European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are effective in the long-term treatment of myocardial infarction with reduced left ventricular ejection fraction (LVEF). However, it is unknown whether there is a benefit in myocardial infarction with preserved LVEF (≥50%).

Methods and results: We used Swedish healthcare registries to emulate a target trial of ACEi/ARBs vs. no ACEi/ARBs for the prevention of a composite outcome (death, myocardial infarction, or heart failure) and its individual components among individuals under 75 years with myocardial infarction and LVEF ≥ 50% between September 2010 and June 2021. We estimated observational analogues of the intention-to-treat effect and the per-protocol effect with confounding adjustment via inverse probability weighting. The 10 697 individuals in the ACEi/ARB group were on average older (median 61 vs. 60 years) and more likely to be male (80.2% vs. 75.3% male) than the 4730 individuals in the no ACEi/ARB group. The estimated 5-year risk of the composite outcome was 7.8% (95% confidence interval 7.1%, 8.5%) in the ACEi/ARB group and 8.1% (7.0%, 9.3%) in the no ACEi/ARB group; risk difference -0.3% (-1.6%, 1.0%). After adjustment for adherence, the risk of the composite outcome was 6.5% (5.9%, 7.2%) in the ACEi/ARB group and 6.7% (5.6%, 8.1%) in the no ACEi/ARB group; risk difference -0.2% (-1.7%, 1.0%).

Conclusion: The estimated risk of a composite of death, myocardial infarction or heart failure was similar in recipients and non-recipients of ACEi/ARB. Our estimates suggest ACEi/ARB treatment in myocardial infarction with preserved LVEF does not confer a benefit.

Aims: The effect of initiating sacubitril/valsartan (Sac/Val) therapy during hospitalization for acute heart failure (AHF) on left ventricular (LV) remodelling remains unclear. This study aimed to assess the impact of Sac/Val on LV remodelling in patients in whom Sac/Val was initiated during AHF hospitalization.

Methods and results: This study was a sub-analysis of the Program of Angiotensin-Neprilysin Inhibition in Admitted Patients with Worsening Heart Failure (PREMIER) study, which investigated the impact of initiating Sac/Val during hospitalization for AHF on echocardiographic parameters over an 8-week period, in comparison with the standard renin-angiotensin system inhibitor therapy (control). Among the full analysis set of the PREMIER study, this analysis included 206 patients [mean age, 73 years; 64 females (31.1%)], who had available echocardiographic data. The Sac/Val group (n = 94) showed significantly improved LV function and morphological parameters at 8 weeks. Compared with the control group (n = 112), preload-dependent parameters improved significantly, including LV end-diastolic volume index [mean, -5.1 mL/m2; 95% confidence interval (CI), -10.2 to -0.04; P = 0.048] and tricuspid regurgitation peak velocity (mean, -0.17 m/s; 95% CI, -0.31 to -0.03; P = 0.016). In a subgroup analysis stratified by LV ejection fraction (LVEF), a reverse remodelling effect was primarily observed in patients with an LVEF < 40%.

Conclusion: Early Sac/Val initiation after hospitalization for AHF may significantly improve LV function and morphology at 8 weeks, particularly in patients with an LVEF < 40%, supporting its role in LV reverse remodelling.

Aims: While the beneficial effect of beta-blocker (BB) therapy for acute coronary syndrome (ACS) patients with a left ventricular ejection fraction (LVEF) of 40% is established, its role in those with LVEF > 40% is controversial. We assessed the relationship between BB therapy at discharge and 1-year mortality according to LVEF in a large contemporary acute coronary syndrome (ACS) cohort.

Methods and results: Patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry between 2005 and 2024 with information on BB at discharge, LVEF, and 1-year mortality were studied. The association between BB therapy and 1-year mortality and the interaction with LVEF (>40% vs. ≤40%) were analysed. Among 7820 patients (65% with ST-segment elevation myocardial infarction), 1570 (20.1%) had LVEF ≤ 40%. At discharge, 6211/7820 (79.4%) patients were on BB (LVEF > 40%, 78.1%; LVEF ≤ 40%, 84.5%). One-year mortality was higher in patients with LVEF ≤ 40% vs. >40% (7.1% vs. 2.3%; P < 0.001). Overall, BB therapy was associated with reduced mortality [unadjusted odds ratio 0.67 (95% confidence interval 0.51-0.89); P = 0.005]. Among patients with LVEF ≤ 40%, mortality was lower in patients with BB compared with those without (5.9% vs. 14%; P < 0.001). In contrast, in patients with LVEF > 40%, mortality did not differ between patients with and without BB (2.1% vs. 2.6%; P = 0.3). A statistically significant interaction between BB therapy and LVEF stratum was identified (pinteraction = 0.02).

Conclusion: Data from our large, nationwide registry suggest an overall benefit of BB therapy at discharge on 1-year mortality in ACS with most of the survival advantage observed in patients with LVEF < 40%.

