American Journal of Cardiovascular Drugs最新文献

Introduction

The cardiovascular safety of testosterone-replacement therapy (TRT) for middle-aged and older men with low to low-normal levels of testosterone remains unclear.

Methods

We systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing TRT versus placebo for men aged ≥ 40 years old with hypogonadism or low to low-normal testosterone levels (≤ 14 nmol/L), and at least 12 months of follow-up. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) applying a random-effects model and using R version 4.3.1 for statistical analyses.

Results

We included 23 RCTs comprising 9280 men with testosterone deficiency, of whom 4800 (51.7%) were randomized to TRT. The mean age was 64.6 years, and the baseline total testosterone was 9.17 nmol/L. Placebo and TRT had similar rates of all-cause mortality (RR 0.85; 95% CI 0.60–1.19; p = 0.33). There was a significant increase in the incidence of cardiac arrhythmias (RR 1.53; 95% CI 1.20–1.97; p < 0.01). There was no significant difference between groups in cardiovascular mortality (RR 0.85; 95% CI 0.65–1.12; p = 0.25), stroke (RR 1.00; 95% CI 0.67–1.50; p = 0.99), and myocardial infarction (RR 0.94; 95% CI 0.69–1.28; p = 0.70).

Conclusion

In men with low to low-normal testosterone, aged 40 and above, TRT did not increase all-cause mortality, cardiovascular mortality, stroke, or myocardial infarction, but increased the incidence of cardiac arrhythmias.

Registration

PROSPERO identifier number CRD42024502421.

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown efficacy in reducing cardiovascular events in patients with diabetes mellitus (DM), but conflicting evidence exists regarding their impact on cardiac arrhythmias. Whereas some studies associated GLP-1RAs with arrhythmogenesis, other studies suggested a decreased association with atrial fibrillation (AF).

Objective

The aim was to compare the risk of incident AF after initiation of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is), as active comparators, in patients with DM.

Design

A retrospective propensity score-matched cohort study was conducted.

Setting

The national data of Veterans Health Administration during fiscal years 2006–2021 were used for the study.

Patients

Adults who initiated either GLP-1RA or DPP4i medications were included.

Measurements

The primary outcome was a composite outcome of AF (diagnosis of AF/flutter or undergoing an AF procedure).

Results

Out of 116,235 GLP-1RA users and 217,668 DPP4i users, we propensity score-matched 80,948 pairs, on 88 characteristics. The composite outcome of AF was similar in the GLP-1RA group (4.1%) and DPP4i group (4.3%); odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92–1.01. Secondary analyses stratified by medication use duration showed no significant differences in composite AF risk (p > 0.05). Individuals achieving 5% weight loss from baseline body weight had significantly lower AF incidence (OR 0.83, 95% CI 0.78–0.89), whereas no significant differences were observed in those with no weight loss or weight gain (OR 1.05, 95% CI 0.97–1.12).

Conclusions

GLP-1RA use was not associated with a decreased or increased risk of AF compared to DPP4i use. In subgroup analysis, lower AF risk was seen in GLP-1RA versus DPP4i users who achieved weight loss, which suggests weight loss as a potential modifier of response to GLP-1RAs.

Background

Chronic total occlusion (CTO) affects 15–25% of patients undergoing coronary angiography, and successful percutaneous coronary intervention (PCI) can improve ischemia, angina symptoms, and overall quality of life. However, CTO-PCI is a complex procedure with higher risks of acute thrombosis, restenosis, and long-term thrombosis due to factors such as longer lesion length, calcification, and the need for more stents. Dual antiplatelet therapy (DAPT) is essential after PCI, but the optimal regimen for CTO, particularly in patients with chronic coronary syndrome, remains under debate. Although more potent P2Y12 inhibitors such as ticagrelor may offer benefits in some cases, recent studies have shown mixed results.

Objective

This study aimed to assess the effect of potent DAPT on long-term outcomes in patients with CTO undergoing retrograde PCI.

Method

We conducted a retrospective analysis of 836 consecutive patients who underwent elective retrograde CTO-PCI at a single center between January 2011 and April 2023. We compared patient and lesion characteristics, procedural details and results, and long-term outcomes between patients who received ticagrelor and those who received clopidogrel after retrograde CTO-PCI.

