American Journal of Cardiovascular Drugs最新文献

Background

Cardiac myosin inhibitors (CMI) have emerged as the first disease-specific, noninvasive therapy with promising results in patients with hypertrophic cardiomyopathy. However, its role in obstructive hypertrophic cardiomyopathy (oHCM) remains uncertain, especially in secondary endpoints of randomized controlled trials (RCTs).

Methods

We systematically searched PubMed, Embase, Web of Science, and Clinicaltrials.gov from inception to June 2024 for RCTs comparing CMI versus placebo in patients with oHCM. We applied a random-effects model to evaluate efficacy and safety outcomes and primary or secondary outcomes of RCTs.

Results

We included five RCTs comprising 767 patients, of whom 402 (52.5%) were randomized to CMI. Relative to placebo, CMI were associated with a higher rate of improvement of at least one New York Heart Association (NYHA) functional class [risk ratio (RR) 2.33; 95% confidence interval (CI) 1.92–2.82]. In addition, CMI reduced resting left ventricular outflow tract (LVOT) [mean difference (MD) − 42.51 mmHg; 95% CI − 59.27 to − 25.75] and the provoked LVOT gradients (MD − 46.12 mmHg; 95% CI − 55.70 to − 36.54). However, CMI significantly increased the risk of reaching a left ventricular ejection fraction below 50% (RR 4.80; 95% CI 1.42–16.20), affecting 8% of patients during long-term follow-up of up to 120 weeks. There was no significant interaction across subgroups of class representatives, pointing to a class effect. The benefit-risk analysis indicated a larger benefit for NYHA class improvement than risk for systolic dysfunction.

Conclusion

In patients with oHCM, mavacamten and aficamten as a class improve clinical and hemodynamic endpoints compared with placebo, albeit with a higher incidence of a reduction in left ventricular ejection fraction.

Registration

PROSPERO CRD42023468079.

Introduction

Inadequate decongestion remains an unmet need in the management of patients with heart failure. The concept of door-to-diuretic (D2D) time to improve outcomes has been proposed for patients with heart failure (HF), but the trial results have been mixed.

Methods

We utilized Preferred Reporting Instrument for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) for scoping reviews with an extensive a priori search strategy for databases: PubMed and Scopus between January 2015 and November 2023. We used the key search terms “door-to-diuretic time” OR “door-to-furosemide time” OR “acute heart failure decongestion”. Early D2D time was defined as intravenous (IV) diuretic administration within 30–120 min of patient arrival to the healthcare facility. Articles were included if they met our criteria, were written in the English language, and investigated door-to-diuretic or furosemide time as a decongestive strategy to improve outcomes in patients with acute HF.

Results

From 588 articles, 13 articles fulfilled the inclusion criteria after excluding duplicates and articles that did not meet our inclusion criteria. Of these studies, there was 1 meta-analysis and 12 observational cohort/registry-based studies (10 were positive trials and 2 were neutral). The most common outcomes examined were mortality and rehospitalization with early diuretic administration. First, early treatment was associated with lower in-hospital mortality and shorter hospital length of stay. Second, higher doses of furosemide were associated with improved HF symptoms and decreased hospitalization, at the cost of transiently worsening renal function. Third, the evidence is mixed for long-term mortality benefits.

Conclusion

Although the impact of early D2D time on HF outcomes is mixed, early diuretic administration appears to be an effective and safe strategy that warrants further investigation in large-scale pragmatic comparative effectiveness trials. Future trials should consider utilizing diuretic efficiency-guided dose escalation and augmented diuresis using high-dose or combination diuretic therapy

Objective

This study aimed to investigate the safety of vericiguat in patients with coronary artery disease.

Methods

We conducted a comprehensive literature review of the PubMed, ClinicalTrials.gov, and Cochrane Library databases up to 27 March 2024. We included studies that compared vericiguat with placebo in patients with coronary artery disease. Clinical data were extracted, and adverse events were analyzed using Review Manager software (version 5.4) after conducting a quality assessment of the enrolled studies.

Results

Three randomized controlled trials involving 151 patients were included in this meta-analysis. Compared with the placebo group, vericiguat treatment resulted in a decrease in systolic blood pressure by 1.4–10 mmHg and diastolic blood pressure by 0.4–6 mmHg, along with an increase in heart rate by 1.8–7 bpm, all of which are clinically insignificant. Vericiguat treatment demonstrated no significant serious adverse events [odds ratio (OR) = 1.97; 95% confidence interval (CI) = 0.39–9.91; P = 0.41]. However, a significant difference in adverse events between the two groups was noted (OR = 4.04; 95% CI = 2.17–7.52; P < 0.001).

Conclusion

This meta-analysis suggests that vericiguat is a safe drug for use in patients with coronary artery disease; however, further clinical trials are needed to validate these findings.

Registration

The study protocol has been prospectively registered in PROSPERO (CRD42024528105).

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have become a first-line therapy for heart failure (HF) in adults. However, data on their use in HF associated with adult congenital heart disease (ACHD) are limited. This systematic review and meta-analysis evaluated the safety, tolerability, and efficacy of SGLT2is in ACHD HF patients, supplementing guideline-directed medical therapy.

Methods

A comprehensive systematic search and meta-analysis were conducted on studies examining SGLT2i use in ACHD HF patients. The primary endpoint was the change in the New York Heart Association (NYHA) functional class (FC), with secondary endpoints including changes in ventricular function and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Additionally, the safety and tolerability of SGLT2is were evaluated.

