European Heart Journal - Cardiovascular Pharmacotherapy最新文献

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.

The clinically important link between LDL cholesterol (LDL - C) lowering and cardiovascular (CV) risk reduction is well-established and reflected in the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemia. They recommend a stepwise approach to reaching LDL - C goals, beginning with statin monotherapy at the highest tolerated dose. However, real-world data show a large gap between guideline LDL - C goal recommendations and their achievement in clinical practice. The treatment paradigm should shift from the concept of high-intensity statins to that of high-intensity, lipid-lowering therapy (LLT), preferably as upfront combination LLT, to overcome the residual CV risk associated with inadequate lipid management. A multidisciplinary expert panel convened to propose treatment algorithms to support this treatment approach in patients at high and very high CV risk. The experts completed a questionnaire on the benefits of combination therapy and the role that novel LLTs, including bempedoic acid, might play in future guidelines. The integration of new LLTs into the suggested treatment algorithms for patients at high CV risk, very high CV risk, and those with complete or partial statin intolerance was discussed. Each algorithm considers baseline CV risk and LDL - C levels when recommending the initial treatment strategy. This expert consensus endorses the use of statin combination therapy as first-line therapy in patients at high and very high CV risk, and, in some circumstances, in patients with statin intolerance when appropriate. Given recent, compelling evidence, including real-world data, combination therapy as first-line treatment should be considered to help patients achieve their LDL - C goals.