Result

Clinical follow-up was available in 767 (91.2%) patients, with a median follow-up of 1041 days (range 531–1511). The risk of major adverse cardiovascular events was significantly lower in patients receiving ticagrelor than in those receiving clopidogrel (8.8% vs. 18.5%, p = 0.005), primarily due to reductions in all-cause mortality (1.9% vs. 8.1%, p = 0.009) and cardiac death (0.6% vs. 5.8%, p = 0.012).

Conclusion

DAPT with ticagrelor may represent a safe and efficient management strategy for patients undergoing retrograde CTO-PCI.

Hypertriglyceridemia has been proposed as a risk factor for atherosclerotic cardiovascular disease (ASCVD). Triglycerides (TG) are viewed as a marker for remnant cholesterol in triglyceride-rich lipoproteins, as this remnant cholesterol has been identified as a causal risk factor for ASCVD. The limited number of effective treatments for elevated TG has fueled the search for novel pharmacotherapy options, and multiple medication classes are being explored. Apolipoprotein C3 (APOC3) and angiopoietin-like protein 3 (ANGPTL3) are among the most promising targets. Several novel agents utilizing these pathways, including olezarsen, plozasiran, and zodasiran, are currently under development for the management of elevated TG, with olezarsen approved in 2024 for the management of familial chylomicronemia syndrome. This comprehensive review provides updated insights into the development of novel hypertriglyceridemia treatments.

Objective

Clinical trials have demonstrated the efficacy of the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in patients suffering from heart failure (HF), regardless of whether their left-ventricle ejection fraction (LVEF) is reduced (HFrEF), mildly reduced (HFmrEF), or preserved (HFpEF). This study aims to assess the cost-effectiveness of empagliflozin when added to standard of care (SoC), consisting of lifestyle changes, medications, and surgery or devices, compared to SoC alone in patients with chronic HF irrespective of LVEF in the Netherlands.

Methods

A Markov model was developed to simulate patient outcomes over a lifetime horizon, incorporating data from the EMPEROR-Reduced and EMPEROR-Preserved trials. Key outcomes included incremental cost-effectiveness ratios (ICERs) expressed in costs per quality-adjusted life-year (QALY) gained, life expectancy, and hospitalization rates. Probabilistic and one-way sensitivity analyses were conducted to assess the robustness of the results.

Results

The analysis revealed that treatment with empagliflozin plus SoC resulted in higher life expectancy (6.58 vs. 6.47 years for HFrEF; 7.78 vs. 7.69 years for HFmrEF/HFpEF) and a lower incidence of HF hospitalizations compared to SoC alone. The ICERs were €8515/QALY for HFrEF and €9807/QALY for HFmrEF/HFpEF, both below the willingness-to-pay threshold of €50,000/QALY, indicating cost-effectiveness. Sensitivity analyses confirmed the robustness of the results, indicating there is a high probability (97% for HFrEF and 98% for HFmrEF/HFpEF) that empagliflozin plus SoC is cost-effective.

Conclusion

Empagliflozin, when added to SoC, is a cost-effective treatment option for patients irrespective of LVEF in the Netherlands.

Introduction

Heart failure (HF) poses a significant public health burden in the USA and worldwide, with a higher incidence and disproportionate presentation at a younger age in Asian populations than in other racial and ethnic groups.

Objective

This study aimed to evaluate the treatment efficacy of different HF pharmacological interventions in Asian versus white patients with HF with reduced ejection fraction (HFrEF).

Methods

We conducted a pairwise meta-analysis of randomized controlled trials (RCTs) in adults with HFrEF. We searched the Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from inception to February 9, 2022. We identified RCTs investigating the efficacy of HF drugs, including angiotensin-converting enzyme inhibitors, an angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan), beta-blockers, hyperpolarization-activated cyclic nucleotide-gated channel blockers, sodium–glucose cotransporter 2 (SGLT2) inhibitors, renin inhibitors, vasopressin V2 receptor blockers, and oral soluble guanylate cyclase stimulators. The primary outcome was a composite endpoint of hospitalization of HF, cardiovascular death, and all-cause mortality.

