Journal of Cardiovascular Pharmacology最新文献

Abstract: Uncontrolled hypertension remains a major contributor to cardiovascular morbidity and mortality. Lorundrostat directly reduces aldosterone synthesis and represents a targeted therapeutic strategy. The aim of this study was to evaluate the comparative efficacy and safety of lorundrostat among adults with uncontrolled or treatment-resistant hypertension. We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 guidelines and identified relevant randomized controlled trials from PubMed, ScienceDirect, and CENTRAL databases through August 2025. Data for various outcomes were extracted after computing the risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. We included 3 randomized controlled trials, with 1165 patients receiving lorundrostat and 403 patients receiving placebo. The efficacy outcomes demonstrated a significant reduction in systolic blood pressure (MD: -8.00; 95% CI: -10.81 to -5.19; P < 0.00001) and diastolic blood pressure (DBP) (MD: -3.31; 95% CI: -5.56 to -1.07; P = 0.004) with lorundrostat. Regarding safety outcomes, lorundrostat reported a higher incidence of adverse events (RR: 1.47; 95% CI: 1.29 to 1.67; P < 0.00001), hyperkalemia (RR: 9.17; 95% CI: 2.24 to 37.44; P = 0.002), and symptomatic hypotension (RR: 2.97; 95% CI: 1.12 to 7.90; P = 0.03), whereas the incidence of serious adverse events (RR: 1.29; 95% CI: 0.33 to 5.03; P = 0.71) was comparable between the 2 groups. Lorundrostat effectively reduced blood pressure; however, its use was accompanied by increased adverse events, hyperkalemia, and symptomatic hypotension. Efficacy must therefore be weighed carefully against safety, taking into account the patients' baseline characteristics.

Abstract: Low-dose aspirin has a well-established role in secondary prevention of cardiovascular disease, but use in primary prevention remains uncommon due to limited evidence of benefit and risk of adverse effects such as bleeding. While benefit of aspirin in primary prevention may not outweigh risk in the general population, it may still be appropriate for particular groups in which benefit would be greater. Novel biomarkers for cardiovascular risk can help identify these groups. These include imaging markers such as coronary artery calcium scoring and carotid plaque assessment, and laboratory markers such as lipoprotein(a) and high-sensitivity C-reactive protein. Use of these biomarkers for more effective risk stratification can delineate groups of patients with greater potential benefit from aspirin and help guide risk-benefit conversations regarding primary prevention.

Abstract: Atherosclerotic cardiovascular disease remains a leading cause of death globally. Cholesteryl ester transfer protein (CETP) inhibitors have been proposed as a novel strategy for cardiovascular risk reduction, yet evidence remains inconsistent. PubMed, EMBASE, and Scopus were searched for randomized controlled trials comparing CETP inhibitors with placebo in patients with atherosclerotic cardiovascular disease. Random-effects models were used to pool risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I 2 statistics. Statistical analysis was performed using R software version 4.3.3. We included 5 RCTs involving 62,565 participants, of whom 31,698 (50.7%) received CETP inhibitors. Compared with placebo, CETP inhibitors showed no significant reduction in death from coronary heart disease (RR: 0.91; 95% CI, 0.82 to 1.01), unplanned coronary revascularization (RR: 0.91; 95% CI, 0.79-1.05), nonfatal myocardial infarction (RR: 0.94; 95% CI, 0.87-1.02), and stroke (RR: 1.02; 95% CI, 0.93-1.12). In addition, no excess risk of adverse events was observed (RR: 1.00; 95% CI, 0.99-1.02). Conversely, HDL-C (MD: +130.82%; 95% CI, 121.49-140.15), LDL-C (MD: -32.68%; 95% CI, -40.73 to -24.63), ApoA1 (MD: +45.04%; 95% CI, 40.51-49.57), and Apo B (MD: -17.26%; 95% CI, -20.51 to -14.00) showed significant improvement. CETP inhibitors produce substantial lipid modifications but do not reduce major adverse cardiovascular events, underscoring the limitations of surrogate lipid markers and the need for outcome-based validation of lipid-modifying therapies.

Abstract: Mineralocorticoid receptor activation contributes to cardiovascular and kidney injury through inflammation, fibrosis, oxidative stress, endothelial dysfunction, and adverse tissue remodeling. Eplerenone, a selective steroidal mineralocorticoid receptor antagonist (MRA) developed to minimize the endocrine adverse effects associated with spironolactone, has demonstrated substantial clinical benefits in patients with post-myocardial infarction left ventricular dysfunction and heart failure with reduced ejection fraction, where its role is well established. This review examines the evolving evidence supporting eplerenone across cardiovascular and renal diseases, including hypertension, left ventricular hypertrophy, albuminuria, and broader cardiorenal risk reduction. Although accumulating data suggest potential benefits in these settings, the strength of evidence varies considerably across indications. Spironolactone remains the MRA with the strongest evidence for resistant hypertension, whereas finerenone has generated the most robust dedicated kidney outcomes data in patients with diabetic chronic kidney disease. We conclude that eplerenone should be viewed neither as simply an alternative for spironolactone intolerance nor as a universal substitute for newer MRAs. Rather, it remains an evidence-based, well-tolerated therapy with a firmly established role in post-myocardial infarction left ventricular dysfunction and heart failure with reduced ejection fraction, together with a potentially valuable role in selected hypertensive and cardiorenal populations where selective mineralocorticoid receptor blockade and long-term tolerability are important clinical considerations.