Results

The meta-analysis included eight studies with 287 patients aged 19–67 years (median age 37.5 years). Adding SGLT2is to combined therapies significantly improved NYHA FC (log odds ratio 1.3, 95% confidence interval [CI] 0.37–2.23, p = 0.01) and reduced NT-proBNP levels (mean difference [MD] −0.43, 95% CI −0.70 to −0.16, p < 0.001). A notable decrease in systolic blood pressure was observed (MD −0.32, 95% CI −0.51 to −0.14, p = 0.00). The adverse effect profile was comparable to that seen in routine HF, with fewer HF hospitalizations post-SGLT2i initiation. Urinary tract infections occurred in 14 patients (5%), with no instances of hypoglycemia or ketoacidosis reported. Medication withdrawal due to adverse effects was noted in 19 patients (7%).

Conclusions

SGLT2is are well tolerated in ACHD HF patients. Notably, SGLT2is improved NYHA FC and reduced NT-proBNP levels across a diverse ACHD HF patient cohort. However, further prospective, multicenter studies are needed to confirm the safety and efficacy of SGLT2is in this unique patient population.

Background

Emerging data on cardiovascular outcomes, specifically major adverse cardiovascular events (MACE), are being reported from various trials involving incretin mimetics, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and glucose-dependent insulinotropic polypeptide (GIP), especially among patients with obesity and diabetes. Our aim was to evaluate this matter, while also involving various traditional cardiovascular risk factors [e.g., several body weight (BW) parameters, blood pressure (BP), lipid profile].

Methods

A search of PubMed, Europe PMC, ScienceDirect, Cochrane, and ClinicalTrials.gov up to September 2024 was performed to identify GLP-1 RA and GIP trials in MACE risk reduction as a primary endpoint. Our secondary endpoints included a reduction in BW, waist circumference (WC), body mass index (BMI), BP changes, and lipid modifying effects, while also yielding safety concerns surrounding the use of these pharmaceutical agents. Mean differences (MD) and risk ratios (RR) were summarized using random-effects model.

Results

A total of 11 eligible randomized controlled trials (RCTs) comprising 8 GLP-1 RA trials and 3 dual GLP-1 RA/GIP (tirzepatide) trials were included. Compared with control groups, GLP-1 RA significantly reduced the MACE risk by 32% [RR 0.68 (95% CI 0.53–0.87); P = 0.002; I² = 73%, P-heterogeneity < 0.001] and 59% for tirzepatide [RR 0.41 (95% CI 0.18–0.92); P = 0.03; I² = 0%, P-heterogeneity = 0.96]. Incretin mimetics also substantially reduced BW, BP, and improved lipid panel measures. However, there was an increased risk of adverse events, specifically gastrointestinal disorders within the incretin mimetics subset.

Conclusions

Incretin mimetics have shown promise in reducing MACE risk while also enhancing cardiovascular risk factors, including blood pressure and lipid profile, in adults with obesity without diabetes.

Objective

This study aimed to systematically evaluate the regulation of low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin-kexin type 9 (PCSK9) with inclisiran using a meta-analysis.

Methods

A comprehensive search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted for randomized controlled trials of inclisiran published up to April 2024. Stata software was used for statistical analysis of outcome indicators from the included studies. Egger’s test was employed to assess the risk of publication bias.

Results

A total of 10 studies involving 5208 participants were included in this meta-analysis. The results indicated that inclisiran significantly reduced LDL-C levels (weighted mean difference [WMD] − 48.17%; 95% confidence interval [CI] − 51.78 to − 44.56%; P < 0.01) and PCSK9 levels (WMD − 77.91%; 95% CI − 82.99 to − 72.84; P < 0.01) compared with the control group. The incidence of adverse reactions in the inclisiran group did not differ significantly from that in the placebo group (relative risk [RR] 1.03; 95% CI 0.99–1.09; P = 0.15). Similarly, there was no significant difference in the incidence of cardiovascular adverse events between the inclisiran and placebo groups (RR 0.92; 95% CI 0.74–1.16; P = 0.49). Sensitivity analysis showed that the exclusion of any single study did not significantly affect the final results.

Conclusion

Current evidence suggests that inclisiran significantly lowers LDL-C and PCSK9 levels. The incidence of adverse events and cardiovascular adverse events was not significantly different from that with other drugs.

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are breakthrough agents for the treatment of type 2 diabetes mellitus (T2DM) and heart failure (HF). However, among patients with HF and T2DM, some uncertainty remains about individual comparisons, including dosing.

Objectives

We aimed to make a real-life individual comparison of SGLT2is among patients with HF and T2DM.

Methods

This was a subgroup analysis of the Turkish Ministry of Health’s National Electronic Database for adult patients with HF (TRends-HF). All-cause mortality (ACM) data up to 7 years were evaluated. Patients with HF and T2DM who were prescribed an SGLT2i were identified, and individual doses of empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg were compared. For individual comparisons, propensity score-matching analysis was generated as 1:1:1, and disease-modifying therapies (DMTs) for HF were considered.

Results

In the triple-matched cohort, 1-, 5-, and 7-year survival rates were 95%, 81%, and 76% versus 94%, 78%, and 72% versus 94%, 80%, and 75% for empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg, respectively. Among patients who were on triple DMT for HF, 1-, 5-, and 7-year survival rates were 95%, 78%, and 70% for empagliflozin 25 mg, 95%, 74%, and 66% for empagliflozin 10 mg, and 94%, 77%, and 69% for dapagliflozin, respectively. Annual emergency department visits were slightly lower with empagliflozin 10 mg and dapagliflozin 10 mg than with empagliflozin 25 mg. A greater proportion of patients on dapagliflozin 10 mg did not experience hospitalization during the 7-year follow-up compared with both doses of empagliflozin, albeit with a small effect size.

Conclusion

Among patients with HF and T2DM, SGLT2is are instrumental, and empagliflozin 10 mg remains significantly inferior to dapagliflozin 10 mg and empagliflozin 25 mg in terms of 5- and 7-year ACM.