Results

We included 11 RCTs involving 32,654 participants from Asian and white populations. In Asian patients, SGLT2 inhibitors (risk ratio [RR] 0.61; 95% confidence interval [CI] 0.49–0.75) were the most effective in reducing the composite endpoint of hospitalization of HF, followed by hyperpolarization-activated cyclic nucleotide-gated channel blockers (RR 0.62; 95% CI 0.42–0.89). In white patients, beta-blockers (RR 0.68; 95% CI 0.59–0.78) were the most effective in lowering the risk of adverse outcomes, followed by SGLT2 inhibitors (RR 0.72; 95% CI 0.53–0.97). Overall, SGLT2 inhibitors were the most effective treatment in reducing the risk of adverse outcomes among all patients with HFrEF (RR 0.72; 95% CI 0.53–0.97), with a better treatment effect in Asian patients than in their white counterparts (P_interaction = 0.014).

Conclusions

The findings from this study suggest that treatment with SGLT2 inhibitors is effective in lowering the risk of adverse clinical outcomes in patients with HFrEF for both Asian and white populations, with a more pronounced effect in Asian populations. These results highlight the importance of considering racial and ethnic differences in the management of HF.

Background

Ivabradine, a selective I_f current inhibitor, is widely prescribed for heart failure and chronic angina; however, its post-marketing safety profile across diverse clinical contexts remains underexplored.

Objective

This study analyzed ivabradine-associated adverse events (AEs) using the US Food and Drug Administration Adverse Event Reporting System, with a focus on overall patterns and indication-specific subgroups.

Methods

We reviewed reports from the US Food and Drug Administration Adverse Event Reporting System from quarter 2, 2015, to quarter 2, 2024, and conducted a disproportionality analysis using four methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. We stratified AEs by clinical indications (tachycardia, heart failure, coronary artery disease) and prioritized them using a semi-quantitative scoring system and important or designated medical event criteria as defined by the European Medicines Agency.

Results

A total of 2733 ivabradine-related AE reports were identified, involving 24 system organ classes. Cardiac disorders (n = 1045) and eye disorders (n = 352) were most frequent, with bradycardia, arrhythmias, and photopsia being the leading events. Subgroup analyses revealed distinct AE profiles: sinus tachycardia and supraventricular tachycardia in the tachycardia subgroup; blurred vision and angina in coronary artery disease; and severe AEs—such as dyspnea, prolonged QT interval, and ventricular fibrillation—primarily in heart failure. One rare but notable designated medical event, transient blindness (n = 3), was also identified.

Conclusion

Ivabradine shows an overall favorable safety profile. Most AEs appear related to underlying disease or comedications rather than intrinsic drug toxicity. These findings support indication-specific monitoring to enhance clinical safety and pharmacovigilance.

Objective

Obicetrapib, a selective cholesteryl ester transfer protein inhibitor in development for the treatment of dyslipidemia and cardiovascular risk, is expected to be administered with high-intensity statins in clinical practice. This study was performed to assess the effect of obicetrapib on the pharmacokinetics (PK) of atorvastatin and rosuvastatin.

Methods

An open-label study was conducted to evaluate the PK of atorvastatin 80 mg (cohort 1, n = 42) or rosuvastatin 40 mg (cohort 2, n = 32, non-Asians) with and without co-administration of 10 mg obicetrapib in healthy adult males and females. Study participants received statin on day − 4, obicetrapib on days 1–11, statin co-administered with obicetrapib on day 12, and obicetrapib on days 13–17. Blood samples were collected throughout the dosing period and analyzed for plasma obicetrapib (both cohorts); atorvastatin, ortho-hydroxy atorvastatin, and para-hydroxy atorvastatin (cohort 1), and rosuvastatin (cohort 2). Safety and tolerability were also assessed.

Results

The 90% confidence intervals of the geometric mean ratios for the log-transformed maximum plasma concentration and area under the curve from time 0 to the time of the last measurable concentration (AUC_t) and from time 0 to infinity (AUC_inf) for atorvastatin and rosuvastatin were all within the range pre-specified for bioequivalence (80.00–125.00%) of statin plus obicetrapib versus statin alone. Although there were significant treatment effects for atorvastatin AUC_t (p = 0.0026) and AUC_inf (p = 0.0012), the differences were small (9–10%) and not deemed clinically important. Overall, all study drugs were safe and well tolerated.

Conclusions

No clinically significant PK interaction occurred between multiple daily doses of obicetrapib on the single-dose PK of either atorvastatin or rosuvastatin in healthy volunteers.

Clinical Trial Registration

NCT06081166.