American Journal of Cardiovascular Drugs最新文献

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.

Introduction

Whether ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) carry distinct prognoses after discharge remains a matter of debate. This study aimed to compare 1-year clinical outcomes between patients with STEMI and NSTEMI in a large, real-world cohort.

Methods

Among 23,270 patients with acute coronary syndrome enrolled in the international PRAISE registry between 2003 and 2019, we included 21,789 patients with a diagnosis of either STEMI or NSTEMI. Clinical characteristics, discharge medications, and outcomes at 1 year were analyzed. The primary outcomes were all-cause mortality, re-infarction, and major bleeding. Multivariable logistic regression and propensity score matching were used to adjust for confounding. Subgroup and interaction analyses were also performed.

Results

The cohort included 12,365 patients with STEMI and 9424 patients with NSTEMI. At baseline, patients with NSTEMI had more comorbidities, cardiovascular risk factors (except diabetes), and prior revascularization. Patients with STEMI were more frequently treated with statins, beta-blockers, and renin-angiotensin-aldosterone system inhibitors at discharge. At 1-year follow-up, overall outcomes were comparable between groups. Nonfatal reinfarction occurred more frequently in patients with NSTEMI (3.4% versus 2.8%, p = 0.022), but this association was not significant after adjustment (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.65–1.24, p = 0.519). Results from propensity score-matched analyses confirmed the absence of prognostic differences. Subgroup analyses revealed significant interactions for diabetes mellitus and completeness of revascularization.

Conclusions

After accounting for clinical and therapeutic variables, 1-year outcomes were largely similar in patients with STEMI and NSTEMI. Differences in reinfarction risk appear to be driven by baseline characteristics and treatment patterns, rather than infarct type itself.

Objective

The aim was to systematically evaluate the effect of semaglutide on blood pressure in obese populations using meta-analysis methods.

Methods

Randomized controlled trials on the effect of semaglutide on blood pressure regulation published from the inception of the databases to October 2024 were searched for in PubMed, Embase, the Cochrane Library, and Web of Science. Stata software was used for statistical analysis of the outcome measures in all included studies. Egger’s test was applied to assess the risk of publication bias.

Results

A total of 22 studies involving 15,347 participants were included in this meta-analysis. The results showed that, compared to the control group, the semaglutide group significantly reduced systolic blood pressure (SBP) (mean difference [MD] − 2.90, 95% confidence interval [CI] − 3.70 to − 2.11; P < 0.01) and diastolic blood pressure (DBP) (MD − 0.86, 95% CI − 1.34 to − 0.38; P < 0.01). Further subgroup analysis revealed that, compared to diabetic populations, semaglutide had a more significant reduction in SBP (− 1.87, 95% CI − 2.67 to − 1.06, vs − 5.02, 95% CI − 6.10 to − 3.94) and DBP (− 0.43, 95% CI − 0.89 to 0.02, vs − 1.96, 95% CI − 3.12 to − 0.80) in non-diabetic populations. The higher dose of semaglutide (2.4 mg) was found to significantly lower SBP (MD − 4.31, 95% CI − 5.18 to − 3.44) and DBP (MD − 1.84, 95% CI − 2.70 to − 0.98), although mild heterogeneity was present. Sensitivity analysis showed that the exclusion of any single study did not significantly affect the final results.

Conclusion

Current evidence suggests that semaglutide can lower SBP and DBP, and increasing the dosage can enhance the blood pressure-lowering effect.