Recurrent hyperkalaemia (HK) is associated with increased morbidity and mortality, and is common among patients with cardiorenal disease. Many of these patients require renin-angiotensin-aldosterone system inhibitor (RAASi) therapies that further enhance the risk of HK. Every acute HK episode constitutes an opportunity to treat and prevent recurrent HK. This report aims to support multidisciplinary team efforts in managing patients who may be affected by recurrent HK. A panel of nine European experts in the management of HK (four nephrologists, four cardiologists, one internist) reviewed existing guidance and evidence on the diagnosis and management of HK at a face-to-face (26th September 2023) and two virtual meetings (24th January and 14th March 2024). The panel developed 10 consensus recommendations and a management algorithm across three domains: duty of care, identifying patients at risk of HK recurrence and managing the risk of HK recurrence. Early identification and management of those at risk of recurrent HK will improve clinical outcomes but requires an interdisciplinary, co-ordinated approach. Disease-modifying therapies such as RAASi should no longer be considered reversible causes of HK, and efforts should be taken to up-titrate these to guideline-directed target doses even in the setting of an acute HK event. Every acute HK episode constitutes an opportunity to treat and prevent recurrent HK, contributing to long-term clinical benefits. The recommendations, intentionally broad in scope, complement existing management guidelines and plans, fostering a collective responsibility among healthcare professionals managing patients with HK.

There are sex-related differences (SRDs) in body composition, physiology, pharmacokinetics, efficacy, safety, and in dosage of some cardiovascular drugs. Thus, men and women may respond differently to certain drugs. However, information on SRDs in efficacy, safety, and dosage of cardiovascular drugs is scarce and their clinical relevance remains uncertain for two main reasons the traditional under-representation of women and drug efficacy and safety is not reported in a sex-disaggregated manner in randomized clinical trials (RCT). Thus, many RCTs were underpowered to analyse and detect SRDs, even if they do exist, and clinical practice guidelines (CPG) based on these RCTs recommend (with few exceptions) to treat women like men. Furthermore, women are less likely to receive CPG-recommended cardiovascular drugs (CPGRDs), present more adverse drug reactions, and may require lower doses of some drugs than men. In the era of 'precision medicine', this limited information should stimulate basic and clinical research to better understand the mechanisms underlying these SRDs in the efficacy and safety of CPGRDs because this represents the first step to develop a personalized pharmacotherapy. The aim of this narrative review is to analyse the reasons and consequences of the limited information on SRDs in efficacy, safety, and dosage of CPGRDs, to analyse whether the recommended doses are appropriate for women, to analyse the differences in the use of CPGRDs, and finally, to formulate recommendations to close our gaps in knowledge about SRDs and reverse the current situation to improve CVD prevention and treatment from a sex-specific perspective.

Aims: This study investigated the association between fenofibrate use and outcomes of heart failure (HF) in patients with Type 2 diabetes (T2D).

Methods and results: In a nationwide cohort database (2008-22) in South Korea, patients with T2D (≥30 years) receiving statin therapy were 1:1 matched by propensity score into a statin plus fenofibrate group (n = 11 722) and statin only group (n = 11 722). The primary outcomes were hospitalization for HF (HHF) and a composite of HHF or cardiovascular death. A Cox proportional hazards model was used to assess the association between treatments and outcomes. During a median of 50.4 months, the incidence rate per 1000 person-years of HHF was 3.44 and 4.13 in the statin plus fenofibrate and statin only groups, respectively (adjusted hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.65-0.98). The adjusted HR for the composite outcome of HHF or cardiovascular death was 0.79 (95% CI, 0.65-0.96). Sensitivity analyses limited to individuals with ≥80% adherence showed consistent results (HHF: adjusted HR, 0.63; 95% CI, 0.43-0.92; composite outcome: adjusted HR, 0.68; 95% CI, 0.48-0.97).

Conclusion: In this propensity-matched cohort study, the addition of fenofibrate to statins was associated with significantly lower risks of HHF and the composite outcome of HHF or cardiovascular death in patients with T2D, suggesting a novel cardiovascular benefit of fenofibrate.

Aims: Emerging evidence suggests sex-specific differences in platelet biology and clinical responses to antiplatelet agents. Light transmission aggregometry (LTA) represents the historical gold standard for the assessment of platelet reactivity but is influenced by pre-analytical and analytical variables. We analysed a large dataset of patients undergoing LTA using a standardized methodology to investigate the impact of sex on platelet reactivity with or without antiplatelet therapy.

Methods and results: Between 2004 and 2022, 11,913 patients sequentially underwent LTA assessments following stimulation with adenosine diphosphate (ADP) (2 µM), collagen (2 µg/mL), arachidonic acid (AA, 0.5 mM), and epinephrine (10 µM). After applying study entry criteria, 5687 patients were included: 428 healthy volunteers (HV, F = 273; M = 155), 1055 controls (CTR; F = 725; M = 330), 3289 aspirin-treated patients (ASA; F = 2058; M = 1231), 430 clopidogrel-treated patients (CLOP; F = 272; M = 158), and 485 patients on dual antiplatelet therapy (DAPT; F = 166; M = 319). Within each group, results were analysed and compared between males and females.Females exhibited significantly greater platelet reactivity in response to ADP compared to males in the HV (P = 0.004), CTR (P < 0.0001), ASA (P < 0.0001), and CLOP (P < 0.018) groups, but not in the DAPT group. Among aspirin-treated patients, females showed increased platelet reactivity (P < 0.0001) in response to collagen, compared with males.

Conclusion: Females exhibit heightened baseline ADP-dependent platelet reactivity and a diminished response to aspirin and clopidogrel monotherapy compared to males.