Impact of cardiovascular risk factors and medication use on the efficacy of remote ischaemic conditioning: post hoc subgroup analysis of a randomised controlled trial

Abstract

ObjectivesRemote ischaemic conditioning (RIC) promotes cardioprotection in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI). The effect of RIC may be modified by cardiovascular risk factors and their medications. We examined whether cardiovascular risk factors, lipid and glucose levels, and medication use influenced the efficacy of RIC in patients with STEMI treated with pPCI.DesignPost hoc subgroup analysis of a single-centre randomised controlled trial.ParticipantsA total of 139 patients with STEMI, randomised during ambulance transport to hospital for pPCI with (n=71) or without (n=68) RIC, met the trial criteria and achieved data for a myocardial salvage index (MSI).InterventionsRIC was administered through intermittent arm ischaemia with four cycles of 5 min inflation and 5 min deflation of a blood pressure cuff.Primary outcome measuresMSI, estimated by single-photon emission CT. We evaluated the efficacy of RIC on the MSI in patient subgroups of cardiovascular risk factors, lipid and glucose levels, and medication use.ResultsWe found no significant difference in the efficacy of RIC in subgroups of cardiovascular risk factors, lipid and glucose levels, and medication use. However, point estimates indicated a reduced effect of RIC among smokers (median difference in MSI between RIC and control groups: −0.02 (95% CI −0.32 to 0.28) in smokers vs 0.25 (95% CI 0.08 to 0.42) in non-smokers, p value for interaction=0.13) and an increased effect of RIC in statin users (median difference in MSI between RIC and control groups: 0.34 (95% CI 0.03 to 0.65) in statin users vs 0.09 (95% CI −0.11 to 0.29) in non-statin users, p value for interaction=0.19).ConclusionsRIC as an adjunct to pPCI seems to improve MSI in our trial population of patients with STEMI regardless of most cardiovascular risk factors and their medications. Our post hoc finding on a limited sample size calls for further investigation in large-scale multicentre trials.Trial registration numberNCT00435266.

Time to Give Up on Cardioprotection?

“…P P P P P P P P P P P P P P P P P in all age cohorts of patients with acute STEMI undergoing primary PCI. 180 However, patients with coronary artery disease have also been exposed to risk factors and comorbidities that increase the sensitivity to myocardial ischemia/ reperfusion injury and attenuate cardioprotective signaling, such as hypertension, 181,182 hypercholesterolemia, 183,184 and diabetes mellitus. [185][186][187][188][189] Patients with coronary artery disease have endothelial dysfunction.…”

“…73,110,192 However, in a recent retrospective analysis for confounders, risk factors and diabetes mellitus did not interfere with protection by remote ischemic perconditioning in patients with AMI. 180 Apart from and in addition to comorbidities, medications are significant confounders of cardioprotection, either because they induce cardioprotection per se and leave less room for protection by a conditioning intervention or because they interfere with the signal transduction of a conditioning intervention. Statins not only reduce myocardial ischemia/reperfusion injury per se, [193][194][195][196] but may-with chronic use-also interfere with cardioprotective signaling.…”

“…197 However, in a recent retrospective analysis for confounders, statin use even facilitated protection by remote ischemic perconditioning in patients with AMI. 180 Antihypertensive treatment with angiotensin-converting enzyme inhibitors or angiotensin type 1 receptor antagonists may reduce infarct size and improve clinical outcome per se 198,199 (for review see Kleinbongard and Heusch 30 ), and these agents may also facilitate protection by conditioning interventions. 181,200 The same may be true for β-blockade, specifically for metoprolol, 201 but β-blockade may also abrogate the protection by conditioning interventions.…”

Confounders of Cardioprotection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting

“…Diabetes was found to confound protection by RIC in patients undergoing an elective percutaneous coronary intervention (PCI) [2], but not in the retrospective analysis of the CONDI trial of patients undergoing primary PCI [24]. In an extension of our original trial, protection by RIC was not abrogated by diabetes per se, but by treatment with sulphonylureas [25].…”

“…Statins potentially increase [24] and β-blockers attenuate RIC-induced protection [27]. Statins and β-blockers, but also clopidogrel, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) reduce infarct size per se [28], and may thus interfere with RIC-induced protection.…”