American Journal of Cardiovascular Drugs最新文献

Heart failure is a major global health concern as it contributes to high rates of mortality and morbidity, with high rates of hospitalizations. The most prevalent risk factor or comorbidity of heart failure is obesity, which not only worsens and exacerbates disease progression and the course of illness, it also reduces its prognosis. Weight management is still not well addressed, even with major advancements in heart failure pharmacotherapies. Recent advances in weight-loss medications such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and other novel anti-obesity drugs have sparked interest in their potential to improve clinical outcomes for patients with heart failure, especially those who also have obesity-related cardiac dysfunction. Weight-loss medications benefit heart failure by reducing adiposity-related inflammation, myocardial stress, and remodeling. These effects are auspicious in heart failure with preserved ejection fraction, where obesity-driven mechanisms play a critical role. These medications have been demonstrated to help with weight reduction, improve heart failure symptoms, and reduce hospitalization rates. However, questions about their long-term safety, particularly in patients with severe heart failure, are still being researched. The purpose of this review is to summarize the current evidence on the safety and effectiveness of weight-loss medications in the treatment of heart failure, describe their mechanisms of action, and highlight knowledge gaps that require further research.

β-blockers are a fundamental component of cardiovascular disease (CVD) management, while β₂-agonists are used to treat chronic obstructive pulmonary disease (COPD). Current guidelines recommend that these conditions be treated as usual, even when they coexist. However, there have been concerns over COPD exacerbation risk with β-blockers and attenuation of the beneficial effects of β₂-agonists in this comorbid population, leading to β-blocker underuse. Recent evidence suggests that β-blockers, particularly cardioselective β-blockers, do not increase COPD exacerbations, demonstrate good efficacy and safety, and improve survival in patients with COPD after first-time myocardial infarction. In atrial fibrillation with COPD, both cardioselective and nonselective β-blockers may be associated with a lower COPD exacerbation risk than calcium channel blockers, as well as improving outcomes and reducing mortality risk. In this review, we summarize the β-blocker prescribing patterns in patients with CVD and COPD; describe the reasons for β-blocker underuse in patients with CVD with COPD; collate up-to-date evidence on the effects of β-blockers on symptoms and outcomes in each of these comorbid populations; and review the current treatment guidelines for coexisting COPD and CVD to support the rational prescribing of β-blockers. Finally, we provide recommendations for future research needed to demonstrate the clinical rationale of prescribing β-blockers and to encourage the generation of more robust evidence-based guidelines for β-blockers use. Future large-scale, prospective, randomized controlled trials are needed to expand the body of evidence and better understand the effects of β-blockers in CVD with comorbid COPD.

Aim

The aim of this study was to evaluate the efficacy of chronotherapy for patients with essential hypertension with a range of clinical characteristics.

Methods

We searched the PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials of antihypertensive therapies in which patients were randomized to morning or evening administration. The primary outcomes of the included studies were ambulatory blood pressure (BP) parameters and patient characteristics, including age, body mass index, percentage of female participants, and drug ingestion, which were described in subgroup analyses.

Results

In total, 56 studies were included in the analyses. Meta-analyses and subgroup analyses revealed that specific populations of patients benefited more from bedtime dosing than from morning dosing in both 24-h or 48-h ambulatory systolic BP (SBP) and nighttime SBP, including (1) groups aged < 60 years, (2) those with body mass index ≥ 30 kg/m², (3) studies with ≥ 50% female participants, and (4) patients receiving antihypertensive calcium channel blockers. However, when controversial data by Hermida et al. were omitted, the effects of BP controls were observed in patients with overweight, particularly obesity. Furthermore, calcium channel blockers contributed to an obvious reduction in nighttime SBP with chronotherapy.

Conclusions

Chronotherapy for hypertension may not be completely ineffective, and the clinical program and timing of medication administration can be selected according to the patient’s clinical characteristics.

Registration PROSPERO identifier number CRD42021292795.

Background

Oral anticoagulants (OACs) are recommended for stroke reduction in non-valvular atrial fibrillation (NVAF). OAC use has been studied in Medicare populations, but data for younger, commercially insured populations are limited.

Objective

This retrospective study aimed to describe the geographic variation of OAC use among commercially insured patients with NVAF at high risk of stroke (CHA₂DS₂-VASc score ≥ 2) in the USA.

Methods

Geographic variation was assessed by 3-digit zip code and race among patients identified from the Komodo Health commercial database with a diagnosis of NVAF between January 1, 2016, and August 31, 2021. Continuous health plan enrollment for ≥ 12 months before and 12 months after the NVAF diagnosis was required.

