European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: The optimal short-term antithrombotic strategy following left atrial appendage occlusion (LAAO) remains uncertain, with the need to balance thromboembolic prevention and bleeding risk presenting a critical challenge. Recent evidence suggests that direct oral anticoagulants (DOACs) may provide a favourable safety-efficacy profile, with low-dose regimens showing potential benefits during the device endothelialization period. This network meta-analysis (NMA) aimed to compare the efficacy and safety of various antithrombotic strategies, including DOAC dosing, following LAAO.

Methods and results: A systematic review and NMA were conducted following Cochrane and PRISMA guidelines. Eligible studies included randomized controlled trials (RCT) and observational studies comparing at least two antithrombotic regimens in patients with non-valvular atrial fibrillation undergoing percutaneous LAAO. Primary outcomes were major bleeding and thromboembolism. Secondary outcomes included device-related thrombosis (DRT) and all-cause mortality. Pairwise and network meta-analyses were performed using a random-effects model. A total of 52 studies (49 observational and 3 RCTs) involving 69 751 patients were included. DOACs were consistently associated with significantly lower rates of major bleeding and all-cause mortality than other antithrombotic regimens. Low-dose DOACs showed a potential advantage over standard-dose DOACs in reducing major bleeding risk (odds ratio 0.45, 95% confidence interval: 0.22-0.92). For thromboembolism and DRT, standard-dose DOAC significantly reduced risk compared with single antiplatelet therapy (SAPT) but not with dual antiplatelet therapy (DAPT), whereas low-dose DOAC significantly reduced both outcomes compared with SAPT, DAPT, and vitamin K antagonists plus SAPT. In ranking analysis, DOACs emerged as the most effective and safest antithrombotic strategy, with low-dose DOACs demonstrating further safety benefits in bleeding outcomes.

Conclusion: DOACs provide a superior safety-efficacy profile compared with other antithrombotic strategies following LAAO, significantly reducing the risks of major bleeding, thromboembolic events, and mortality. While low-dose DOACs may offer additional bleeding risk reduction without compromising efficacy, further research is warranted to confirm their role in clinical practice.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a novel class of medications promising for treating cardiovascular disease or obesity, while concerns regarding their potential gastrointestinal adverse events persist. In our study, we report that genetically proxied GLP-1RAs may increase risk of acute pancreatitis but not other gastrointestinal adverse events.

Aims: Several diuretic strategies, including furosemide i.v. boluses (FB) or continuous infusion (FC), are used in acute heart failure (AHF).

Methods and results: We systematically searched phase 3 randomized clinical trials (RCTs) evaluating diuretic regimens in admitted AHF patients within 48 h and irrespective of clinical stabilization. We calculated the odds ratio (OR) of FC or FB plus another diuretic (sequential nephron blockade, SNB) compared to FB alone on 24 h weight loss (WL) and worsening renal function (WRF), with a random-effects model with inverse variance weighting. Urine output, hypokalaemia, hyponatremia, and all-cause mortality/rehospitalization were secondary endpoints. In 25 selected RCTs (7149 patients, mean age 68.9 ± 8.7 years, mean left ventricular ejection fraction 38.2 ± 10.7%), FC [OR 1.55 (95% confidence interval 1.39-1.63)], FB plus tolvaptan [OR 1.57 (1.39-1.77)], FB plus SGLT2i [OR 1.23 (1.06-1.42)], and FB plus thiazide [OR 1.63 (1.37-1.94)] were associated with greater WL than FB. FB plus SGLT2i [OR 1.52 (1.19-1.94)] and FB plus acetazolamide [OR 1.81 (1.31-2.49)] were associated with WRF. FB plus thiazide was associated with both WRF [OR 1.78 (1.43-2.21)] and hypokalaemia [OR 1.69 (1.32-2.16)]. Results were consistent in sensitivity analyses considering urine output, RCTs protocol-established furosemide doses, or daily furosemide dose. Congestion/decongestion scores and clinical outcomes were reported in around 50% of RCTs. In an underpowered exploratory analysis, mortality/rehospitalization was non-significantly lower with SGLT2i [OR 0.45 (0.19-1.07)].

Conclusion: FC and SNB improve surrogates of response to FB in AHF. SNB is also connoted by WRF and may induce hypokalaemia. The endpoints of diuretic RCTs should be revised and harmonized.

Background and aims: Extended dual pathway inhibition (DPI) with aspirin and rivaroxaban is recommended in high-risk patients with chronic coronary syndrome (CCS). In the 2024 update of the European Society of Cardiology guidelines on CCS, the high-risk criteria were revised. In the COMPASS cohort, we evaluated net clinical benefit of DPI according to baseline risk as defined by the ESC criteria in CCS patients.

