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Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels. In this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary end point was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group. A total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of -20.3 mm Hg, -17.5 mm Hg, -12.1 mm Hg, and -9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was -11.0 mm Hg (95% confidence interval [CI], -16.4 to -5.5; P<0.001), and the difference in this change between the 1-mg group and the placebo group was -8.1 mm Hg (95% CI, -13.5 to -2.8; P = 0.003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug. Patients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure. (Funded by CinCor Pharma; BrigHTN ClinicalTrials.gov number, NCT04519658.).

We extend previous studies on the impact of masks on COVID-19 outcomes by investigating an unprecedented breadth and depth of health outcomes, geographical resolutions, types of mask mandates, early versus later waves and controlling for other government interventions, mobility testing rate and weather. We show that mask mandates are associated with a statistically significant decrease in new cases (-3.55 per 100K), deaths (-0.13 per 100K), and the proportion of hospital admissions (-2.38 percentage points) up to 40 days after the introduction of mask mandates both at the state and county level. These effects are large, corresponding to 14% of the highest recorded number of cases, 13% of deaths, and 7% of admission proportion. We also find that mask mandates are linked to a 23.4 percentage point increase in mask adherence in four diverse states. Given the recent lifting of mandates, we estimate that the ending of mask mandates in these states is associated with a decrease of -3.19 percentage points in mask adherence and 12 per 100K (13% of the highest recorded number) of daily new cases with no significant effect on hospitalizations and deaths. Lastly, using a large novel survey dataset of 847 thousand responses in 69 countries, we introduce the novel results that community mask adherence and community attitudes towards masks are associated with a reduction in COVID-19 cases and deaths. Our results have policy implications for reinforcing the need to maintain and encourage mask-wearing by the public, especially in light of some states starting to remove their mask mandates.

This study determined the effect of systolic and diastolic hypertension on a composite of myocardial infarction, ischemic stroke, or hemorrhagic stroke in 1.3 million adult outpatients. Systolic blood-pressure elevation affected outcomes more, but systolic and diastolic hypertension independently influenced cardiovascular risk.

Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. None.

The magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined. We did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018. Data search and extraction were completed with a standardised data form and any discrepancies were resolved by consensus. Efficacy outcomes included major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease. Hazard ratios (HRs) with 95% CIs were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function. We included data from three identified trials and 34 322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (HR 0·89 [95% CI 0·83–0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80–0·93]) and not in those without (1·00 [0·87–1·16], p for interaction=0·0501). SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71–0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48–0·64], p<0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease. The magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline. SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atherosclerotic cardiovascular disease. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure. None.

Five-year data showed that among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing or resolving hyperglycemia, even among those with a BMI of less than 35. Observational studies 1 – 6 and randomized, controlled trials, which have generally been short-term studies, 7 – 19 have shown that bariatric surgery, when used specifically to treat diabetes, significantly improves glycemic control and reduces cardiovascular risk factors. In the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, we reported that, at 1 year and 3 years after randomization, both gastric bypass and sleeve gastrectomy were superior to intensive medical therapy alone in achieving excellent glycemic control (i.e., glycated hemoglobin ≤6.0%), reducing cardiovascular risk, improving quality of life, and decreasing medication use. 8 – 10 The current article provides results of the final, 5-year . . .

