RIC Remote Ischemic Conditioning to reduce reperfusion injury during acute STEMI: A systematic review and meta-analysis

Transcription

1 RIC Remote Ischemic Conditioning to reduce reperfusion injury during acute STEMI: A systematic review and meta-analysis [McLeod SL, Iansavitchene A, Cheskes S] Sheldon Cheskes, MD CCFP(EM) FCFP Medical Director, Sunnybrook Centre for Prehospital Medicine Associate Professor, Division of Emergency Medicine, University of Toronto Scientist, Li Ka Shing Knowledge Institute, St. Michael s Hospital Co-Principal Investigator, Toronto RescuNet, Resuscitation Outcomes Consortium Disclosure Financial Disclosure: CIHR/NIH funding Resuscitation Outcomes Consortium Speakers Honorarium CPR Quality (Zoll Medical/ Physio-Control) Unlabeled/Unapproved Uses Disclosure: none Conflicts of Interest: none Background Remote ischemic conditioning (RIC) is a non-invasive strategy to minimize reperfusion injury in ischemic conditions 1

2 Remote Ischemic Conditioning Kharbanda RK et al. Translation of remote ischaemic preconditioning into clinical practice. Lancet 2009;374: Background Recent RCTs suggest no benefit in CABG Previous RCTs suggest a benefit in some surrogate markers for STEMI No meta-analysis or systematic review has assessed the impact of RIC in STEMI as the sole ischemic condition Research Question Does remote ischemic conditioning (RIC) initiated prior to PCI for STEMI reduce reperfusion injury? 2

3 Inclusion Criteria Study Design RCTs published in English Participants STEMI patients, no age restriction Intervention/Comparison RIC prior to balloon inflation (± post RIC) vs PCI alone Outcomes of Interest Primary Outcome Myocardial salvage index (proportion of area at risk of the left ventricle salvaged by treatment following emergent PCI) Secondary Outcomes Infarct size and major adverse cardiovascular events (MACE) Search Strategy Electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials 2 reviewers independently screened titles and abstracts and assessed study quality Hand search of reference lists of relevant articles Grey literature, conference abstracts included 3

4 Methods Data pooled using random-effects models and reported as risk ratios (RR) with 95% confidence intervals (CIs) where appropriate Grading of Recommendations, Assessment, Development and Evaluation criteria used to evaluate quality of evidence Trial Search and Eligibility Process Titles/abstracts acquired from search (n = 643) Titles/abstracts screened (n = 348) Potentially relevant studies retrieved in full text (n = 30) Trials included in systematic review (n = 11) Duplicate articles (n = 295) Articles did not meet eligibility criteria (n = 318) Excluded (n = 19) Kappa = 0.93 (95% CI: 0.81, 1.0) RIC Control Trial Inclusion Criteria RIC Protocol n n Botker 18 years, symptom (2010) 4 5 min cycles of RIC in ambulance onset <12h, STEMI Denmark 3 x 5 min cycles of RIC on arrival to PCI lab (RIC) Eitel 158 RIC and post RIC Symptom onset Followed by 4 x 30 second cycles post stent deployment (post RIC) (2015) 160 <12h STEMI 3 arm trial Germany 173 post RIC RIC alone vs RIC and post RIC vs control (PCI only) Liu STEMI, symptom onset (2016) 4 5 min cycles of RIC in ambulance <12h, 18 years Mongolia Manchurov Acute Myocardial (2014) Infarction 4 5 min cycles of RIC prior to PCI Russia (45 STEMI, 3 NSTEMI) Munk 18 years, symptom (2010) 4 5 min cycles of RIC in ambulance onset <12h, STEMI Denmark Prunier 3 5 min cycles of RIC on arrival 36 RIC 18 years, symptom (2014) 44 onset <6h, STEMI France RIC and post RIC 71 RIC and post RIC 3 4 min cycles of RIC on arrival to hospital Rentoukas 35 to 75 years, 33 RIC (2010) symptom onset RIC with morphine infusion 5 min. prior PCI 30 Greece <6h STEMI 33 RIC and morphine PCI (Sham RIC inflated to a pressure <DBP and saline infusion) Sloth 18 years, symptom (2013) 4 5 min cycles of RIC in ambulance onset <12h, STEMI Denmark Verouhis STEMI, symptom onset 1 x 5 min cycles of RIC on arrival followed by (2016) <6h, 18 years 4 x 5 min cycles of RIC post reperfusion Sweden White 18 to 80 years, 4 5 min cycles of RIC on arrival to hospital (2015) symptom onset UK <12h STEMI PCI alone (uninflated cuff placed on upper arm for 40 min.) Yamanaka 3 5 min cycles of RIC on arrival to hospital 20 years, symptom (2015) onset <24h, STEMI Japan PCI alone (uninflated cuff placed on upper arm for 30 min.) 4

5 Results 11 articles (9 RCTs) included Total of 1,220 individual patients 643 in the RIC+PCI group 577 in the PCI group All 9 RCTs were conducted outside of North America 7 trials used standard manual, BP cuff on the upper limb, 1 lower limb and 1 automated BP cuff for the delivery RIC 2 initiated RIC in the ambulance, 7 RIC initiated on arrival to hospital (prior to PCI) Assessment of Risk of Bias Myocardial Salvage Index RR 0.08 (0.02 to 0.14) 636 5

6 Infarct Size RR (-4.66 to -0.26) 848 (5 studies) MACE 9.5% in the RIC+PCI group compared to 17.0% PCI alone RR 0.57 (0.40 to 0.82) 928 Mortality 4.5% in the RIC+PCI group compared to 7.8% PCI alone RR 0.50 (0.20 to 1.23) 928 6

7 Reinfarction 2.4% in the RIC+PCI group compared to 2.8% PCI alone RR 0.83 (0.38 to 1.82) 928 low Heart Failure 2.2% in the RIC+PCI group compared to 5.4% PCI alone RR 0.41 (0.20 to 0.84) 928 Limitations No North American or non-english studies included Combination of pre- and post-conditioning studies Lack of blinding of participants and personnel (performance bias) Significant loss to follow up for primary end points for imaging studies (attrition bias) Lack of studies focusing on clinically-based outcomes Variable length of follow up for MACE and mortality 7

8 Conclusions RIC appears to be beneficial to infarct size and myocardial salvage index when provided prior to PCI No statistical benefit to death or reinfarction but benefit shown to rates of heart failure at 6 months Findings regarding MACE and clinical outcomes impacted by length of follow up in each study Conclusions RIC is emerging as a promising adjunctive treatment to PCI for the prevention of reperfusion injury in STEMI patients Future multicenter clinical studies will help elucidate the effect of RIC on clinical outcomes such a hospitalization, heart failure and mortality Thank You 8