Methods: CCS patients randomized to aspirin alone or DPI (n=15,429) were risk stratified using the 2024 ESC criteria. Endpoints included major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month absolute risk difference combining MACE and bleeding.

Results: High-risk status was associated with higher 30-month incidences of MACE (6.4% vs. 5.0%, HR 1.33, 95% CI 1.09-1.63) and composite adverse events (7.1% vs. 5.7%, HR 1.31 [1.09-1.58]), but not all-cause death or bleeding. DPI reduced MACE (low-risk: HR 0.66 [0.45-0.95]; high-risk: HR 0.77 [0.66.-0.91]; p-value for interaction 0.42) and all-cause death (low-risk: 0.78 [0.53-1.14]; high-risk: HR 0.78 [0.64-0.94], p-value for interaction 0.99). DPI provided similar net clinical benefit in low-risk (30-month risk difference -1.77% [-3.88-0.33], HR 0.79 [0.56-1.11]) and high-risk patients (30-month risk difference -2.06% [-3.20--0.91], HR 0.80 [0.69-0.93]; p-value for interaction 0.94).

Conclusions: In CCS patients, DPI reduced all-cause death and MACE while increasing major bleeding. The 2024 ESC criteria performed poorly in terms of distinguishing patients at high vs. low ischemic risk, making them inadequate to provide guidance for DPI use.

Background: Immune-related adverse events(irAEs) are common among cancer patients receiving dual immune checkpoint inhibitors (ICI). Cardiac adverse events rank among the most severe categories of such reactions. This study aims to investigate the characteristics and influencing factors of cardiac adverse events associated with dual ICIs.

Methods: We collected data on cardiac adverse events associated to dual ICIs from the U.S. Food and Drug Administration Adverse Event Reporting System database (FAERS), covering the period from the first quarter of 2015 to the fourth quarter of 2024. A disproportionality analysis was performed to assess the association between different dual ICIs and cardiac adverse events, and a comprehensive study was conducted to identify potential influencing factors.

Results: Cardiac adverse events accounted for 7.5% of all ICI adverse event reports in the FAERS database. Nivolumab plus ipilimumab was associated with the highest number of significant PT (Preferred Term) signals, while durvalumab plus tremelimumab had the highest percentage of life-threatening outcomes. The median onset time for cardiac adverse events following dual ICIs therapy was 32 days (IQR 15-77). Myositis and myasthenia gravis were the most commonly co-reported extracardiac conditions in myocarditis cases, whereas complete atrioventricular block and cardiogenic shock were the most frequently reported intracardiac complications. Older patients, males, and those with kidney cancer were at higher risk of developing cardiac adverse events.

Conclusions: This study identified distinct associations between different dual ICIs treatment strategies and various cardiac adverse events. We further identified potential risk factors and co-reported symptoms of cardiotoxicity, which may aid in the early diagnosis and monitoring of ICI-associated cardiac adverse events.

Background and aims: Current guidelines recommend beta-blocker therapy after myocardial infarction (MI) regardless of left ventricular ejection fraction (LVEF). However, recent trials question their benefit in patients with preserved LVEF. No study has yet compared beta-blocker effects during the acute coronary syndrome (ACS) phase (≤1 year post-MI) versus the chronic coronary syndrome (CCS) phase (>1 year).

Methods: In this pre-specified landmark analysis of the REBOOT trial, we evaluated the effect of beta-blocker therapy on outcomes in two post-MI phases: the ACS period (first year; cohort 1, n = 8,438) and the CCS period (>1 year, event-free patients with follow-up; cohort 2, n = 7,783). The primary endpoint was all-cause death, nonfatal reinfarction, or heart failure hospitalization; secondary endpoints included individual and additional cardiovascular events.

Results: Among 623 primary outcome events, 238 occurred in the first year (28.9/1,000 patient-years) and 385 thereafter (19.3/1,000 patient-years). Secondary prevention use was generally high, but patients with early events had lower prescription rates than those with late events or no events. Beta-blockers were not associated with lower risk of the primary or component outcomes in either phase. A nonsignificant trend toward benefit of beta-blockers appeared during the first year in patients with mildly reduced LVEF (41-49%), whereas in the CCS phase, higher beta-blocker doses were associated with worse outcomes.

Conclusions: In invasively treated MI patients with LVEF >40%, beta-blockers did not reduce adverse outcomes in either the ACS or CCS phases. These findings challenge their routine use in this population and support reconsidering current guidelines. Long-term beta-blocker users after MI may be candidates for deprescription.