Response to Letters Regarding Article, “Cardiac Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: A Prospective, Randomized Control Trial”
In the Cardiac Ischemic Preconditioning in Coronary Stenting (CRISP Stent) study,1 we aimed to assess the potential therapeutic benefit of remote ischemic preconditioning (IPC) applied in a real-world clinical scenario of elective percutaneous coronary intervention. To this end, we had broad patient inclusion criteria and used remote IPC before patients entered the catheterization laboratory. The comments of Iliodromitis et al are of interest, but their speculation on the reason for the differences between their study2 and the CRISP study is not supported by the available data. Although protection wanes with time (greater protection appeared to occur when cuff-to-balloon times were short), a protocol that uses on-table remote IPC is not sustainable in a busy percutaneous coronary intervention center. Furthermore, the therapeutic effect of remote IPC can only be elicited in a setting of ischemia-reperfusion injury. Low-risk patients receiving direct short stents, as in the study by Iliodromitis et al,2 may have little or no microcirculatory injury, and protection from remote IPC would not be expected to be evident, nor would it be required. The incidence of any cardiac troponin I release after percutaneous coronary intervention reflects myocardial infarction associated with percutaneous coronary intervention (MI4a), and we believe that the reduction in troponin release after percutaneous coronary intervention in the CRISP study may be prognostically important and worthy of further investigation. Any intervention that results in less myocyte loss and thereby reduced cardiac troponin I release after elective percutaneous coronary intervention must a priori be beneficial.3,4 Single-arm remote IPC was not proinflammatory, albeit in a statin-treated population. It is reassuring that our study confirms that single-arm remote IPC is a safe therapy.
The comments of Attaran are interesting. We would be surprised if the nonsignificant difference in drug-eluting stent usage between the groups contributed to the difference in major adverse cardiac and cerebral events observed, but it is theoretically possible. Drug-eluting stents and bare-metal stents share the same stent platform design. We have not demonstrated significant differences in cardiac troponin I release between different stent types. Albertal et al raise the issue of the clinical scenario and confounding variables. The use of periprocedural preconditioning-mimetic agents was similar in both groups: opiates (11% versus 10%, P=0.82) and nitrates (72% versus 75%, P=0.75). We accept that in the case of chest pain reporting, there may have been an inevitable placebo effect; however, this would not be expected to impact the primary end point. We agree that the degree of collateralization is an important determinant of area of myocardium at risk, and coronary balloon occlusion time could provide local IPC. However, both groups had similar collateralization and coronary balloon occlusion times. Despite multistenting in 17% of the patients, the total coronary balloon occlusion times in both groups were below the threshold required for IPC to occur.
Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O'Sullivan M, Dutka DP. Cardiac Remote 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.
Bonello L, De Labriolle A, Lemesle G, Steinberg DH, Roy P, Xue Z, Torguson R, Kaneshige K, Suddath WO, Satler LF, Kent KM, Pichard AD, Lindsay J, Waksman R. Prognostic value of procedure-related myocardial infarction according to the universal definition of myocardial infarction in saphenous vein graft interventions. Am Heart J. 2009; 157: 894–898.