European Heart Journal - Cardiovascular Pharmacotherapy最新文献

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.

Aims: Takotsubo syndrome (TTS) is an acute cardiac condition marked by transient left ventricular dysfunction. Pharmacological management is largely empirical. SGLT2 inhibitors (SGLT2i) offer cardioprotective effects in other cardiovascular diseases, but their impact in TTS is unclear. We thus aim to evaluate whether SGLT2i improves long-term survival after TTS.

Methods and results: We conducted a trial emulation based on real-world data of the TriNetX global network, including patients with TTS diagnosed October 2019-August 2025 (n = 31 018). The primary analysis emulated a de novo pharmacotherapy initiator cohort with a ≤72-h post-diagnosis enrolment window, evaluating the addition of SGLT2i to RAAS inhibitors (RAASi) and beta-blockers (BB). Follow-up began at pharmacotherapy initiation; two-year survival was analysed. Propensity-score matching was performed for age, sex, diabetes, hypertension, dyslipidemia, renal function, initial left ventricular function at diagnosis, and acute severity markers. The median follow-up was 13.3 months. Two-year mortality was 17.5%. After matching (yielding well-balanced 524 patients per group), mortality was significantly reduced in the SGLT2i group compared with RAASi + BB alone (HR 0.56, 95% CI 0.36-0.89). Results were consistent in an extended ≤30-day virtual-enrolment window. A supportive multivariable Cox model considered overall exposure to different therapies (n = 31 018). SGLT2i were associated with the largest reduction in mortality, followed by angiotensin receptor blockers, ACE inhibitors, and BB. Sacubitril/valsartan and MRAs showed no significant association with mortality.

Conclusion: In the largest real-world TTS cohort, SGLT2i were associated with lower long-term mortality. These findings support their consideration in TTS management and justify randomized trials to evaluate SGLT2i as adjunctive therapy.

Aims: 5α-Reductase inhibitors are prescribed for the treatment of benign prostatic hyperplasia (BPH) and their use is associated with increased risk of incident type 2 diabetes. This study assessed the long-term cardiovascular safety of 5α-reductase inhibitors in comparison with tamsulosin in people with co-existing BPH and type 2 diabetes.

Methods and results: We performed a retrospective, population-based cohort study using Scottish Diabetes Research Network National Diabetes Dataset (SDRN-NDS) and IQVIA Medical Research Data (IMRD-UK). BPH patients ≥40 years with recorded type 2 diabetes mellitus and ≥2 prescriptions of 5α-reductase inhibitors or tamsulosin (2006-2021) were included. After 1:2 variable ratio propensity score matching, cause-specific Cox proportional-hazard models were used to compute the hazard ratio (HR) of incident major adverse cardiovascular events (MACE). A total of 11,969 patients were included in SDRN-NDS and 16,492 in IMRD-UK, with median follow-up durations of 3.8 (IQR: 1.7-6.8) and 4.8 (2.0-8.3) years, respectively. In SDRN-NDS, the HR of MACE in patients receiving 5α-reductase inhibitors relative to tamsulosin was 1.15 (95% CI 1.03-1.30, p = 0.007), driven by increased risk for myocardial infarction (MI) (HR 1.20, 1.03-1.40, p = 0.022). This was replicated in IMRD-UK, where HR was 1.26 (1.07-1.47, p = 0.008) for MACE and 1.33 (1.10-1.60, p = 0.005) for MI. We did not observe any increased risks in stroke, cardiovascular death, microvascular complications of diabetes or faster progression to insulin-based therapies.

Conclusions: Our retrospective data from two large cohorts suggest that the risk of MACE may be increased among patients with type 2 diabetes taking 5α-reductase inhibitors, potentially driven by increased risk of MI. This supports careful monitoring of macrovascular outcomes when prescribing 5α-reductase inhibitors in this population.