Background: Aldosterone synthase inhibitors (ASIs) have emerged as a mechanistically targeted strategy for resistant and uncontrolled hypertension; however, no head-to-head trials exist, and comparative efficacy and safety remain uncertain. We compared their efficacy and safety using network and pairwise meta-analysis of randomized trials. Methods: This systematic review and meta-analysis adhered to the PRISMA guidelines. PubMed/MEDLINE, Scopus, Embase, ClinicalTrials.gov, and Cochrane Library were searched from inception to January 14, 2026, for randomized trials evaluating ASIs versus placebo or standard care. A frequentist random-effects network meta-analysis assessed systolic (SBP) and diastolic blood pressure (DBP). Dichotomous safety outcomes were pooled using Hartung–Knapp random-effects models. Network consistency was evaluated using design-by-treatment interaction modeling. Prespecified subgroup analyses stratified outcomes by hypertension phenotype (resistant vs uncontrolled). Results: Across 7 RCTs (n = 2,828), all ASIs significantly reduced SBP versus placebo: baxdrostat −8.63 mmHg (95% CI −10.84 to −6.42), lorundrostat −7.47 mmHg (95% CI −9.54 to −5.40), and LCI699/osilodrostat −5.63 mmHg (95% CI −9.15 to −2.12), with no significant indirect differences between agents. In resistant hypertension, lorundrostat (−9.00 mmHg; 95% CI −13.19 to −4.81) and baxdrostat (−8.77 mmHg; 95% CI −10.50 to −7.05) demonstrated pronounced reductions. In uncontrolled hypertension, LCI699/osilodrostat showed the largest point estimate (−10.55 mmHg; 95% CI −16.49 to −4.61), though this derives from a single early-phase trial and requires cautious interpretation. DBP reductions were significant for baxdrostat (−3.23 mmHg; 95% CI −4.73 to −1.73) and lorundrostat (−3.60 mmHg; 95% CI −5.43 to −1.77). Hypotension (RR 2.67), hyperkalemia (RR 7.94), and hyponatremia (RR 2.07) were significantly increased; serious adverse events, discontinuation, and network inconsistency were not detected. Conclusions: ASIs provide clinically meaningful BP reduction across both hypertension phenotypes; however, short-term use is associated with hypotension and electrolyte disturbances, necessitating careful monitoring. Phenotype-specific efficacy and long-term safety require validation in outcome-driven trials. Systematic Review Registration: PROSPERO CRD420251266257

Background: Early aspirin discontinuation followed by P2Y12 inhibitor monotherapy is increasingly used after percutaneous coronary intervention (PCI), yet whether the timing of discontinuation within the early post-procedural period modifies clinical outcomes remains uncertain. Methods: We searched PubMed/MEDLINE, Scopus, Embase, CENTRAL, and ClinicalTrials.gov through March 5, 2026, for randomized controlled trials evaluating early aspirin discontinuation with P2Y12 inhibitor monotherapy versus continued dual antiplatelet therapy (DAPT) in adults undergoing PCI. Outcomes included major bleeding, stent thrombosis, myocardial infarction (MI), major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and net adverse clinical events (NACE). Results: Ten RCTs comprising 52,793 participants were included. Early aspirin discontinuation significantly reduced major bleeding (HR 0.59; 95% CI, 0.43–0.79; p = 0.0004), any bleeding (HR 0.52; 95% CI, 0.41–0.66; p < 0.0001), and NACE (HR 0.86; 95% CI, 0.76–0.97; p = 0.017), without significant increases in MI, MACE, or mortality. Stent thrombosis was significantly increased (HR 1.35; 95% CI, 1.03–1.78; p = 0.033; I ² = 0%), with a directional gradient from HR 1.62 at 0 days to HR 0.81 at 90 days. Meta-regression found no significant association between discontinuation timing and any outcome (all p > 0.05). Hartung-Knapp sensitivity analysis did not materially alter pooled estimates. Conclusions: Early aspirin discontinuation after PCI reduces bleeding and improves net clinical outcomes without significant increases in MI, MACE, or mortality, but modestly increases stent thrombosis. Discontinuation timing within 0 to 90 days was not statistically associated with treatment effects; however, this finding is hypothesis-generating given limited power across only three discontinuation nodes.