Aspirin monotherapy is recommended indefinitely for patients with established coronary artery disease (CAD). The aim of this individual patient level meta-analysis was to provide a comprehensive evaluation of the comparative efficacy and safety of clopidogrel versus aspirin monotherapy in patients with established CAD, most of whom had undergone percutaneous coronary intervention or had acute coronary syndrome. We conducted a systematic search in PubMed, Scopus, Web of Science, and Embase to identify randomised trials published from database inception to April 12, 2025, comparing clopidogrel monotherapy with aspirin monotherapy in patients with established CAD who had discontinued or never started dual antiplatelet therapy. Randomised trials featuring an initial phase of dual antiplatelet therapy were eligible for inclusion in this individual patient data meta-analysis. In the main analysis, we used semi-parametric shared log-normal frailty models (one-stage analysis), including a random intercept to account for differences in the baseline hazard across trials, and a random slope to account for between-trial differences in treatment effects. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular or cerebrovascular events [MACCE]); the primary safety endpoint was major bleeding. This study is registered with PROSPERO (CRD42025645594). Seven randomised trials including 28 982 patients (14 507 assigned to clopidogrel; 14 475 assigned to aspirin) with a median follow-up of 2·3 years (IQR 1·1–4·0) were eligible and included. At 5·5 years, MACCE was less common in patients assigned to clopidogrel than in patients assigned to aspirin (929 events [2·61 per 100 patient-years] vs 1062 events [2·99 per 100 patient-years]; hazard ratio 0·86 [95% CI 0·77–0·96]; p=0·0082). Mortality and major bleeding (256 events [0·71 per 100 patient-years] with clopidogrel vs 279 events [0·77 per 100 patient-years] with aspirin; 0·94 [0·74–1·21]; p=0·64) did not differ. These findings add to the evidence that clopidogrel monotherapy is superior to aspirin monotherapy for MACCE prevention with no increase in the risk of bleeding, and support the preferential use of clopidogrel over aspirin for secondary prevention in patients with established CAD. Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Switzerland.

The optimum blood pressure target in hypertension remains debated, especially in coronary artery disease, given concerns for reduced myocardial perfusion if diastolic blood pressure is too low. We aimed to study the association between achieved blood pressure and cardiovascular outcomes in patients with coronary artery disease and hypertension. We analysed data from 22 672 patients with stable coronary artery disease enrolled (from Nov 26, 2009, to June 30, 2010) in the CLARIFY registry (including patients from 45 countries) and treated for hypertension. Systolic and diastolic blood pressures before each event were averaged and categorised into 10 mm Hg increments. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HRs) were estimated with multivariable adjusted Cox proportional hazards models, using the 120–129 mm Hg systolic blood pressure and 70–79 mm Hg diastolic blood pressure subgroups as reference. After a median follow-up of 5·0 years, increased systolic blood pressure of 140 mm Hg or more and diastolic blood pressure of 80 mm Hg or more were each associated with increased risk of cardiovascular events. Systolic blood pressure of less than 120 mm Hg was also associated with increased risk for the primary outcome (adjusted HR 1·56, 95% CI 1·36–1·81). Likewise, diastolic blood pressure of less than 70 mm Hg was associated with an increase in the primary outcome (adjusted HR 1·41 [1·24–1·61] for diastolic blood pressure of 60–69 mm Hg and 2·01 [1·50–2·70] for diastolic blood pressure of less than 60 mm Hg). In patients with hypertension and coronary artery disease from routine clinical practice, systolic blood pressure of less than 120 mm Hg and diastolic blood pressure of less than 70 mm Hg were each associated with adverse cardiovascular outcomes, including mortality, supporting the existence of a J-curve phenomenon. This finding suggests that caution should be taken in the use of blood pressure-lowering treatment in patients with coronary artery disease. Servier.

In this large trial, denervation of the kidneys with use of a radiofrequency ablation catheter in the renal arteries had no significant effect on blood pressure in patients with resistant hypertension. This contradicts results of smaller trials that did not include a sham control. Because of the aging of the population and rising rates of obesity, hypertension is increasing in prevalence worldwide. 1 Approximately 10% of patients with diagnosed hypertension have resistant hypertension, defined as a systolic blood pressure of 140 mm Hg or higher despite adherence to at least three maximally tolerated doses of antihypertensive medications from complementary classes, including a diuretic at an appropriate dose. 1 – 4 Patients with resistant hypertension who are receiving appropriate medical therapy have high rates of cardiovascular complications, with few treatment options. The sympathetic nervous system — in particular, sympathetic cross-talk between the kidneys and the brain — appears . . .