American Journal of Cardiovascular Drugs最新文献

The results of the recently concluded ULTIMATE-DAPT and T-PASS trials strongly support the emerging concept of antiplatelet monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention. Monotherapy with more potent antiplatelets such as ticagrelor is both a safe and an equally effective strategy to circumvent major bleeding episodes in patients at high bleeding risk while guarding against ischemic events. Although these results were not replicated with low-dose prasugrel monotherapy in the STOP-DAPT-3 trial, the other major trials investigating ticagrelor monotherapy (GLOBAL-LEADERS and TWILIGHT-ACS) suggested the feasibility and appropriateness of abbreviating the dual antiplatelet therapy (DAPT) as early as 1–3 months of the index procedure. Moreover, the recent data from TICO, T-PASS, and now the ULTIMATE-DAPT trial, hint toward early switchover to ticagrelor monotherapy without any undue concern of increased ischemic events. However, on closer examination, we find that study cohorts in most trials had lower anatomical complexity of coronary lesions and most adopted imaging-based revascularization strategies. Among these trials, those that achieved convincing levels of safety in ischemic endpoints mainly administered ticagrelor monotherapy. Can monotherapy with these newer antiplatelets sufficiently obviate the need for year-long DAPT? Can such antiplatelet monotherapy remain effective in all coronary artery disease subsets? Can we start patients solely on a single antiplatelet from day one of the procedure? These are some of the questions we attempt to answer by revisiting the results from these trials.

Finerenone is a novel nonsteroidal mineralocorticoid receptor (MR) antagonist (MRA) with unique pharmacological properties that offer potent and selective blockade of the MR with a more favorable side effect profile than spironolactone and eplerenone. In a large phase III clinical trial involving 13,026 patients with type 2 diabetes mellitus and a broad spectrum of chronic kidney disease, finerenone provoked a substantial placebo-subtracted reduction in the risk of hospitalization for heart failure (HF). These preliminary clinical trial data, along with the ongoing uncertainty about the safety and efficacy of MR antagonism in patients with HF and higher levels of ejection fraction have provided the rationale for the design of the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure) trial. In this multicenter, double-blind, randomized, phase III trial involving 6001 patients with HF and mildly reduced or preserved ejection fraction, finerenone was superior to placebo in improving the primary composite outcome of total (first and recurrent) worsening HF events and death from cardiovascular causes. This benefit was similar in magnitude in patients receiving and in patients not receiving background treatment with a sodium-glucose co-transporter type 2 inhibitor, suggesting a potential additive benefit with combination therapy. We explore the emerging role of the nonsteroidal MRA finerenone as a new therapeutic opportunity to improve the risk of adverse cardiovascular outcomes in patients with HF and mildly reduced or preserved ejection fraction. We discuss preliminary clinical trial data and provide a critical evaluation of the main results of the FINEARTS-HF trial.

Background and Objective

Evolocumab can reduce low-density lipoprotein cholesterol (LDL-C) levels and improve cardiovascular (CV) outcomes. While its benefits are well established in broader populations, its potential impact on patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) remains underexplored, particularly in real-world settings. This study aimed to evaluate its efficacy and safety in this specific patient group on the basis of real-world clinical experience.

Methods

A total of 384 patients with STEMI who underwent emergency PCI at Hebei General Hospital between 1 July 2021 and 23 September 2022 were enrolled in this retrospective, single-center study. Of these, 85 patients received evolocumab (140 mg every 2 weeks) plus standard of care (SOC), while 299 received SOC alone. Patients were monitored for CV events and lipid levels during follow-up. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were used to balance covariates.

Results

The experimental group had a lower cumulative incidence of the primary composite endpoint over 18 months in the unadjusted analysis (hazard ratio [HR] = 0.353; 95% confidence interval [CI] 0.180–0.693; P = 0.002), as well as after adjustment for PSM (HR = 0.341; 95% CI 0.165–0.706; P = 0.004) and IPTW (HR = 0.461; 95% CI 0.241–0.881; P = 0.019). The 18-month cumulative incidence was 10 (12%) for evolocumab + SOC and 95 (32%) for SOC. LDL-C levels in the evolocumab + SOC group showed significant reductions across different cohorts, compared with the SOC group. No significant differences in adverse events were observed between the two groups.

Conclusions

Evolocumab plus SOC significantly reduced postoperative CV events and LDL-C levels in patients with STEMI after emergency PCI.

Graphical Abstract

Background

Patients with adult congenital heart disease (CHD) have various indications for anticoagulation (e.g., presence of Fontan circuit, atrial fibrillation due to surgical scar). Guidelines recommend vitamin K antagonists (VKA) for thromboprophylaxis in adult CHD, as trial data comparing safety/efficacy of direct oral anticoagulants (DOAC) to VKA are not available in this population.

