Comparative Cardiovascular Research Articles

790-P: An Indirect Treatment Comparison of the Cardiovascular Protective Effect of Semaglutide vs. Liraglutide in Subjects with Type 2 Diabetes

Background: In the absence of head-to-head evidence, an indirect treatment comparison (ITC) using individual-level participant data was conducted to provide evidence of the comparative cardiovascular (CV) protective effect of liraglutide vs semaglutide in subjects with type 2 diabetes. Methods: CV outcomes trials (CVOTs) were identified for comparators of interest. LEADER was a randomised controlled trial studying the CV protective effect of liraglutide vs placebo. Similarly, two CVOTs comparing semaglutide with placebo were identified: SUSTAIN 6 and PIONEER 6. Time to first 3-point major adverse CV events (3P-MACE) (adjudicated) was the primary outcome in all trials and was chosen as the primary outcome for the ITC. Potential effect modifiers (baseline indicators of prior CV disease, albumin:creatinine ratio, estimated glomerular filtration rate) were identified in the literature and adjusted for in the ITC. A fixed-effects ITC using individual participant data was conducted in a Bayesian setting. Missing data for potential effect modifiers were imputed using multiple imputation (20 imputations). Comparisons were summarised as cause-specific hazard ratios (HRs). Population-average relative treatment effects between liraglutide and semaglutide were reported for each of the three populations corresponding to the three studies. Results: The ITC showed that the relative risk of semaglutide vs liraglutide for the occurrence of 3P-MACE in the LEADER population favoured semaglutide: HR 0.73 (95% credible interval [CrI]: 0.56;0.94); results also favoured semaglutide in the SUSTAIN 6 (HR 0.76 [95% CrI: 0.59;0.97]) and PIONEER 6 (HR 0.78 [95% CrI: 0.60;1.00]) populations. Conclusion: The results demonstrated a risk reduction of CV events (3P-MACE) for semaglutide vs liraglutide of 22-27% depending on the population studied. These results may have implications for clinical practice. Disclosure B.Chubb: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. M.Bøg: Employee; Lundbeck, Novo Nordisk.

Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat

BackgroundTo re-evaluate comparative cardiovascular (CV) safety of febuxostat versus allopurinol among patients with gout following recent accumulated use of febuxostat. MethodsUsing 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, 1:1 matched on a propensity-score (PS) for >60 covariates. The primary outcome was a composite endpoint of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were individual components of the primary outcome, hospitalized heart failure, and all-cause mortality. Subgroup analyses were done for those at high CV risk, long-term users (follow-up >3 years), and those without chronic kidney disease. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsWe included 160,930 PS-matched pairs of febuxostat and allopurinol users (mean age 59.3 years, 79.6% male). Incidence rates of the primary outcome were 2.06 and 2.27 per 100 person-years for febuxostat and allopurinol users, respectively, with a HR [95% CI] of 1.03 [0.95-1.12] comparing febuxostat versus allopurinol initiators. We also observed similar risks for secondary outcomes, except for reduced all-cause mortality among febuxostat users (HR [95% CI] of 0.84 [0.78-0.91]). Subgroup analyses also showed non-inferior CV safety of febuxostat. ConclusionIn this population-based cohort study including the largest number of febuxostat users to date, we found non-inferior CV safety of febuxostat versus allopurinol. There was a 16% reduction in all-cause mortality among febuxostat users.

133-LB: Cardiovascular Outcomes in Older Adults Initiating Empagliflozin vs. DPP-4 Inhibitors and GLP-1 Receptor Agonists: A Subgroup Analysis from the EMPRISE Study

EMPRISE aims to study the effectiveness, safety and healthcare utilization of empagliflozin (EMPA) in routine care patients. In an interim analysis, we assessed the comparative cardiovascular (CV) effectiveness of EMPA in older adults. Using data from Medicare (2014-2017), we identified 11,579 pairs of 1:1 propensity score-matched patients ≥66 years with type 2 diabetes initiating EMPA or a DPP-4 inhibitor (DPP-4i), and 17,500 pairs initiating EMPA or a GLP-1 receptor agonist (GLP-1RA). We assessed hospitalization for heart failure (HHF), defined as a HF discharge diagnosis in the primary (HHF-Specific) or in any position (HHF-Broad) and a modified MACE outcome (MI, stroke, or all-cause mortality). We estimated HR and 95% CI adjusting for >140 baseline covariates. Compared to DPP-4i, EMPA was associated with a decreased risk of HHF [HHF-Specific: 0.43 (0.30-0.63); HHF-Broad: 0.57 (0.47-0.69)] and MACE [HR (95% CI) = 0.63 (0.50-0.79)]. Compared to GLP-1RA, EMPA had a reduced risk of HHF [HHF-Specific: 0.67 (0.50-0.91); HHF-Broad: 0.83 (0.71-0.96)] and a similar risk of MACE [1.02 (0.85-1.23)](Table 1). Results for the individual components of MACE were consistent and robust to competing risks. These findings, addressing the comparative effectiveness of EMPA in routine care patients with mean age of 72 years, complement available information from RCTs. Disclosure E. Patorno: Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Pawar: None. L.G. Bessette: None. M. Najafzadeh: None. D.J. Wexler: Other Relationship; Self; Novo Nordisk A/S. J. Franklin: None. A. Deruaz-Luyet: Employee; Self; Boehringer Ingelheim International GmbH. Employee; Spouse/Partner; Sanofi-Aventis Deutschland GmbH. K. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. L. Koeneman: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. S. Schneeweiss: None. Funding Boehringer Ingelheim