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Extended follow-up of patients in the LIPSIA CONDITIONING trial finds significant clinical benefit in patients who received remote conditioning in combination with ischaemic postconditioning

Paper commented by the ESC WG on Cellular Biology of the Heart



In patients with ST-elevation myocardial infarction (STEMI), prompt reperfusion via primary percutaneous coronary intervention (PCI) is recommended. Despite this, reperfusion can contribute to further myocardial injury. Animal studies demonstrate that ischaemic conditioning applied either directly to the heart following reperfusion (postconditioning) or to an organ remote from the heart (remote ischaemic conditioning) substantially reduces final infarct size.(1) Various clinical studies of the benefit of conditioning strategies in STEMI patients undergoing PCI have been performed, and meta-analyses suggest that they may provide benefit, at least when surrogate markers are examined.(2) However, the crucial question is whether it is possible to demonstrate long-term benefit in patient health and well-being. In this regard, a recent trial of postconditioning in 1,234 patients undergoing PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure.(3) On the other hand, it is possible that in patients, for various reasons(1), a single protective approach may be insufficient, and multi-target strategies may be required to result in clinically meaningful cardioprotection.(4)

In 2015, the prospective, controlled, single-centre LIPSIA CONDITIONING study of 696 STEMI patients reported that those who received RIC in combination with postconditioning exhibited significantly greater myocardial salvage (P=0.02), although no differences were seen in the combined clinical endpoint after 6 months follow up (P = 0.44)(5). Now, however, the authors have returned to examine the same patients following a median of 3.6 years after the index event. After this extended follow-up, there was a significant reduction in the rate of major adverse cardiac events (10.2% in RIC + postconditioning vs 16.9% in the control group; odds ratio, 0.56; 95% CI, 0.32-0.97; P=0.04). Interestingly, the difference was driven by a significantly reduced rate of new congestive heart failure, suggesting that longer term follow-up is necessary to observe this benefit. It is important to note that this study did not include a treatment group to examine the effects of RIC alone, and the analysis was conducted post hoc. In this regard, the results of the large, prospective, randomized clinical trial (CONDI-2/ERIC-PPCI; Unique identifier: NCT02342522; n=5400 patients with STEMI; primary end point: cardiac death and hospitalization for heart failure at 12 months) will be highly informative.

References


  1. Hausenloy DJ, Garcia-Dorado D, Bøtker HE, Davidson SM, Downey J, Engel FB, Jennings R, Lecour S, Leor J, Madonna R, Ovize M, Perrino C, Prunier F, Schulz R, Sluijter JPG, Van Laake LW, Vinten-Johansen J, Yellon DM, Ytrehus K, Heusch G, Ferdinandy. Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart. P. Cardiovasc Res. 2017 May 1;113(6):564-585
  2. McLeod SL, Iansavichene A, Cheskes S. Remote Ischemic Perconditioning to Reduce Reperfusion Injury During Acute ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis. J Am Heart Assoc 2017;6
  3. Engstrom T, Kelbaek H, Helqvist S, et al. Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial. JAMA Cardiol 2017;2:490-497
  4. Davidson SM, Ferdinandy P, Andreadou I, Bøtker HE, Heusch G, Ibáñez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ, Garcia-Dorado D; CARDIOPROTECTION COST Action (CA16225). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Jan 8;73(1):89-99.
  5. Eitel I, Stiermaier T, Rommel KP, Fuernau G, Sandri M, Mangner N, Linke A, Erbs S, Lurz P, Boudriot E, Mende M, Desch S, Schuler G, Thiele H. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. Eur Heart J. 2015 Nov 21;36(44):3049-57
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.