American Journal of Cardiovascular Drugs最新文献

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated efficacy and safety in patients with type 2 diabetes mellitus, chronic kidney disease, and heart failure. However, their effects in heart transplant recipients, a population with high cardiovascular risk, remain poorly understood.

Methods: Clinical trials and observational studies were included. A systematic search was conducted in PubMed, Scopus, EMBASE, and Web of Science. Mean differences (MD) were calculated for continuous outcomes and risk ratios (RR) for binary outcomes, both with 95% confidence intervals (CI). Analyses were performed using RevMan version 5.4.1.

Results: Five retrospective cohort studies including 1512 heart transplant recipients (312 SGLT2i users and 1200 controls) were analyzed. SGLT2i use was not associated with significant changes in renal function (MD in eGFR: 3.96 mL/min/1.73 m²; 95% CI: - 2.33 to 10.26; p = 0.22) or glycemic control (MD in HbA1c: - 0.20%; 95% CI: - 0.73 to 0.34; p = 0.47). Mortality was comparable between groups (RR: 0.64; 95% CI: 0.29-1.40; p = 0.26), with no significant increase in urinary tract infections (RR: 1.40; 95% CI: 0.25-7.72; p = 0.70). However, SGLT2i use was associated with significant reductions in body mass index (MD: - 0.90 kg/m²; 95% CI: - 1.67 to - 0.14; p = 0.02) and systolic blood pressure (MD: - 4.69 mmHg; 95% CI: - 7.27 to - 2.12; p < 0.001).

Conclusions: In heart transplant recipients, the use of SGLT2 inhibitors was not associated with significant improvements in renal function or glycemic control and did not increase mortality or the incidence of urinary tract infections. However, SGLT2 inhibitor therapy was associated with significant reductions in body mass index and systolic blood pressure, suggesting a potential cardiometabolic benefit in this high-risk population. Given that hypertension and obesity are well-established cardiovascular risk factors and that hypertension, in particular, is a common complication among heart transplant recipients, these blood pressure and weight-lowering effects may be clinically meaningful.

Systematic review registration: PROSPERO CRD420251057335.

Background: The optimal anticoagulation strategy for patients with atrial fibrillation (AF) and obstructive hypertrophic cardiomyopathy (oHCM) remains unclear. This study compared the outcomes of direct oral anticoagulants (DOACs) versus warfarin in this patient population.

Methods: Data from the TriNetX Research Network were used to identify patients with AF and oHCM treated with either DOACs or warfarin. Patients with a prior history of stroke were excluded. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was ischemic stroke. Secondary outcomes included: all-cause death, all-cause hospitalization, acute myocardial infarction, gastrointestinal bleed, hematuria, and brain hemorrhage. Hazard ratios (HRs) were estimated by Cox proportional hazard models.

Results: A total of 7090 patients in the DOAC group and 3350 in the warfarin group were included prior to PSM. Following PSM, each cohort included 3307 patients. The incidence of ischemic stroke was lower in the DOAC group (3.5%) compared with the warfarin group (4.8%), with a hazard ratio (HR) of 0.74 (95% confidence interval [CI]: 0.58-0.95). All-cause mortality was similar between groups, with 555 (16.8%) deaths in the DOAC group and 575 (17.4%) in the warfarin group (HR: 0.996, 95% CI: 0.89-1.12). All-cause hospitalization rates were lower in the DOAC group (64.5%) compared with the warfarin group (68.7%) (HR: 0.90, 95% CI: 0.85-0.95). No significant differences were observed in the rates of acute myocardial infarction (12.1% versus 12.2%; HR: 1.01, 95% CI: 0.88-1.16), gastrointestinal bleeding (6.9% versus 7.9%; HR: 0.89, 95% CI: 0.74-1.06), hematuria (8.0% versus 8.5%; HR: 0.96, 95% CI: 0.82-1.14), or intracranial hemorrhage (1.5% versus 2.0%; HR: 0.75, 95% CI: 0.52-1.09) between groups.

Conclusions: DOACs demonstrated a lower risk of ischemic stroke and all-cause hospitalization rates compared with warfarin in patients with AF and oHCM, supporting the use of DOACs in this patient population.

Background: The long-term benefit of beta-blockers (β-blockers) after myocardial infarction (MI) in patients with preserved left-ventricular ejection fraction (LVEF ≥ 40%) remains uncertain in the modern reperfusion era. Earlier trials showed mortality benefits, but contemporary therapies may have altered their effect.

Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) comparing β-blockers versus no β-blockers in adults with MI and LVEF ≥ 40%. PubMed, Scopus, Web of Science, and Cochrane CENTRAL were searched through October 2025. Primary outcomes were all-cause mortality, recurrent MI, and heart failure (HF). Individual patient data (IPD) were reconstructed from Kaplan-Meier curves for time-to-event analysis, and pooled risk ratios (RRs) and hazard ratios (HRs) were estimated using random-effects models. Trial sequential analysis (TSA), meta-regression, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) certainty assessments were performed.

