American Journal of Cardiovascular Drugs最新文献

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: Early neurological deterioration (END) in patients with acute ischemic stroke (AIS) is a common phenomenon strongly associated with unfavorable outcomes. The TREND trial (NCT04491695) demonstrates the efficacy of intravenous tirofiban compared to oral aspirin in preventing END.

Aims: The purpose of this study was to explore whether prior antiplatelet therapy (APT) affected the therapeutic effects of tirofiban.

Methods: This prespecified post hoc analysis of the TREND trial stratified patients by prior antiplatelet use. The primary outcome was END₄ (≥ 4 points increase in National Institutes of Health Stroke Scale [NIHSS] within 72 h). Secondary outcomes included END₂ (≥ 2 points increase in NIHSS), early neurological improvement, 90-day functional outcomes, and safety events.

Results: Overall, 425 patients with AIS were analyzed, including 143 (33.6%) and 282 (66.4%) with and without prior APT, respectively. In patients without prior APT, tirofiban significantly reduced the risk of END₄ compared with aspirin (5.0% versus 14.2%; adjusted OR, 0.38; 95% CI 0.15-0.96; P = 0.040). Tirofiban was beneficial in reducing the risk of END₂ in both patients with (8.3% versus 22.5%, P = 0.020) or without prior APT (13.5% versus 24.1%; P = 0.032). There was no significant interaction between treatment and prior APT status (P for interaction > 0.05). Further, no significant differences in 90-day functional outcomes or safety events were observed between the treatment groups for either antiplatelet status after adjustment.

Conclusions: Intravenous tirofiban significantly reduced the risk of END compared with aspirin in patients with AIS who were not on prestroke APT. Although this benefit was attenuated in pretreated patients, tirofiban might maintain a consistent efficacy and safety profile irrespective of prior antiplatelet use.

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.

Cardiac sarcoidosis (CS) is an elusive, yet potentially life-threatening disease marked by granulomatous inflammation of the myocardium, which can lead to arrhythmias, heart failure, and sudden cardiac death. Although corticosteroids have long been the mainstay of treatment, the therapeutic landscape is rapidly evolving. Recent insights have underscored the role of alternative immunosuppressants and biologic agents in enhancing disease control while minimizing long-term toxicity. Advances in imaging, particularly cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) are transforming both diagnosis and follow-up, enabling earlier detection and personalized monitoring of therapeutic response. At the same time, arrhythmia management and device implantation, especially implantable cardioverter-defibrillators (ICDs), have become central to risk stratification and prevention of fatal outcomes. This review explores the latest developments in the management of CS, highlighting a paradigm shift toward integrated, multidisciplinary care. From immunomodulation to advanced imaging and electrophysiological strategies, we emphasize the importance of tailoring interventions to disease severity and patient risk. Special focus is given to high-risk cases and evolving criteria for heart transplantation, grounded in the most up-to-date clinical evidence.

Aims: Residual cardiovascular risk remains substantial in patients with atherosclerotic cardiovascular disease (ASCVD) despite high-intensity statin therapy. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies and small-interfering RNA agents, offer additional risk reduction, yet comparative evidence across individual regimens remains limited.

Methods and results: We conducted a systematic review and network meta-analysis of randomized controlled trials evaluating approved PCSK9i dosages in patients with ASCVD. The primary outcome was major adverse cardiovascular events (MACE); the secondary outcomes included myocardial infarction, stroke, coronary revascularization, cardiovascular mortality, and all-cause death. A total of eight trials involving 49,847 patients were included. Evolocumab (140 mg every 2 weeks or 420 mg monthly) and alirocumab 150 mg every 2 weeks significantly reduced MACE compared with placebo (risk ratios (RR): 0.78, 95% confidence intervals (CI): 0.66-0.93 and RR: 0.47, 95% CI 0.25-0.86, respectively). Evolocumab was also associated with reductions in myocardial infarction, stroke, and revascularization. Alirocumab 150 mg demonstrated the most pronounced effect on revascularization and was superior to both evolocumab and the lower alirocumab dose in this outcome. No regimen significantly reduced cardiovascular or all-cause mortality.

Conclusions: These findings suggest that PCSK9 inhibitors are effective in ASCVD, with generally similar efficacy across agents; however, regimens achieving lower and sustained low-density lipoprotein cholesterol levels may confer greater benefit, in line with the concept that "the lower, the better."

Trial registration: PROSPERO identifier no. CRD420251022108.

Background: Cardiac involvement in sarcoidosis can manifest as new-onset heart failure (HF) due to inflammatory dilated cardiomyopathy (sarcoid cardiomyopathy [SCM]), conduction abnormalities, ventricular arrhythmias, and sudden death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to improve HF outcomes and reduce mortality. Current guidelines endorse dapagliflozin and empagliflozin for HF management. However, their role in SCM is not known. This study evaluates SGLT2 inhibitors in patients with sarcoid cardiomyopathy and reduced left ventricular ejection fraction (LVEF).

Methods: We utilized the TriNetX research network database from which we formed a cohort of patients with established SCM and a LVEF of less than 50%. Patients were divided into two groups on the basis of the presence or absence of SGLT2 inhibitors in their medical regimen. We analyzed the data for 12-month outcomes, including all-cause mortality, all-cause hospitalization, and HF hospitalization.

Results: Propensity score matching yielded a total of 636 subjects with balanced baseline characteristics. Mean age was 60 ± 12 years, and 37% were female individuals. At 12 months, SGLT2 inhibitor use was associated with lower all-cause mortality (4.1 versus 8.8%, hazard ratio [HR] = 0.46, p = 0.019), total hospitalizations (HR = 0.79, p = 0.043), and HF hospitalizations (HR = 0.67, p = 0.016). Use of SGLT2 inhibitors was associated with a significant reduction in arrhythmic events (ventricular tachycardia, fibrillation, cardiac arrest, and second- or third-degree heart block) (HR = 0.59, p = 0.007) along with an improvement in LVEF.

Conclusions: SGLT2 inhibitor use is associated with improved outcomes in SCM with reduced LVEF, including lower mortality, hospitalization, and incidence of arrhythmic events. Our data support the use of SGLT2 inhibitors in this specific HF population.