Interaction of ischaemic postconditioning and thrombectomy in patients with ST-elevation myocardial infarction.

OBJECTIVE: The Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction - Ischaemic Postconditioning (DANAMI-3-iPOST) did not show improved clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with ischaemic postconditioning. However, the use of thrombectomy was frequent and thrombectomy may in itself diminish the effect of ischaemic postconditioning. We evaluated the effect of ischaemic postconditioning in patients included in DANAMI-3-iPOST stratified by the use of thrombectomy. METHODS: Patients with STEMI were randomised to conventional primary percutaneous coronary intervention (PCI) or ischaemic postconditioning plus primary PCI. The primary endpoint was a combination of all-cause mortality and hospitalisation for heart failure. RESULTS: From March 2011 until February 2014, 1234 patients were included with a median follow-up period of 35 (interquartile range 28 to 42) months. There was a significant interaction between ischaemic postconditioning and thrombectomy on the primary endpoint (p=0.004). In patients not treated with thrombectomy (n=520), the primary endpoint occurred in 33 patients (10%) who underwent ischaemic postconditioning (n=326) and in 35 patients (18%) who underwent conventional treatment (n=194) (adjusted hazard ratio (HR) 0.55 (95%confidence interval (CI) 0.34 to 0.89), p=0.016). In patients treated with thrombectomy (n=714), there was no significant difference between patients treated with ischaemic postconditioning (n=291) and conventional PCI (n=423) on the primary endpoint (adjusted HR 1.18 (95% CI 0.62 to 2.28), p=0.62). CONCLUSIONS: In this post-hoc study of DANAMI-3-iPOST, ischaemic postconditioning, in addition to primary PCI, was associated with reduced risk of all-cause mortality and hospitalisation for heart failure in patients with STEMI not treated with thrombectomy. TRIAL REGISTRATION NUMBER: NCT01435408.

Ischemic postconditioning during primary percutaneous coronary intervention.

BACKGROUND: Although some studies have shown potential benefit for ischemic postconditioning (IPoC) during primary percutaneous coronary intervention (PCI) in improving surrogate markers of reperfusion and infarction size, the benefit of this approach on clinical outcomes remains unknown. METHODS AND RESULTS: Electronic databases were searched for randomized clinical trials that compared IPoC versus conventional treatment during primary PCI. Random effects DerSimonian-Laird risk ratios (RR) were calculated for different clinical and surrogate outcomes. The main outcome of this analysis was all-cause mortality. A total of 25 trials involving 3,619 patients were included in the analysis. At a mean follow up of 14 months (95% confidence interval (CI) 8.6-19.4 months), the incidence of all-cause mortality was 4.9% [95% CI 3.8-6.0%] in the IPoC group versus 3.8% [95% CI 1.9-5.7%] in the control group (RR 0.92, 95% CI 0.68-1.24, P = 0.74). The risk of reinfarction (2.7% [95% CI 1.1-4.3%] vs. 2.3% [0.6-4.0%]; RR 1.29, 95% CI 0.62-2.68, P = 0.72), heart failure (3.6% [95% CI 2.0-5.1%] vs. 5.7% [95% CI 3.3-8.2%]; RR 0.77, 95% CI 0.58-1.06, P = 0.24), target vessel revascularization (3.2% [95% CI 1.7-4.7%] vs. 2.4% [95% CI 1.4-3.3%]; RR 1.40, 95% CI 0.90-2.20, P = 0.20), and stent thrombosis (2.4% [95% CI 1.1-3.8%] vs. 1.8% [95% CI 0.5-3.2%]); RR 1.50, 95% CI 0.60-3.70, P = 0.40) was similar in both groups. CONCLUSIONS: IPoC does not appear to reduce the risk of clinical adverse events in patients with ST-elevation myocardial infarction undergoing primary PCI. © 2017 Wiley Periodicals, Inc.

Ischemic Postconditioning of the Liver Graft in Adult Liver Transplantation.

BACKGROUND: Ischemia-reperfusion (I/R) injury is the main cause of graft failure in liver transplantation (LT). Ischemic postconditioning (IPo) has shown to be beneficial against I/R injury. Our objective was to compare the results of LT with or without IPo. METHODS: One hundred patients undergoing LT alternatively received IPo or not. At the time of arterial reperfusion, IPo consisted of three 1-minute arterial occlusions, interspersed with 1-minute reperfusion pauses. The primary endpoint was postoperative aspartate aminotransferase (AST) peak value; early graft dysfunction and histological I/R injury were secondary endpoints. RESULTS: Median postoperative AST peak values was similar in both groups (426 vs 463 IU/L, P = 0.21); no difference was found in other postoperative liver function tests. In the IPo group, fewer grafts presented severe histological I/R injury (12% vs 28%; P = 0.029). Ischemic postconditioning did not induce changes in cellular apoptosis but triggered autophagy in periportal areas. Independent predictors of severe I/R injury were IPo (odds ratio, 0.20; P = 0.008) and arterial warm ischemia duration (odds ratio, 1.05; P = 0.008). Early graft dysfunction rate was similar in both groups (20% versus 26%, P = 0.47) and was associated with severe histological I/R injury and longer cold ischemia. Morbidity, mortality, and 1-year graft and patient survival were similar in both groups. CONCLUSIONS: Ischemic postconditioning did not influence postoperative AST peak values or other liver function tests. However, our results showed a better tolerance to I/R injury on histological findings of grafts receiving IPo. Future studies are necessary to optimize the IPo protocol in LT, to clarify its clinical impact, and to deepen the molecular understanding.

