European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: This study, using a prospective cohort, evaluated the effectiveness and safety of off-label reduced-dose apixaban vs. the on-label dose in atrial fibrillation (AF) patients meeting a single-dose reduction criterion.

Methods and results: The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicentre, prospective observational cohort involving AF patients who met a single-dose reduction criterion of apixaban. Patients were divided into two groups: an on-label standard dose (5 mg twice daily) and an off-label reduced dose (2.5 mg twice daily). The primary effectiveness outcome was stroke/systemic embolism (SSE), and the primary safety outcome was major bleeding. Of 1944 patients (mean age 74.3 ± 7.9 years, 56% women), 997 (51%) were receiving off-label reduced-dose apixaban. The off-label reduced-dose group was older, had more comorbidities, higher concomitant antiplatelet use, and higher CHA2DS2-VASc and HAS-BLED scores. During follow-up (1.0 ± 0.2 year), crude incidence rates were 0.9 vs. 0.7 per 100 person-years for SSE and 0.5 vs. 1.0 for major bleeding in the on-label vs. off-label groups. After inverse probability of treatment weighting, the off-label reduced-dose group showed no significant differences in the risk of SSE [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.28-1.59, P = 0.370] and major bleeding (HR 1.38, 95% CI 0.44-4.35, P = 0.578) compared with the on-label standard dose group.

Conclusion: In Korean patients with AF meeting a single-dose reduction criterion of apixaban, off-label reduced-dose apixaban showed no significant differences in SSE and major bleeding compared with the on-label standard dose. These findings suggest that individualized anticoagulation strategies, such as reduced-dose apixaban, may be beneficial for patients with a high risk of bleeding.

Aims: Therapeutic advancements have significantly enhanced cancer patient survival rates yet concomitantly increased the prevalence of associated toxicities, such as cancer therapy-related cardiac dysfunction (CTRCD), either symptomatic (heart failure) or not. Using the World Health Organization's VigiBase® individual case safety report database, the aim was to establish the association between anticancer drugs and CTRCD reporting.

Methods and results: This study was a disproportionality analysis conducted in VigiBase® from the initial report of any anticancer drug until 29 February 2024. Reporting odds ratios for CTRCD were evaluated using a stepwise selection procedure and multivariable-adjusted analyses. Subsequently, secondary analyses consisted of the description of CTRCD cases associated with the identified anticancer drugs. ClinicalTrials.gov registration number: NCT06268535. Among 36 580 288 database reports, 42 828 CTRCD cases associated with at least one anticancer drug were identified with death reported in 20.6% of cases (8833 CTRCD cases). Primary analysis revealed 25 anticancer drugs significantly associated with CTRCD reporting, with trastuzumab, doxorubicin, and bortezomib exhibiting the strongest associations. Cancer therapy-related cardiac dysfunction reporting was associated with kinase inhibitors, including BCR-ABL inhibitors, ibrutinib, and osimertinib. New signals were identified for trabectedin, clofarabine, fludarabine, entrectinib, gemtuzumab ozogamicin, and anagrelide. In contrast, immune checkpoint inhibitors and most anti-vascular endothelial growth factor therapies showed no association with CTRCD.

Conclusion: This disproportionality study identified 25 anticancer drugs significantly associated with CTRCD reporting, including new signals. It highlights discrepancies compared with drugs recommended for cardiac dysfunction evaluation in the 2022 ESC Guidelines. This underscores the importance of including CTRCD as a safety endpoint in cancer studies.

Aims: Cardiovascular disease and cancer represent significant global health challenges. An overlap between oncology and cardiology is compounded by cancer therapies, which are known to have cardiotoxic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for treating diabetes, have shown promising cardiovascular benefits in non-cancer populations, particularly in preventing heart failure (HF) and reducing HF-related hospitalization and mortality in large randomized controlled trials (RCTs) across the spectrum of left ventricular ejection fraction. However, their potential cardioprotective role in cancer patients remains unclear. This systematic review and meta-analysis evaluated cardiovascular outcomes in cancer patients with type 2 diabetes undergoing chemotherapy with concomitant use of SGLT2i compared with those not using SGLT2i. Subgroup analyses were performed to explore patients without baseline HF and patients treated exclusively with anthracyclines.

Methods and results: A systematic review identified 11 observational retrospective studies (n = 104 327 patients). Based on the National Institutes of Health Quality Assessment Tool checklist, two studies were at moderate risk of bias, while all other included studies had a low risk of bias. Meta-analysis indicated that the use of SGLT2i was associated with a significant reduction in all-cause mortality [0.47, 95% confidence interval (CI) 0.33-0.67, P < 0.0001] and risk of HF hospitalization (0.44, 95% CI 0.27-0.72, P = 0.001).

Conclusion: The use of SGLT2i may be associated with a significant reduction in all-cause mortality and risk of HF hospitalization in actively treated cancer patients with Type 2 diabetes. Our study highlights the need for further investigation through prospective RCTs to confirm the efficacy and safety of SGLT2i in attenuating cardiotoxicity and supporting cardiovascular health in oncology settings.

Aims: Managing patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) is challenging. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) show cardiovascular benefits, the impact of combining these agents is unclear. This study evaluated whether adding GLP-1 RA to SGLT2i provides additional benefits in patients with both ASCVD and HF.