Cardiometabolic diseases (CMDs) disproportionately affect vulnerable populations worldwide. Community health worker (CHW)–led interventions may reduce risk and improve preventive care, but their effectiveness remains unclear. This systematic review and meta-analysis evaluated their effectiveness on cardiometabolic outcomes in vulnerable groups. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, ClinicalTrials.gov, and Cochrane Library was performed from January 1, 2000 to December 20, 2025, for randomized trials of CHW-led interventions on cardiometabolic outcomes. Primary outcomes were systolic and diastolic blood pressure; secondary outcomes were body mass index (BMI), glycosylated hemoglobin (HbA1c), and low-density lipoprotein cholesterol (LDL-C). Outcomes were pooled as mean differences using the generic inverse variance method; heterogeneity was assessed using I ² . Thirty randomized trials (15,295 participants) were included. CHW-led interventions significantly improved systolic blood pressure (WMD = −3.72 mmHg; 95% CI: −5.94 to −1.51; I ² = 99.1%) and diastolic blood pressure (WMD = −2.22 mmHg; 95% CI: −3.50 to −0.95; I ² = 98.6%); 95% prediction intervals crossed the null for all five outcomes (e.g., SBP: −15.12 to 7.67 mmHg), indicating uncertainty at a new site. BMI and HbA1c improved modestly but were attenuated to non-significance by trim-and-fill analysis, suggesting publication bias; LDL-cholesterol effects were not significant. SBP reductions were significant in low- and middle-income countries (LMICs) (WMD = −5.09 mmHg; 95% CI: −7.57 to −2.60) but not high-income countries (HICs), with the largest effects in Africa. GRADE certainty was low for blood pressure, moderate for BMI, very low for HbA1c, and low for LDL-cholesterol. CHW-led interventions modestly improve cardiometabolic outcomes in vulnerable populations, with low-to-very-low certainty evidence for blood pressure and glycemic control and moderate certainty for BMI, supporting a potential role in cardiovascular risk-reduction strategies, particularly in LMICs. However, wide prediction intervals and non-significant meta-regression for intervention design features (contact frequency, duration, delivery format) warrant cautious, hypothesis-generating interpretation pending higher-quality trials. Systematic review Registration: Registration Number: PROSPERO 2025 CRD420251248842

Background: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), termed COPD-associated pulmonary hypertension (COPD-PH), and is associated with worse clinical outcomes. The efficacy and safety of pulmonary vasodilators in COPD-PH remain uncertain. Methods: We performed a systematic review and meta-analysis of randomized studies evaluating pulmonary vasodilators in adults with COPD-PH. Fifteen studies were identified, with 11 contributing to quantitative analyses. Outcomes included six-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), partial pressure of arterial oxygen (PaO₂), and systolic pulmonary arterial pressure (sPAP). Results: Pulmonary vasodilators significantly reduced mPAP (MD −3.88 mmHg, 95% CI −7.23 to −0.53) and PVR (SMD −0.90, 95% CI −1.70 to −0.10). However, no significant improvements were observed in 6MWD or PaO₂. An exploratory composite hemodynamic score supported an overall hemodynamic benefit. Subgroup analyses suggested a more favorable profile for nitric oxide donors, whereas endothelin receptor antagonists were associated with worsened oxygenation. Conclusions: Pulmonary vasodilators improve pulmonary hemodynamics in COPD-PH but do not consistently improve exercise capacity or oxygenation. Current evidence does not support routine use outside specialized centers or clinical trials, and treatment effects appear to vary by drug class.