European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Cardiovascular disease (CVD) remains the leading global cause of morbidity and mortality. In addition to traditional risk factors, inflammation is established as a key mechanism in the initiation, progression, and complications of CVD. Elevated inflammatory biomarkers correlate with disease severity and adverse outcomes, prompting the evaluation of anti-inflammatory therapies in several cardiovascular settings. Colchicine has demonstrated potential in reducing cardiovascular events, though recent trial data have raised concerns regarding its overall benefit and optimal application after myocardial infarction. Alternative agents targeting inflammatory pathways-such as monoclonal antibodies against interleukins (e.g. canakinumab, tocilizumab, ziltivekimab)-have shown biological efficacy but are not yet approved for routine clinical use in CVD. Emerging strategies, including immune-modulatory therapies and RNA-based interventions, seek to achieve selective anti-inflammatory effects with reduced immunosuppressive risk. Future approaches will likely adopt personalized, multi-targeted regimens that integrate inflammation control with lipid-lowering and antithrombotic therapies. As evidence accumulates, inflammation may transition from an adjunctive target to a central focus in CVD management.

Aims: Ranolazine (Ran) is an anti-anginal drug inhibiting late sodium current, an action possibly hindering arrhythmias onset. Indeed, some evidence supports the anti-arrhythmic effects of Ran. The aim of this study, which evaluated Italian patients with chronic coronary syndrome (CCS), was to investigate whether Ran, as an add-on therapy, was associated with a lower incidence of atrial fibrillation (AF) compared with no-Ran prescription (No-Ran).

Methods and results: The original population (N = 6.1 million) derived from the databases of the Italian National Health System; information concerned hospitalizations with the related diagnoses, drug therapy, follow-up clinical events and visits. Patients hospitalized between 2011 and 2020 for any cause and discharged with an ICD-9-CM CCS code were studied if AF had not been diagnosed before. The follow-up duration was 4.4 and 5.0 years for the Ran and the No-Ran cohorts, respectively. Study subjects were 171 015 (mean age: 72 years; men: 66%; Ran: N = 22 207; No-Ran: N = 148 808). After propensity score matching, Ran (N = 6384) and No-Ran (N = 25 536) cohorts were similar for age, sex, comorbidities and drug therapy. AF incidence during follow-up was 5.3% and 9.6% in the Ran and in the No-Ran cohorts, respectively, with a 41% drug-related lower risk of arrhythmia development in the Cox model (HR = 0.59, 95% CI: 0.53-0.67, P < 0.001). Also, Ran correlated with reduced incidence of brady-arrhythmias (P = 0.001) and ventricular tachy-arrhythmias (P = 0.049), and with lower mortality (P < 0.001).

Conclusion: Our study, performed in a subset of the Italian CCS population, showed that Ran therapy was safe and associated with a long-term reduced AF incidence.

Type 2 diabetes mellitus typically has the lipid features of elevated trigycerides, reduced HDL-cholesterol (both parts of the metabolic syndrome) and average or slightly elevated LDL-cholesterol. In consequence of hypertriglyceridemia, LDL particles are small and dense and therefore highly atherogenic. Outcome studies reveal that LDL-C lowering drugs have an above-average efficacy in type 2 diabetes as compared with non-diabetic patients. A minor increase of glycaemia in statin trials does not impair the beneficial cardiovascular results. Non-statin lipid lowering drugs do not impair glycaemia. Type 2 diabetes mellitus is now considered a major indication for lipid lowering drugs, thus there is a high value of and no major limitation for those compounds.

Aims: Nonsteroidal mineralocorticoid receptor antagonists such as finerenone mitigate cardiorenal risks in patients with type 2 diabetes mellitus (T2DM). Real-world evidence comparing finerenone with spironolactone and eplerenone remains limited. This study aimed to evaluate the cardiovascular outcomes in T2DM patients treated with finerenone vs. spironolactone or eplerenone using real-world data.

Methods and results: A retrospective cohort analysis was conducted using the TriNetX US Collaborative Network database. Adult patients with T2DM who were newly prescribed finerenone, spironolactone, or eplerenone were included (2021-2024). One-to-one propensity score matching was applied to eligible participants, resulting in 2957 finerenone users matching with spironolactone users and 1603 finerenone users matching with eplerenone users. Cardiovascular outcomes, including major adverse cardiovascular events (MACEs), heart failure, and mortality, were assessed over 24 months of follow-up. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated using Cox regression models. Finerenone users had significantly lower rates of MACE compared with spironolactone users (HR: 0.53, 95% CI: 0.43-0.66) and eplerenone (HR: 0.66, 95% CI: 0.50-0.87). Mortality was also reduced with finerenone vs. spironolactone (HR: 0.45, 95% CI: 0.35-0.57) and eplerenone (HR: 0.56, 95% CI: 0.41-0.75). Heart failure events were fewer with finerenone than with spironolactone (HR: 0.70, 95% CI: 0.55-0.90) and eplerenone (HR: 0.70, 95% CI: 0.50-0.99). Differences in acute myocardial infarction and stroke rates were not statistically significant.

Conclusion: Finerenone demonstrated superior cardiovascular outcomes compared with spironolactone and eplerenone in patients with T2DM with significant reductions in MACE, mortality, and heart failure events.

Aims: To investigate the EQ-5D-3L Level Sum Score (LSS) in patients with heart failure (HF) and reduced (HFrEF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and the effect of sacubitril/valsartan on this score using patient-level data from the PARADIGM-HF and PARAGON-HF trials.

Methods and results: The LSS was calculated by summing the three levels (1-3) for each of the five domains (minimum sum score = 5; maximum sum score = 15). Patient characteristics and outcomes were compared across LSS tertiles (T1-T3) at baseline. Cox models were used to evaluate the primary endpoint [first HF hospitalization or cardiovascular death (CVD)] according to tertiles of LSS. Changes in LSS severity at 8 months were analysed using ordinal logistic regression models to estimate the effect of sacubitril/valsartan vs. enalapril or valsartan. Of 13 195 patients, 12 974 had a baseline LSS. Compared to lower LSS, patients with higher (worse) scores were older, more often women and White, and had more comorbidities and more severe HF. At 8 months, patients assigned to sacubitril/valsartan experienced more improvement and less worsening of LSS vs. the comparator: OR:1.16 (95%CI: 1.08-1.24). Sacubitril/valsartan also reduced the risk of the primary outcome across LSS tertiles: T1: HR: 0.87 (95%CI: 0.75-1.00); T2: 0.80 (95%CI: 0.71-0.90); T3: 0.87 (95%CI: 0.77-0.97); Pinteraction = 0.59. Higher LSS was independently associated with a greater risk of the primary endpoint, and the achieved LSS at 8 months may be more strongly associated with subsequent outcomes.

Conclusion: Sacubitril/valsartan significantly reduced the risk of HF events and improved health status across the LSS spectrum in HFrEF and HFmrEF/HFpEF.

Clinical trial registration: https://www.clinicaltrials.gov. Unique identifiers: NCT01920711 (PARAGON-HF), NCT01035255 (PARADIGM-HF).

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.