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Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI).

Bruno García Del BlancoImanol OtaeguiJosé F Rodríguez-PalomaresAntoni Bayés-GenisEduard Fernández-NofreríasVictoria Vilalta Del OlmoXavier CarrilloBorja IbáñezFernando WornerJuan CasanovaEva PueoJose R González-JuanateyJavier López-PaisAlfredo BardajíGil BonetMónica FuertesAntonio Rodriguez-SinovasMarisol Ruiz-MeanaJavier InserteIgnasi BarbaSandra Gómez-TalaveraGerard MartíBernat SerraNeus BelleraManuel Ojeda-RamosHug CuellarFilipa ValenteMaria Ángeles CarmonaElisabet Miró-CasasJosep R MarsalAntonia SambolaRosa M LidónJordi BañerasJaime ElízagaFerran PadillaJosé A BarrabésDerek J HausenloyIgnacio Ferreira-GonzálezDavid García-Dorado
Published in: Basic research in cardiology (2021)
Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.
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