Background: Corticosteroids are widely used in pericarditis despite guideline recommendations reserving them for select indications. Observational studies have reported inconsistent associations between corticosteroid use and pericarditis recurrence, and optimal dosing and tapering strategies remain unclear. We conducted a systematic review of oral corticosteroids for acute or recurrent pericarditis to characterize patterns of treatment and evaluate the association between corticosteroids and pericarditis recurrence across different disease contexts.

Methods: MEDLINE, Embase, CENTRAL, and Scopus were searched from inception to November 26, 2025. Studies enrolling adults with acute or recurrent pericarditis treated with oral corticosteroids were included. Randomized trials, cohort studies, and case-control studies reporting clinical outcomes were eligible. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data were synthesized descriptively due to anticipated clinical and methodological heterogeneity.

Results: Ten studies (2 prospective and 8 retrospective) including 2632 patients (800 corticosteroid treated) met inclusion criteria. Prednisone was most frequently studied, with heterogeneous dosing (0.25-1.0 mg/kg/d) and nonstandardized tapering strategies. Follow-up ranged from 1 to 6.7 years, and overall risk of bias was moderate with limited adjustment for confounding. Findings on recurrence were inconsistent in acute idiopathic and postprocedure pericarditis, while most studies in recurrent pericarditis reported higher recurrence with corticosteroid exposure.

Conclusions: Evidence evaluating oral corticosteroids in pericarditis is limited by heterogeneity, confounding, and inconsistent reporting of treatment strategies. Observational data show variable associations with recurrence across clinical contexts. High-quality randomized trials stratified by pericarditis etiology and acuity are needed to define the optimal use of corticosteroids in pericarditis.

Abstract: Machine learning (ML) models integrating genetic and clinical data show promise for personalizing antiplatelet therapy after myocardial infarction (MI). This study aimed to develop an ML model using clinical features and CYP2C19 genotype to predict long-term major adverse cardiac events (MACEs) and guide P2Y12 inhibitor selection. In a prospective observational study of 218 patients with MI undergoing percutaneous coronary intervention, with up to 9-year follow-up for MACEs, we trained and evaluated multiple models incorporating clinical, genetic, and angiographic variables. Uplift modeling principles were applied to assess treatment heterogeneity, and feature importance was analyzed using Shapley Additive Explanations (SHAP). The optimal model (CatBoost with SHAP-based feature selection) achieved an area under the receiver operating characteristic curve of 0.721. Discrimination remained stable under bootstrap resampling and across both infarction presentations. Key prognostic predictors included age, comorbidity index, number of significant coronary lesions, P2Y12 inhibitor type, stent type, and CYP2C19 loss-of-function/gain-of-function variants. Notably, CYP2C19 variants were significant MACE predictors, while drug-eluting stents and ticagrelor were associated with lower predicted long-term risk. These findings suggest that an ML framework incorporating CYP2C19 genotype can stratify long-term MACE risk. This data-driven approach points to the prognostic utility of genetic testing and supports the potential role of ticagrelor, particularly in genetically defined high-risk patients with MI, for optimizing secondary prevention.

Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a key component of lipid-lowering therapies for atherosclerotic cardiovascular disease risk management in high-risk primary and secondary prevention populations. PCSK9 monoclonal antibodies such as evolocumab and alirocumab were the first agents approved and are the preferred agents, given the phase 3 trial data supporting improved cardiovascular outcomes. Subgroup analyses of these trials have highlighted high-risk populations that may especially benefit from PCSK9 inhibitor therapy, although demographic disparities persist regarding their implementation. Additional injectable agents with less-frequent dosing schedules have been developed, such as the small-interfering RNA inclisiran, although they lack data regarding cardiovascular outcomes. Oral agents are also in development, with promising data recently presented regarding enlicitide. In addition, recent trials provide evidence supporting expanded indications for high-risk primary prevention. This review summarizes currently available and investigational PCSK9-targed therapies and examines evidence guiding their clinical implementation.

Abstract: Type 2 myocardial infarction (T2MI) results from myocardial oxygen supply-demand imbalance in the absence of acute atherothrombotic plaque rupture and is associated with substantial short-term and long-term mortality. Although increasingly recognized with the widespread use of high-sensitivity cardiac troponin assays, optimal pharmacologic management of T2MI remains poorly defined. We performed a narrative review evaluating pharmacologic treatment patterns and outcomes in adults with adjudicated or clinically coded T2MI. Evidence consistently demonstrates a high prevalence of underlying coronary artery disease in T2MI, with up to two-thirds of patients exhibiting significant coronary artery stenosis. Despite this overlap with ischemic heart disease, prescription rates of antiplatelet agents, statins, β-blockers, and renin-angiotensin-aldosterone system inhibitors are substantially lower in T2MI compared with type 1 myocardial infarction. Observational data suggest that statins, β-blockers, renin-angiotensin-aldosterone system inhibitors, and combination secondary prevention strategies may be associated with improved survival, whereas evidence supporting routine antiplatelet or anticoagulant therapy remains limited and inconsistent. Overall, T2MI represents a high-risk and underrecognized clinical entity for which pharmacologic management is largely extrapolated from type 1 myocardial infarction and coronary artery disease. Prospective, T2MI-focused studies are urgently needed to define optimal secondary prevention strategies and improve clinical outcomes.