European Heart Journal - Cardiovascular Pharmacotherapy最新文献

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.

Background: Left ventricular (LV) thrombus is a severe complication of acute myocardial infarction (AMI) and chronic heart failure. While current guidelines support the use of direct oral anticoagulants (DOAC) as alternatives to vitamin K antagonists (VKA), their benefit across different aetiologies remains uncertain. This study aimed to compare the efficacy and safety of DOAC versus VKA across different aetiologies of LV dysfunction.

Methods: We conducted a multi-centre observational study including 901 patients with confirmed LV thrombus treated with either a VKA or DOAC. The primary outcome was thrombus resolution, secondary outcomes included stroke and systemic embolisation (SSE), major bleeding and mortality with analyses performed by aetiology.

Results: The principal aetiologies were AMI (38.3%), ischaemic cardiomyopathy (ICM) (38.0%) and non-ischaemic cardiomyopathy (NICM) (23.7%). Overall, thrombus resolution was significantly higher in DOAC treated patients, but this was driven by the AMI sub-group (p=0.018). DOAC use independently predicted thrombus resolution (OR 2.0, 95% Cl 1.29-3.24, p=0.010). Major bleeding events (BARC ≥3) were more common with VKA use (p=0.008). NICM had the highest SSE rate (15.3%, p=0.002), which were significantly raised in those treated with DOAC (p<0.001).

Conclusions: The underlying aetiology of LV dysfunction significantly influences both treatment response and outcomes in patients with LV thrombus. DOAC were associated with superior efficacy and safety in AMI-related LV thrombus, but were linked to increased rates of SSE in NICM. These findings highlight the importance of aetiology on LV thrombus management and the potential need for tailored approaches.

Aims: To assess whether rivaroxaban is associated with a decreased risk of major adverse limb events (MALE), stroke, systemic embolism (SE), and major bleeding (MB) among patients with non-valvular atrial fibrillation (NVAF) and peripheral artery disease (PAD), compared with apixaban.

Methods and results: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink. Patients aged ≥45 years with incident NVAF and PAD who initiated rivaroxaban or apixaban between 2013 and 2021 were included. Primary effectiveness outcomes were MALE, and a composite of ischaemic stroke, transient ischaemic attack (TIA), or SE. The primary safety outcome was MB. The risk of major cardiovascular events (MACE) was assessed as a secondary outcome. Confounding was addressed using propensity score fine stratification and weighting. Weighted Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). The cohort included 6170 new users of rivaroxaban and 9990 new users of apixaban (44% female; mean [SD] age 78.5 [9.2] years). Incidence rates were similar for MALE (6.7 vs. 5.6/1000 person-years; adjusted HR (aHR): 1.20; 95% CI 0.87-1.65), stroke/TIA/SE (24.5 vs. 21.3/1000 person-years; aHR: 1.15; 95% CI 0.97-1.36), and MACE (40.1 vs. 35.9 per 1000 person-years; aHR 1.10: 95% CI 0.94-1.28). Major bleeding rates were higher with rivaroxaban (46.1 vs. 29.8/1000 person-years; aHR: 1.55; 95% CI 1.36-1.77).

Conclusion: In patients with NVAF and PAD, rivaroxaban was associated with a similar risk of MALE and stroke/TIA/SE, but a higher risk of MB compared with apixaban. These findings support apixaban as a potentially safer anticoagulant in this high-risk population.

Post-operative atrial fibrillation (POAF) is common after non-cardiac surgery. Because often transient, there are uncertainties on the associated risk of stroke, possibly driving the need for long-term anticoagulation. We performed a systematic PubMed search until 16 January 2025, related to the incidence of stroke in patients with POAF after non-cardiac surgery. We included papers reporting outcomes, excluding studies only dealing with epidemiology, mechanisms, management, and treatment. We excluded studies reporting on POAF after cardiac surgery. Risk of bias was assessed for each study, and the certainty of evidence was evaluated using the GRADE methodology. We retrieved and included 40 studies (including review papers) for the systematic review. These were then further selected to create a final list of 19 studies included in the meta-analysis. The reported incidence of stroke after POAF was found to be widely variable, ranging between 0.4% and 16.7% at 1 year. Stroke incidence also varies widely according to the type of surgery and patient characteristics. With only three exceptions, all studies, however, reported a risk of stroke higher in the POAF group than in the no-POAF group, with a mean odds ratio of 3.02. POAF on average triples the risk of stroke, with variations related to patient characteristics and type of surgery. Patients after non-cardiac surgery should be monitored at least during hospitalisation to detect POAF. Future studies are necessary to evaluate optimal duration and modalities of monitoring, as well as to assess the relevance of symptomatic vs asymptomatic AF episodes.