Surrogate and clinical outcomes following ischemic postconditioning during primary percutaneous coronary intervention of ST--segment elevation myocardial infarction: a meta-analysis of 15 randomized trials.

OBJECTIVES: To conduct a meta-analysis on surrogate and clinical outcomes with myocardial ischemic postconditioning (IPoC) following revascularization with primary percutaneous intervention (PPCI) for ST-segment myocardial infarction (STEMI) compared with PPCI alone. BACKGROUND: Reperfusion injury remains an important problem following PPCI for STEMI. Trials of IPoC have mainly focused on cardiac biomarkers; the impact on clinical outcomes is unknown. METHODS: Clinical trials that randomized STEMI patients to IPoC as compared with conventional PPCI were included for analysis. RESULTS: A total of 15 randomized trials with 1,545 patients met our selection criteria (785 underwent IPoC + PPCI, 760 PPCI alone). Mean follow-up for clinical outcomes was 4.7 months. The mean ischemic time was 225 min. ST-segment resolution (Relative Risk [RR] = 0.98; 95% Confidence Intervals [CI] 0.85-1.13; P = 0.75) and infarct size (Weighted mean difference [WMD] = -2.53%, 95% CI -6.10 to 1.05; P = 0.17) were similar between the IPoC + PPCI vs. PPCI arms. Left ventricular ejection fraction at follow-up was marginally higher in the IPoC (WMD = 4.15%, 95% CI 0.19-8.12%, P = 0.04). No differences were noted in any of the clinical outcomes studied, including mortality (RR = 1.52; 95% CI 0.77-2.99; P = 0.23), recurrent MI (RR = 3.04; 95% CI 0.74-12.54; P = 0.12); stent thrombosis (RR = 1.24, 95% CI 0.51-3.04; P = 0.83) or the composite MACE outcome (RR = 1.53; 95% CI 0.89-2.63; P = 0.13). CONCLUSIONS: IPoC following PPCI is not associated with improvements in surrogate or clinical outcomes at 5 months as compared with PPCI alone. Our findings indicate no role for IPoC in the routine management of patients with STEMI.

Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction (POST) randomized trial.

BACKGROUND: Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment-elevation myocardial infarction. However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. METHODS AND RESULTS: We performed a multicenter, prospective, randomized, open-label, blinded end-point trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction within 12 hours after symptom onset were randomly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: The angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure (<6 atm) inflations, each separated by 1 minute of deflation. The primary end point was complete ST-segment resolution (percentage resolution of ST-segment elevation >70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, -1.0%; 95% confidence interval, -8.4 to 6.4; P=0.79). The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4% [P=0.20] and 4.3% versus 3.7% [P=0.70], respectively). CONCLUSION: Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment-elevation myocardial infarction undergoing primary PCI with current standard practice.

Remote ischaemic postconditioning: does it protect against ischaemic damage in percutaneous coronary revascularisation? Randomised placebo-controlled clinical trial.

OBJECTIVE: Determine whether remote ischaemic postconditioning (RIP) protects against percutaneous coronary intervention-related myocardial infarction (PCI-MI). DESIGN: Single-centre, randomised, blinded to the researchers, clinical trial. ClinicalTrials.gov (NCT 01113008). SETTING: Tertiary hospital centre. PATIENTS: 232 patients underwent elective PCI for stable or unstable angina. INTERVENTIONS: Patients were randomised to RIP (induction of three 5-min cycles of ischaemia in the arm after the PCI) versus placebo. MAIN OUTCOME MEASURES: The primary outcome measure was the peak 24-h troponin I level. PCI-MI was defined by an elevation of troponin values >3 or >5 of the 99th percentile according to the classical or the new definition. The secondary outcome measure was hospital admission, PCI for stable angina or acute coronary syndrome and mortality after 1 year of follow-up. The use of RIP in diabetic patients was specifically studied. RESULTS: The mean age was 64.6 years, and 42% were diabetic. The peak troponin in the RIP patients was 0.476 vs 0.478 ng/mL (p=0.99). PCI-MI occurred in 36% of the RIP patients versus 30.8% in the placebo group (p=0.378). Diabetic RIP patients had more PCI-MI (new definition): OR 2.7; 95% CI 1.10 to 6.92; p=0.027. The secondary outcome measure was seen in 11.7% of the RIP patients versus 10.8% in the placebo group (p=0.907). CONCLUSIONS: RIP did not reduce the damage associated with elective PCI or cardiovascular events during the follow-up. The diabetic population who underwent RIP had more PCI-MI.