Letter by Iliodromitis et al Regarding Article, “Cardiac Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: A Prospective, Randomized Control Trial”
To the Editor:
Preconditioning reduces the infarct size in every species. Remote ischemic preconditioning is another effective intervention with promising results1; however, its effectiveness in humans has yet to be proven.
In the Cardiac Ischemic Preconditioning in Coronary Stenting (CRISP Stent) study,2 Hoole et al concluded that remote ischemic preconditioning applied before percutaneous coronary intervention 3 times for 5 minutes each in 1 hand by blood pressure cuff inflation at 200 mm Hg reduced troponin release in a cohort of patients. Another study3 in similar patients found that remote ischemic preconditioning with exactly the same intervention but in both upper limbs a few minutes before percutaneous coronary intervention not only did not reduce but actually slightly increased troponin, creatine kinase, creatine kinase-MB, and C-reactive protein release.
It is of interest that there are significant similarities between the 2 studies in terms of the duration of ischemia, preconditioning protocol, and other methods. There are, however, 2 differences: (1) The timing of the preconditioning protocol in the CRISP Stent study was almost at the point at which the first window of protection fades and any protection is eventually going to be lost, whereas in the other study,3 it was close to the first window of protection by preconditioning; and (2) remote preconditioning was applied in 1 upper arm in the CRISP Stent study but in both upper arms in the second study,3 which might be important in terms of inflammation “load/provocation.”
Alternative interpretations of the results of the CRISP Stent study are possible. The results show that biochemical (troponin) infarction rates were not different between groups. In other words, under this protocol, although a reasonable degree of injury was caused by the percutaneous coronary intervention, this was not reduced by the preconditioning. Only biologically unimportant (noninfarct) troponin level elevation was reduced in the preconditioning group. Because preconditioning postpones ischemic damage, and there is no indication that the test injury was too severe, the only safe conclusion that can be drawn is that small enzyme rises are reduced by remote preconditioning. Although other surrogate end points are of interest, that is what they remain.
Lastly, a mention of the possible role of inflammation is worthwhile. Iliodromitis et al3 found that hypercholesterolemic patients who were not taking statins had the worst outcomes after the intervention, and inflammation appeared to play a critical role. As noted, this may be related to the use of both arms in the preconditioning protocol.3
It remains important to find ways to exploit the powerful protection of preconditioning in the setting of angioplasty. The remote route warrants further investigation; it appears that “too much” might produce an excessive inflammatory response as a side effect, and the timing needs to be worked out.
Przyklenk K, Bauer B, Kloner RA, Whittaker P. Regional ischemic preconditioning protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1992; 87: 893–899.
Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O'Sullivan M, Dutka DP. Cardiac Ischemic Preconditioning in Coronary Stenting (CRISP Stent) study: a prospective, randomized control trial. Circulation. 2009; 119: 820–827.
Iliodromitis EK, Kyrzopoulos S, Paraskevaidis IA, Kolocassides KG, Adamopoulos S, Karavolias G, Kremastinos DT. Increased C reactive protein and cardiac enzyme levels after coronary stent implantation: is there protection by remote ischaemic preconditioning? Heart. 2006; 92: 1821–1826.