Results: Five RCTs (n = 23,524 patients) met inclusion criteria. β-Blockers did not significantly reduce recurrent acute myocardial infarction (AMI) (HR: 0.89 with 95% confidence interval [CI 0.78, 1.02], P = 0.1), HF (HR: 0.92 with 95% CI [0.71, 1.20], P = 0.54), and all-cause mortality (HR: 0.97 with 95% CI [0.85, 1.10], P = 0.63). Secondary endpoints-including major adverse cardiovascular events (MACE), cardiovascular death, stroke, and revascularization-were neutral (P > 0.05). TSA boundaries were not crossed, and meta-regression identified no significant effect modifiers. Evidence certainty was rated low to moderate.

Conclusions: Among patients with MI and preserved LVEF, β-blockers did not reduce mortality or ischemic or HF events. Routine long-term use offers no prognostic advantage and should be reserved for specific indications such as reduced LVEF, angina, arrhythmia, or hypertension.

Registration: International Prospective Register of Systematic Reviews (PROSPERO) identifier no. CRD420251175415.

Iron deficiency has been reported in up to 50% of patients with heart failure (HF), irrespective of the presence of anemia. Although no formally validated definition for iron deficiency in patients with HF exists, both the American and European Heart Failure Guidelines define iron deficiency as a serum ferritin of < 100 ng/ml, or a ferritin of 100-299 ng/ml, provided that the transferrin saturation (TSAT) is less than 20%. The presence of iron deficiency has been associated with poor patient-oriented outcomes, prompting the assessment of intravenous (IV) iron as a treatment for iron deficiency. This review summarizes the totality of the evidence on the diagnosis, evaluation and treatment of patients with iron deficiency. In addition, we highlight our approach to patients with HF with reduced ejection fraction and highlight areas for both clinical improvement and research.

Introduction: Heart failure (HF), a leading cause of morbidity and mortality worldwide, continues to pose a therapeutic challenge. Nitroxyl (HNO) donors, such as Cimlanod (BMS-986231 or CXL-1427), are emerging as promising agents owing to their unique vasodilatory, inotropic, and lusitropic properties.

Purpose: This meta-analysis assesses the safety, tolerability, and hemodynamic effects of Cimlanod, in patients with heart failure with reduced ejection fraction (HFrEF).

Methods: This study consists of four studies, including 459 patients (278 receiving Cimlanod and 181 receiving placebo). The mean age was 63.9 years, 85% were male, and common comorbidities included hypertension (77%) and diabetes (45.7%). Outcomes were evaluated using risk ratios (RR) for binary end points and mean differences (MD) for continuous variables, with 95% confidence intervals (CI) and I² for heterogeneity. Study quality followed Cochrane methods. Primary outcomes included cardiovascular mortality, hemodynamic measures, and severe adverse events. The protocol was prospectively registered in PROSPERO (CRD420250652675; Feb 2025).

Results: Cimlanod did not significantly reduce all-cause mortality (RR = 0.96; 95% CI 0.88-1.04; p = 0.15), cardiac death (RR = 0.75; 95% CI 0.37-1.54; p = 0.43), adverse events (RR = 1.51; 95% CI 0.94-2.44; p = 0.073), or serious adverse events (RR = 0.83; 95% CI 0.46-1.48; p = 0.429), when compared with placebo. Although a significantly increased risk of symptomatic hypotension was observed with the use of Cimlanod (RR = 2.22; 95% CI 1.56-3.15; p < 0.01) but no significant effect on systolic or diastolic blood pressure or heart rate was observed in the pooled analyses, whereas significant drop in systolic blood pressure (SBP) (MD - 10.41, 95% CI - 19.89 to - 0.93) was observed with highest dose of Cimlanod i.e. 12 μcg/kg/min.

Conclusions: Cimlanod did not improve mortality, major hemodynamic end points, or biomarkers and increased the risk of symptomatic hypotension. Although a modest improvement in cardiac index was observed, evidence does not currently support routine clinical use, and further studies are required to identify whether any specific subgroup may benefit.

Registration: PROSPERO identifier number CRD420250652675.

