META-ANALYSIS ASSESSING THE IMPACT OF PRIOR HEART FAILURE AND CHRONIC KIDNEY DISEASE ON THE CARDIOVASCULAR EFFICACY OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS

Abstract

Objective: Chronic kidney disease (CKD) and heart failure (HF) represent common co-morbidities in patients with type 2 diabetes mellitus (T2DM), constituting an additional burden that boosts overall morbidity and mortality. Therefore, we sought to determine whether history of HF or CKD affects the cardiovascular efficacy of GLP-1RAs, also utilizing data from the recently published FREEDOM Cardiovascular Outcomes Trial, which evaluated the cardiovascular safety of delivering a continuous subcutaneous infusion of the GLP-1RA exenatide (ITCA 650) in T2DM. Design and method: We searched the relevant, hallmark, cardiovascular outcome trials of GLP-1RAs in T2DM. We set as primary efficacy outcome the effect of GLP-1RAs versus placebo on the risk for a major adverse cardiovascular event (MACE) according to the prior history of HF, while we also assessed as a secondary efficacy outcome the effect of GLP-1RAs on the risk for MACE according to a prior diagnosis of CKD. Results: We finally pooled data from 4 trials for a total of 26,272 enrolled participants with T2DM. Regarding the primary efficacy outcome, we demonstrated that GLP-1RAs versus placebo resulted in a significant decrease by 14% (RR = 0.86, 95% CI; 0.76 – 0.97, I2 = 50%), regardless of history of HF (p-value for subgroup differences = 0.88). Concerning the secondary efficacy outcome, we showed that GLP-1RA treatment was superior to placebo in reducing the risk for a MACE (RR = 0.87, 95% CI; 0.75 – 1.02, I2 = 70%), while prior status of CKD did not affect the generated results (p-value for subgroup differences = 1.00). Conclusions: GLP-1RAs seem to constitute a safe and efficacious treatment option in patients with T2DM and established or at high risk for atherosclerotic cardiovascular disease, while HF or CKD status at baseline do not substantially affect the observed cardio-protective effect against hard cardiovascular endpoints.