Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: Rationale and Study Design for the RIC-AFRICA Trial

Abstract

Purpose Despite evidence of myocardial infarct size reduction in animal studies, remote ischaemic conditioning (RIC) failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. Potential reasons include that the predominantly low-risk study participants all received timely optimal reperfusion therapy by primary percutaneous coronary intervention (PPCI). Whether RIC can improve clinical outcomes in higher-risk STEMI patients in environments with poor access to early reperfusion or PPCI will be investigated in the RIC-AFRICA trial. Methods The RIC-AFRICA study is a sub-Saharan African multi-centre, randomized, double-blind, sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 h or arrive outside the thrombolytic window (12–24 h). Participants will receive either RIC (four 5-min cycles of inflation [20 mmHg above systolic blood pressure] and deflation of an automated blood pressure cuff placed on the upper arm) or sham control (similar protocol but with low-pressure inflation of 20 mmHg and deflation) within 1 h of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 h after chest pain but within 72 h will be recruited to participate in a concurrently running independent observational arm. Conclusion The RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk sub-optimally reperfused STEMI patients, thereby providing a low-cost, non-invasive therapy for improving health outcomes.

Reperfusion Injury: How Can We Reduce It by Pre-, Per-, and Postconditioning

“…Therefore, clinical trials testing the effect of ischemic conditioning in high-risk STEMI populations are needed [ 90 ]. The ongoing RIC-AFRICA trial is going to investigate the effect of RIC in such a high-risk population with a higher prevalence of cardiovascular risk factors, suboptimal use of secondary prevention, and poor access to early reperfusion with pPCI [ 91 ].…”

The Impact of Serial Remote Ischemic Conditioning on Dynamic Cerebral Autoregulation and Brain Injury Related Biomarkers

“…There is now good evidence for RIC as an effective adjunctive treatment in the cardiovascular field although the protection mechanism mediated by the RIC still remains not completely known at the moment ( Ho et al, 2020 ; Guo et al, 2021 ; Lukhna et al, 2021 ). However, for cerebrovascular diseases, there is varying level of evidence.…”

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

“…These studies in high-income countries emphasize the logistical constraints imposed by geography, weather, and socio-economic disparities in healthcare. When these issues are faced in the context of low-income countries like Sub-Saharan Africa, the magnitude of the task and the obstacles to optimal reperfusion therapy are exceptionally challenging, and potentially the role of the cardioprotection is much greater [ 32 ] in that the cardioprotective effects of the pharmacological and non-pharmacological approaches may increase with the duration of ischemia. An example of the dramatic adverse impact of treatment delay on the outcomes of an invasive strategy for STEMI was highlighted by a prospective registry of patients in 55 interventional centers primarily in the United Kingdom and Europe during the initial days of the COVID pandemic [ 33 ].…”

“…In this setting, RIC remains a highly promising, innovative, and biologically plausible strategy which needs to be tested in different clinical settings. Much needed trials and ongoing trials include the RIP-HIGH trial in patients with Killip class 2 or higher in Germany (NCT 04844931) and the RIC-AFRICA trial in South Africa, Sudan, Uganda, and Kenya [ 42 ].…”