Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial

Abstract

Importance: Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage.

Objective: To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Design, setting, and participants: In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat.

Interventions: Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation.

Main outcome and measures: A combination of all-cause death and hospitalization for heart failure.

Results: During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure.

Conclusions and relevance: Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival.

Trial registration: clinicaltrials.gov Identifier: NCT01435408.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Engstrøm reports receiving fees from Boston Scientific, St Jude Medical, AstraZeneca, and Bayer. Dr Clemmensen reports fees/grants from Medtronic, Eli Lilly, Daiichi-Sankyo, AstraZeneca, Bayer, Boehringer-Ingelheim, Sanofi, Pfizer, and BMS. Dr L.O. Jensen reports fees/grants from St Jude Medical, Biotronic, and Biosensors. Dr Pedersen reports fees/grants from Novo, Biotronic, Bristol-Myers Squibb, Sanofi, and Bayer. Dr Køber reports receving fees from Servier. No other disclosures were reported.

Figures

Figure 1.. CONSORT Study Flow Diagram

Randomization of patients in the Third Danish Study of Optimal Acute Treatment of Patients With ST Elevation Myocardial Infarction–Ischemic Postconditioning (DANAMI-3–iPOST). CABG indicates coronary artery bypass grafting; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; and TIMI, thrombolysis in myocardial infarction. aTwenty patients had 2 exclusion criteria. bGrades range from 0 to 3, with 3 indicating higher flow.

Figure 2.. Kaplan-Meier Curves of the Primary End Point

A, Event rates of the combined primary outcome (all-cause mortality [B] and hospitalization for heart failure [C]) in the Third Danish Study of Optimal Acute Treatment of Patients With ST Elevation Myocardial Infarction–Ischemic Postconditioning (DANAMI-3–iPOST) are shown from the time of the primary percutaneous intervention to 40 months after the index treatment. The Cox proportional hazards model was used to calculate hazard ratios (HRs), 95% CIs, and P values.