Methods and results: This retrospective observational study utilized the TriNetX database to analyse patients with ASCVD and HF who initiated GLP-1 RA with SGLT2i or SGLT2i alone from 1 August 2016 to 30 September 2024. A total of 2 797 317 patients were identified, with 96 051 patients meeting inclusion criteria. After propensity score matching, 5272 patients in each group were analysed. Primary outcomes included mortality or hospitalization within 1 year; secondary outcomes examined mortality, hospitalization, and heart failure exacerbation (HFE). Patients receiving GLP-1RA and SGLT2i therapies had significantly lower risk of mortality or hospitalization [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.74-0.83], mortality (HR 0.72; 95% CI 0.62-0.84), hospitalization (HR 0.78; 95% CI 0.73-0.83), and HFE (HR 0.77; 95% CI 0.72-0.83) vs. SGLT2i alone. Subgroup analyses showed consistent benefits in patients with HFpEF, HFrEF, patients with diabetes, obesity, chronic kidney disease, or those using semaglutide or dulaglutide, while liraglutide use showed a neutral effect. Drug-related side effects were monitored as safety outcomes, which showed no significant differences between groups.

Conclusions: In ASCVD and HF patients, adding GLP-1 RA to SGLT2i reduces 1-year mortality and hospitalization, warranting further investigation in diverse settings.

Type 1 diabetes is associated with excess cardiovascular risk. In contrast to type 2 diabetes, however, age at the onset of type 1 diabetes and sex are major predictors of cardiovascular risk, while the role of low-density lipoprotein cholesterol (LDL-C) and lipid-lowering therapy is less clear. Since most data on the effects of lipid-lowering treatments are obtained from randomized clinical trials that included very predominantly patients with type 2 diabetes, it is almost impossible to specifically discern endpoints in type 1 diabetes. Inversely, most data specific for type 1 diabetes are obtained from real world findings. Consequently, the evidence on efficacy and safety of lipid-lowering therapies available from randomized clinical trials arises very predominantly from type 2 diabetes. Thus, this specific review summarizes the evidence of lipid-lowering drug classes in reducing cardiovascular risk in patients with type 1 diabetes.

LDL cholesterol (LDL - c) and non-HDL cholesterol (non-HDL-c) are prognostic factors of cardiovascular risk. However, their validity as trial-level surrogates for cardiovascular outcomes is debated. This study aimed to determine whether LDL - c and non-HDL-c are reliable surrogates for cardiovascular events in statin trials, and to explore discrepancies in previous studies. We conducted an umbrella review of meta-analyses of randomized controlled trials (RCTs) assessing statin efficacy versus placebo or usual care on all-cause mortality and cardiovascular events. We search studies published between 1987 and August 2023 from PubMed, Embase, and the Cochrane Library. Baseline lipid levels, absolute risk differences (ARDs), and hazard ratios or risk ratios (RRs) for major cardiovascular events and all-cause or cardiovascular mortality were analysed. Weighted linear regressions between log RR or ARD, and absolute difference in non-HDL-c or LDL - c were performed. The coefficients of determination (R2trial) were calculated, with their 95% CI computed through bootstrapping. The surrogate threshold effect (STE) was also estimated. Twenty RCTs and 194 686 participants were included, with a median follow-up of 4.85 years. Statin treatment showed significant efficacy in improving all clinical outcomes. However, the association between treatment effects on LDL - c or non-HDL-c reduction and clinical outcomes was weak. The R²trial were ranging from 0 to 0.1 for LDL - c, and from 0 to 0.04 for non-HDL-c. The STE for major adverse cardiovascular event was 0.76 (0.36-1.69) mmol/L for LDL - c, and 0.87 (0.49-2.19) mmol/L for non-HDL-c. Neither LDL - c nor non-HDL-c demonstrated trial-level surrogacy for predicting treatment effects on mortality and cardiovascular events in statin trials. Although they are relevant biomarkers for the follow-up of patients treated with statins, their reduction does not reliably predict a similar reduction in cardiovascular risk. As such, they should not be used as pivotal evidence in drug trials.

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve heart failure (HF) outcomes but their effects on acute myocardial infarction (AMI) remain poorly characterized. This study aimed to evaluate the 1-year cardiovascular outcomes of SGLT2-Is among patients with AMI.

Methods and results: We conducted an observational, retrospective cohort study using TriNetX data, including patients aged ≥18 with AMI identified via ICD-10 codes regardless of left ventricular ejection fraction (LVEF), categorized by SGLT2-Is use. Propensity score matching (PSM) was performed to balance baseline demographics, comorbidities, and medication use. Adjusted odds ratios (aORs) were estimated for the primary outcome (recurrent AMI) and the secondary outcomes (acute HF hospitalizations, stroke, all-cause hospitalizations, all-cause mortality, new-onset atrial fibrillation, and cardiac arrest). After PSM, 89 554 patients were analysed (44 777 SGLT2-Is users; 44 777 non-users). The mean age was ∼68 years in both cohorts with a similarly high burden of cardiovascular comorbidities. Mean follow-up duration was 290.854 days for SGLT2-Is users and 284.465 days for non-users. SGLT2-Is use was linked to lower rates of recurrent AMI [aOR: 0.459; 95% confidence interval (CI): 0.367-0.551], all-cause hospitalizations (aOR: 0.782; 95% CI: 0.762-0.803), all-cause mortality (aOR: 0.640; 95% CI: 0.612-0.670), and cardiac arrest (aOR: 0.834; 95% CI: 0.773-0.900). No differences were observed in acute HF hospitalizations, new-onset atrial fibrillation, or stroke.

Conclusion: SGLT2-Is are associated with improved cardiovascular outcomes in patients with AMI, including reductions in recurrent AMI, all-cause hospitalizations and mortality, and cardiac arrest. These findings emphasize the need for prospective clinical trials involving patients with AMI and other cardiovascular comorbidities, regardless of LVEF, to confirm these results.