Methods

PubMed/MEDLINE, Embase, Web of Science, and Google Scholar were searched for trials comparing DOAC with VKA in patients with ACHD. Outcomes of interest were efficacy endpoints (thromboembolic complications) and safety endpoints (bleeding complications). Results were meta-analyzed and sensitivity analyses were performed.

Results

A total of 4 retrospective studies comprising 6004 patients (2566 DOAC, 3438 VKA) were analyzed. Compared with VKA, DOAC did not cause a statistically significant difference in incidence of thromboembolism (risk ratio, RR, 0.76; 95% confidence intervals, CI, 0.28, 2.07); composite bleeding (RR 1.02, 95% CI 0.71, 1.47); major bleeding (RR 1.05, 95% CI 0.92, 1.21); minor bleeding (RR 1.12, 95% CI 0.51, 2.44); or intracranial bleeding (RR 0.86, 95% CI 0.50, 1.46). Numerically, the DOAC arm had fewer thromboembolisms/intracranial bleeds but more major/composite bleeds. However, upon removal of the largest study, the DOAC arm had fewer major/composite bleeds.

Conclusions

DOAC did not confer a significant increase in either thromboembolic or bleeding risk as compared with VKA. Sensitivity analysis showed notable heterogeneity among studies. Large-scale trials comparing DOAC with VKA in patients with adult CHD are needed.

Background

Semaglutide has emerged as an effective medication for treating type 2 diabetes mellitus (DM). However, the cardiovascular effects and safety of this agent in patients with heart failure with preserved ejection fraction (HFpEF) are unclear.

Objective

This systematic review and meta-analysis aimed to assess the clinical and laboratory effects of semaglutide compared to placebo in patients with HFpEF.

Methods

We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and non-randomized cohorts, from inception to July 2024, comparing semaglutide versus placebo in patients with HFpEF. Statistical analyses were performed using R Studio 4.3.2. Mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were pooled across trials.

Results

This meta-analysis included three studies, two RCTs and one non-randomized cohort, reporting data on 1463 patients. The follow-up time of the studies was 52 weeks. Compared to placebo, the use of semaglutide was associated with a significant increase in the 6-min walk distance (MD 16.20; 95% CI 10.19–22.21; p < 0.01; I² = 0%). Additionally, reductions were observed in systolic blood pressure (MD −2.22; 95% CI −3.60 to −0.83; p < 0.01; I² = 0%), C-reactive protein level (MD 0.59; 95% CI 0.49–0.70; p < 0.01; I² = 51%), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels (MD 0.81; 95% CI 0.74–0.89; p < 0.01; I² = 0%).

Conclusion

These findings suggest that the use of semaglutide is associated with clinical and laboratory benefits in patients with HFpEF.

Flurpiridaz F 18 (FLYRCADO™) is an intravenous (IV) radioactive diagnostic drug being developed by GE Healthcare and Lantheus Medical Imaging for use in positron emission tomography (PET) myocardial perfusion imaging (MPI) to detect coronary artery disease (CAD). In September 2024, flurpiridaz F 18 was approved in the USA for PET MPI under rest or stress (pharmacologic or exercise) in adult patients with known or suspected CAD to evaluate for myocardial ischemia and infarction. This article summarizes the milestones in the development of flurpiridaz F 18 leading to this first approval for use in PET MPI in adult patients to evaluate for myocardial ischemia and infarction.

Oral bempedoic acid (NEXLETOL^® in the USA; Nilemdo^® in the EU) and the fixed dose combination (FDC) of bempedoic acid/ezetimibe (NEXLIZET^® in the USA; Nustendi^® in the EU) are approved to reduce cardiovascular (CV) risk in statin-intolerant patients who are at high risk for, or have, CV disease. A first-in-class therapy, bempedoic acid inhibits the adenosine triphosphate-citrate lyase enzyme in the cholesterol biosynthesis pathway. In the multinational phase III CLEAR Outcomes trial in statin-intolerant patients, once-daily bempedoic acid 180 mg significantly reduced the risk of the primary endpoint (a four-component major adverse CV event composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) compared with placebo. Bempedoic acid was generally well tolerated and, unlike statins, was associated with a low incidence of musculoskeletal adverse events (AEs). In conclusion, bempedoic acid as a monotherapy or adjunctive to other lipid-lowering therapies expands the treatment options available for the pharmacological reduction of CV risk in statin-intolerant patients, supporting achievement of low-density lipoprotein cholesterol (LDL-C) targets required for CV risk reduction.

Background

It remains controversial whether exercise training (EX) improves vascular endothelial function (VEF) independent of lipoprotein changes even though these are therapeutic goals for coronary artery disease (CAD).

Objective

The purpose of this study was to systematically review the effects of EX on VEF and blood lipid variables in patients with CAD.