Results

A total of 619,111 patients with NVAF at high risk for stroke were identified, of whom approximately 50% were not treated with OACs. Of the half who received OACs, almost 85% received direct OACs (DOACs) and 15% received warfarin therapy. Overall, the highest untreated rates were observed in the South and West US regions, followed by the Midwest, then the Northeast. The highest DOAC treatment rates were in the Northeast for White patients and in the North and South for Black patients. The highest warfarin treatment rates were in the upper Midwest for White patients and the Midwest for Black patients.

Conclusions

This study may help guide the identification of areas to target interventions to improve treatment rates and confirm prior findings of geographic and racial variations of OAC use in NVAF.

Trimetazidine is a metabolic modulator that acts as a competitive inhibitor of the terminal enzyme in the β-oxidation pathway to shift energy substrate from free fatty acids to the more oxygen-efficient glucose metabolism. The resulting conservation of cellular adenosine triphosphate generation in the face of ischemia/hypoxia mediates the anti-ischemic efficacy of trimetazidine. Clinically, trimetazidine has been approved as an add-on treatment in patients with symptomatic angina that is poorly controlled with first-line agents or who cannot tolerate the first-line therapy. In addition, trimetazidine has demonstrated antioxidant, cytoprotective, and anti-apoptotic activity with applications beyond angina. The aim of this review was to summarize the mechanism of action and anti-anginal efficacy of trimetazidine and to discuss the putative role of these pleiotropic effects and the evidence behind its application in cardiovascular diseases in general.

Background

Tafolecimab is a novel PCSK9 inhibitor developed in China. In recently published phase III clinical trials, tafolecimab demonstrated long-term safety and efficacy in Chinese patients with hypercholesterolemia despite statin therapy. However, pharmacoeconomic studies of tafolecimab have yet to be published. This study aimed to explore the maximum cost-effective price of tafolecimab compared with statins alone for Chinese patients with hypercholesterolemia at various willingness-to-pay (WTP) thresholds.

Methods

A Markov cohort state-transition model was employed to assess the cost-effectiveness of tafolecimab from the perspective of the Chinese healthcare system. The low-density lipoprotein cholesterol (LDL-C) lowering effect of tafolecimab was observed in the CREDIT-4 trial. The baseline and subsequent incidence and transfer probability of cardiovascular events were based on prospective observational data in China and meta-analyses from the Cholesterol Treatment Trialists Study. Cost and utility values were obtained from the China Health Statistics Yearbook, health insurance, and published articles in China. The study also performed subgroup, sensitivity, and scenario analyses.

Results

The annual price thresholds for tafolecimab as an adjunctive therapy to statins were Chinese yuan (CNY) 3304 and CNY 7022 at WTP thresholds of CNY 89,358 and CNY 268,074 per quality-adjusted life year (QALY), respectively. The corresponding annual price thresholds for patients with hypercholesterolemia with acute myocardial infarction were CNY 10,355 and CNY 21,793 per year. Sensitivity analyses showed that the time horizon significantly impacted price thresholds, with a several-fold difference.

Conclusions

From the perspective of the Chinese healthcare system, the cost-effective annual price threshold for tafolecimab for patients with hypercholesterolemia was CNY 7022, at a threshold of CNY 268,074 per QALY.

Background

Patients with diabetes mellitus and its complications are at increased risk for cardiovascular diseases. Semaglutide is efficacious for glycemic control and reducing the risk of major adverse cardiovascular outcomes. Although trials have provided data about cardiovascular outcomes with this agent, a meta-analysis regarding its cardiovascular safety and variations in outcomes according to sex, race and estimated glomerular filtration rate was necessary.

Materials and Methods

We searched the PubMed, Cochrane Library, and Clinicaltrials.gov databases and included randomized controlled trials (RCTs) where semaglutide was the intervention and major adverse cardiovascular events (MACE) or expanded MACE was the outcome. We assessed the quality of the RCTs using the Cochrane Risk of Bias tool and used the statistical software RevMan 5.4. The protocol for this review was registered on PROSPERO (CRD42024580784).

Results

Of 5387 articles, four RCTs were included. The risk of MACE with semaglutide was significantly lower in patients with established or a risk of cardiovascular disease (risk ratio [RR] 0.81; 95% confidence interval [CI] 0.74–0.88; p < 0.00001). The risk of expanded MACE also reduced significantly with semaglutide (RR 0.80; 95% CI 0.75–0.86; p < 0.00001). MACE risk reduction was significant in males (RR 0.78; 95% CI 0.70–0.87; p < 0.00001) and in Asian (RR 0.61; 95% CI 0.44–0.83; p = 0.002) and white (RR 0.82; 95% CI 0.73–0.90; p = 0.0001) populations.

Conclusion

Semaglutide provides significant advantages in terms of lowering the risk of MACE and expanded MACE and could possibly be used as a crucial component of cardiovascular risk management, particularly in populations that respond well, such as men and Asian and white populations.

Registration

PROSPERO identifier number CRD42024580784.