherence control, lipid profile control, and communication to participants. The primary endpoint is the LDL-C at 06 months after the intervention period. All analyses are performed following the intention-to-treat principle and take the cluster design into consideration by using individual-level regression modeling (generalized estimating equations-GEE). If proven effective, this low-cost, digitally enabled multifaceted QI intervention would be highly useful in promoting optimal LDL-C control in ASCVD patients. ClinicalTrials.gov NCT05622929.

Early termination of clinical trials due to low recruitment represents an understudied challenge for clinical research. We aimed to describe characteristics of cardiovascular trials terminated because of low recruitment and identify the major predictors of such early termination. We reviewed all cardiovascular clinical trials (7,042 studies) registered in ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed information about trials that were completed and those that were terminated early. Logistic regression models were developed to identify independent predictors of early termination due to low recruitment. Our search strategy identified 6,279 cardiovascular clinical trials, of which 684 (10.9%) were terminated prematurely. Of these halted trials, the main reason for termination was lower than expected recruitment (278 trials; 53.6%). When comparing trials that terminated early because of low recruitment with those that were completed, we found that studies funded by the National Institutes of Health or other US federal agencies (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65), and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a lower risk of early termination. University/hospital-funded (OR 1.52, 95% CI 1.10-2.10) and mixed-source–funded studies (OR 2.14, 95% CI 1.52-3.01) were associated with a higher likelihood of early termination due to lower than expected recruitment rates. Low recruitment represents the main cause of early termination of cardiovascular clinical trials. Funding source, type of intervention, and study design are factors associated with early termination due to low recruitment and might be good targets for improving enrollment into cardiovascular clinical trials.