Methods

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched five electronic databases (CINAHL, Embase, PubMed, SportDiscus, and Web of Science) until March 2024 for studies that met the following criteria: (i) patients with CAD aged ≥ 18 years; (ii) structured EX for ≥ 1 week in randomized or nonrandomized controlled studies; and (iii) measured brachial artery flow-mediated dilation (FMD) with or without blood lipid variables. We calculated effect sizes (ESs) and 95% confidence intervals (CIs) using a random-effects model and conducted subgroup analyses to identify the effect of training factors (duration, intensity, and weekly volume) on outcomes.

Results

In total, 11 studies with 19 trials (629 patients, 60 ± 9 years) met the inclusion criteria. We conducted a separate meta-analysis for each of the four outcome measures: FMD (13 ESs), high-density lipoprotein-cholesterol (HDL-C; eight ESs), low-density lipoprotein cholesterol (LDL-C; eight ESs), and triglycerides (TGs; eight ESs). EX significantly increased FMD (mean ES 0.57; 95% CI 0.44–0.70; P < 0.001) and HDL-C levels (mean ES 0.25; 95% CI 0.12–0.39; P < 0.001) but had no effect on LDL-C and TG. Subgroup analyses for FMD found no significant variation in effect by training factor (duration, intensity, and weekly volume).

Conclusion

EX improves VEF with increased HDL-C, but we found no changes in LDL-C and TG in patients with CAD, suggesting that HDL-C is preferentially associated with exercise-induced VEF improvement.

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) have demonstrated promising effects in lowering cardiovascular incidents among patients with acute coronary syndrome. However, their influence on early platelet reactivity after primary percutaneous coronary intervention (PPCI) remains unclear.

Objectives

This research sought to investigate the effects of entirely human anti-PCSK9 antibodies on platelet function as measured by thrombelastography and 12-month postoperative results in patients receiving PPCI and treated with ticagrelor-based dual antiplatelet therapy.

Methods

This single-center prospective study was conducted at Zhongshan Hospital, Fudan University, China, between January 2021 and June 2023. Patients were divided into two groups: those receiving standard statin therapy (statin-only group) and those receiving additional PCSK9 mAbs (either evolocumab 140 mg or alirocumab 75 mg, subcutaneously, every 2 weeks; PCSK9 mAb group). A total of 1250 eligible patients were enrolled. To equalize baseline characteristics, propensity score matching was conducted in a 1:1 ratio, resulting in 310 patients per group. Platelet activity was measured using thrombelastography 5 days after PPCI, presented as adenosine diphosphate-induced maximal amplitude (MA_ADP). The primary clinical outcome was the occurrence of major adverse cardiovascular events, which included cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization, measured over a 12-month period.

Results

At 5 days after PPCI, the PCSK9 mAb group exhibited levels of MA_ADP that were significantly lower than those in the statin-only group (17.10 ± 9.52 mm vs. 20.73 ± 12.07 mm, P < 0.001). The use of PCSK9 mAbs was significantly correlated with reduced MA_ADP (β − 0.166, P < 0.001). The occurrence of major adverse cardiovascular events in the PCSK9 mAb group was significantly lower than in the statin-only group. Furthermore, individuals in the top MA_ADP tertile (MA_ADP > 21.7 mm) plus statin-only subgroup exhibited the lowest rate of cumulative event-free survival.

Conclusion

Incorporating PCSK9 mAbs into ticagrelor-based dual antiplatelet therapy significantly reduced platelet reactivity and correlated with better cardiovascular results over a 12-month period. These findings support the use of PCSK9 mAbs as an effective adjunctive therapy in the management of acute coronary syndrome.

Around one-quarter of all patients undergoing cardiac procedures, particularly those on cardiopulmonary bypass, develop cardiac surgery-associated acute kidney injury (CSA-AKI). This complication increases the risk of several serious morbidities and of mortality, representing a significant burden for both patients and the healthcare system. Patients with diminished kidney function before surgery, such as those with chronic kidney disease, are at heightened risk of developing CSA-AKI and have poorer outcomes than patients without preexisting kidney injury who develop CSA-AKI. Several mechanisms are involved in the development of CSA-AKI; injury is primarily thought to result from an amplification loop of inflammation and cell death, with complement and immune system activation, cardiopulmonary bypass, and ischemia-reperfusion injury all contributing to pathogenesis. At present there are no effective, targeted pharmacological therapies for the prevention or treatment of CSA-AKI, although several preclinical trials have shown promise, and clinical trials are under way. Progress in the understanding of the complex pathophysiology of CSA-AKI is needed to improve the development of successful strategies for its prevention, management, and treatment. In this review, we outline our current understanding of CSA-AKI development and management strategies and discuss potential future therapeutic targets under investigation.