American Journal of Cardiovascular Drugs最新文献

Background and Objective

Left atrial strain (LAS) has prognostic value in patients with atrial fibrillation (AF). Consequently, therapies that improve LAS may help reduce AF-related adverse cardiac events. We aimed to compare how digoxin and bisoprolol modulate LAS in patients with AF being treated with rate control.

Methods

This was a bicentric randomized controlled trial. Patients with AF, naïve to beta-blockers and digoxin, and scheduled for treatment with a rate control strategy were randomized to receive oral bisoprolol 5–10 mg daily or digoxin 0.25 mg daily. The primary aim was to compare the change in peak LAS before and after 30 days of treatment between the two groups.

Results

A total of 60 patients, equally distributed between the two groups, completed the trial. By day 30, there was no significant difference in global peak LAS between the groups. However, when analyzed separately, the two-chamber view showed a significantly higher peak LAS in the digoxin group than in the BB group (mean 7.5 ± standard deviation 3.2% vs. 5.9 ± 3.4%; p = 0.004). Similarly, the four-chamber view also showed a higher peak LAS in the digoxin group (7.2 ± 3.6% vs. 6.4 ± 3.8%; p = 0.047). Considering the entire LAS curve rather than solely the peak value, digoxin significantly increased all LAS curves. In the global and four-chamber view, the digoxin maximum effect occurred significantly earlier than the peak of the LAS curve (p < 0.001). This effect remained constant over the cardiac cycle in the two-chamber curve (p < 0.001).

Conclusion

Our findings suggest that, in patients with rate-controlled AF, digoxin positively modulates LAS when compared with bisoprolol.

Clinical Trials Registration Number

NCT05540600, https://clinicaltrials.gov.

Nicotinamide adenine dinucleotide (NAD⁺) is a promising anti-aging molecule that plays a role in cellular energy metabolism and maintains redox homeostasis. Additionally, NAD⁺ is involved in regulating deacetylases, DNA repair enzymes, inflammation, and epigenetics, making it indispensable in maintaining the basic functions of cells. Research on NAD⁺ has become a hotspot, particularly regarding its potential in cardiovascular disease (CVD). Many studies have demonstrated that NAD⁺ plays a crucial role in the occurrence and development of CVD. This review summarizes the biosynthesis and consumption of NAD⁺, along with its precursors and their effects on raising NAD⁺ levels. We also discuss new mechanisms of NAD⁺ regulation in cardiovascular risk factors and its effects of NAD⁺ on atherosclerosis, aortic aneurysm, heart failure, hypertension, myocardial ischemia–reperfusion injury, diabetic cardiomyopathy, and dilated cardiomyopathy, elucidating different mechanisms and potential treatments. NAD⁺-centered therapy holds promising advantages and prospects in the field of CVD.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C. In 2021, inclisiran, a small interfering ribonucleic acid (siRNA) molecule targeting PCSK9 was approved by the Food and Drug Administration (FDA). Inclisiran has demonstrated effective reductions of LDL-C, such as in the large phase-3 ORION-9, ORION-10, and ORION-11 trials in which it achieved LDL-C reductions of 39.7%, 52.3%, and 49.9%, respectively. This review discusses the current clinical evidence and ongoing clinical studies of inclisiran as well as analyzes other areas of PCSK9 inhibition development.

Background

Morphine is used to control pain in ST-elevation myocardial infarction but reduces P2Y12 inhibition. It is not known if this modulation of platelet inhibition appreciably affects clinical outcomes.

Methods

We screened 979 articles and identified seven studies that met the eligibility criteria for meta-analysis. Outcomes included 11 metrics across angiographic and clinical domains. A random effects model assessed heterogeneity between studies.

Results

The opiate group showed decreased achievement of postprocedural thrombolysis in myocardial infarction (TIMI) 2 flow relative to placebo [risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52–0.97, p = 0.03, I² = 0.0%]. All other metrics listed below showed no statistically significant difference between groups: infarct size, microvascular obstruction, microvascular/salvage index, absence of pre- percutaneous coronary intervention (PCI) TIMI 3 flow, postprocedural TIMI 2 flow, postprocedural TIMI 3 flow, all-cause mortality, stroke, repeat MI, unstable angina, and left ventricular ejection fraction. However, there were no statistically significant differences in infarct size [odds ratio (OR) − 0.12, 95% CI − 0.37 to 0.17, p = 0.42], microvascular obstruction [standard mean difference (SMD) = 0.02, 95% CI − 0.12 to 0.16, p = 0.82], microvascular obstruction/salvage index (SMD = − 0.05, 95% CI − 0.24 to 0.13, p = 0.57), absence of pre-PCI TIMI 3 flow (OR 0.98, 95% CI 0.79–1.22, p = 0.87), and postprocedural TIMI 3 flow (OR 1.23, 95% CI 0.84–1.79, p = 0.28) between the two groups.

Conclusions

In STEMI, opiates correlate with worse angiographic outcomes, specifically postprocedural TIMI 2 flow. However, this observation does not appear to be clinically consequential.

Background

CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective

Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods

Eligible CVAEs were extracted from the ClinicalTrials.gov registry. A systematic search of electronic databases (PubMed, Embase, Cochrane Library, and important meetings) until 3 September 2023 was conducted. A disproportionality analysis was performed from the first quarter (Q1) of 2013 to Q1 of 2023 using data from the FAERS database. Study heterogeneity was assessed using the I² statistic. Using Peto odds ratio (Peto OR) and inverse variance methods to calculate the risk and incidence of CVAEs associated with CDK4/6 inhibitors.

Results

In total, 17 RCTs with 23,437 patients were included in our meta-analysis. During the follow-up period of 8.4–34.0 months, CDK4/6 inhibitors significantly increased the risk of CVAEs (Peto OR, 1.86, 95% confidence interval, 1.30–2.68, P < 0.01). The rates of hypertension and QT prolongation were 68.07 (62.87–73.27) and 57.15 (50.83–63.48) per 1000 patients, respectively. Moreover, we identified nine CVAEs that were not reported in RCTs. These included acute coronary syndrome, arrhythmia, lymphoedema, hot flush, vein rupture, thrombophlebitis migrans, embolism venous, angiopathy and intracardiac thrombus, which were found to be strongly correlated with CDK4/6 inhibitors. Furthermore, the risk of CVAEs varied depending on the specific CDK4/6 inhibitors used, its combination with different endocrine therapies, and the patient's treatment stage.

Conclusion

CDK4/6 inhibitors increase the risk of CVAEs, some of which may lead to serious consequences. Early recognition and management of CVAEs is of great importance in clinical practice.

Registration

PROSPERO registration number CRD42023462059.

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).