Despite major advances with direct oral anticoagulants (DOACs), the clinical challenge of minimizing bleeding without losing efficacy remains unresolved. Factor XI (FXI) plays a pivotal role in thrombosis with limited contribution to hemostasis, making it an attractive target for novel anticoagulant therapy. Inhibition of FXI or its active form, FXIa, may therefore achieve effective antithrombotic protection while reducing the risk of bleeding. This review summarizes the biological rationale for targeting FXI, key pharmacological features of different inhibitor classes, and the main results from phase I-II trials of antisense oligonucleotides, monoclonal antibodies, and small-molecule FXIa inhibitors. It also discusses the ongoing phase III programs evaluating these agents across clinical settings, including atrial fibrillation, venous thromboembolism, and secondary prevention after acute coronary syndromes. Early phase studies have demonstrated robust and reproducible benefits in preventing venous thromboembolism after major orthopedic surgery, whereas efficacy in atrial fibrillation and secondary stroke prevention has been more variable. Key uncertainties persist regarding the most suitable indications, patient selection criteria, and how FXI inhibitors should be positioned alongside existing DOACs, particularly in high-bleeding-risk groups unsuitable for oral therapy, such as those with severe kidney failure, on dialysis, or facing cancer-related thrombosis.

Introduction: Antiplatelet therapy with low-dose aspirin, alone or as dual antiplatelet therapy (DAPT) with a P2Y₁₂ inhibitor, is used in secondary prevention following myocardial infarction (MI). However, the optimal duration of DAPT is unknown.

Methods: This cohort study performed in the French nationwide claims database compared 3-year outcomes between DAPT and low-dose aspirin alone pursued beyond 1 year after MI. All adults discharged from hospital following MI in 2013-2014, and who survived ≥ 1 year under DAPT, without rehospitalization for acute coronary syndrome or major bleeding were enrolled (N = 51,468). The primary outcome was a composite of MI, stroke, major bleeding, or all-cause death during the 3 years following the index date (defined as 365 days after MI). Secondary outcomes were a composite of MI, stroke, and all-cause death, and each component of the primary composite. DAPT and low-dose aspirin exposure periods were analyzed as time-dependent variables and compared using hazard ratios (HR) from Cox proportional hazard or Fine-Gray competing risks models, adjusted using a high-dimensional disease risk score.

Results: The 3-year cumulative follow-up duration was 93,398 person-years (DAPT exposure: 26,223 person-years; low-dose aspirin exposure: 67,175 person-years). HRs for DAPT versus low-dose aspirin were 0.93 (0.85-1.03) for the primary composite outcome, 0.93 (0.84-1.03) for the secondary composite outcome, 1.04 (0.87-1.25) for MI, 0.91 (0.70-1.17) for stroke, 1.19 (0.88-1.60) for major bleeding, and 0.94 (0.83-1.07) for death.

Conclusions: This national cohort study did not find a significant benefit of continued DAPT beyond 1 year after MI compared with low-dose aspirin.

Registration: This study was registered with the European Medicines Agency EUPASS registry ( https://catalogues.ema.europa.eu/catalogue-rwd-studies ; registration no. EUPAS29177).

Background: Randomized controlled trials (RCTs) have identified the additive effects of angiotensin receptor-neprilysin inhibitors (ARNIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors on neurohormonal inhibition therapy in patients with heart failure with reduced ejection fraction (HFrEF). However, their additive effects on conventional baseline therapies in patients with severe HFrEF remain unclear.

Methods: A systematic review was conducted using the PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases until February 2025. Our review included RCTs that evaluated the effects of ARNIs or SGLT2 inhibitors in patients with severe HFrEF. The primary outcome was the composite endpoint of cardiovascular death or hospitalization for heart failure. The pooled hazard ratio (HR) was estimated through a network meta-analysis conducted using a frequentist statistical approach.

Results: Five relevant trials, or their New York Heart Association class III-IV subgroups, were identified, comprising a total of 4894 patients with severe HFrEF. For the addition of SGLT2 inhibitors to neurohormonal inhibitors, the HR was 0.87 (95% confidence interval 0.75-1.01). For the addition of ARNIs, the HR was 0.96 (95% confidence interval 0.83-1.12). The certainty of evidence was moderate for SGLT2 inhibitors and low for ARNIs according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Conclusions: Evidence for the additive effects of SGLT2 inhibitors and ARNIs in severe HFrEF remains limited, and therefore, treatment intensification with these agents should be approached with caution.

Registration: International Prospective Register of Systematic Reviews (PROSPERO) identifier no. CRD42025641240.

Hypertension is one of the most frequent and consequential comorbidities in people with diabetes, yet its management remains less straightforward than guideline tables might suggest. Epidemiological evidence confirms the high prevalence and the disproportionate burden of cardiovascular and renal complications in this dual condition. The pathophysiology is complex: insulin resistance, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system (RAAS) interact, often with cumulative effects. Most recommendations endorse a blood pressure (BP) target below 130/80 mmHg, but whether strict numerical thresholds should dominate practice remains debated. Therapies such as RAAS inhibitors and sodium-glucose cotransporter-2 inhibitors demonstrate consistent benefits, extending beyond BP reductions. Given this multifactorial background, combination therapy carries a strong rationale, as it allows simultaneous targeting of multiple pathophysiological abnormalities. This article argues that success should be judged not only by BP values but by the outcomes that alter prognosis.