Search

Irene Sandven,1 Jan Eritsland,2 Michael Abdelnoor3,4 1Oslo Centre for Biostatistics and Epidemiology (OCBE), Oslo University Hospital, Oslo, Norway; 2Department of Cardiology, Oslo University Hospital, Oslo, Norway; 3Centre of Clinical Heart Research, Oslo University Hospital, Oslo, Norway; 4Epidemiology and Biological Statistics, Independent Health Research Unit, Oslo, NorwayCorrespondence: Irene Sandven Email uxsair@ous-hf.noObjective: To evaluate the efficacy of remote ischemic conditioning (RIC) as compared to no conditioning on clinical endpoints in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI).Design: Systematic review of randomized clinical trials (RCTs).Material and Methods: Literature was searched up to September 13, 2019, and we identified a total of 13 RCTs. The efficacy of RIC on incidence of clinical events during follow-up was quantified by the rate ratio (RR) with its 95% confidence interval (CI), and we used fixed and random effects models to synthetize the results. Small-study effect was evaluated, and controlled for by the trim-and-fill method. Heterogeneity between studies was examined by subgroup and meta-regression analyses. The risk of false-positive results in meta-analysis was evaluated by trial sequential analysis (TSA).Results: Pooled analysis of 13 trials (7183 patients) showed that RIC compared to no conditioning revealed a non-significant risk reduction on endpoint mortality (RR=0.81, 95% CI: 0.56– 1.17) during a median follow-up time of 1 year (range: 0.08– 3.8) with low heterogeneity (I2=16%). Controlling for small-study effect showed no efficacy of RIC (adjusted RR: 1.03, 95% CI: 0.66– 1.59). Pooled effect of RIC on the incidence of myocardial infarction (MI) from 11 trials (6996 patients) was non-significant too (RR=0.85, 95% CI: 0.62– 1.18), with no observed heterogeneity (I2=0%) or small-study effect. A similar lack of efficacy was found in endpoint congestive heart failure (CHF) from 6 trials including 6098 patients (RR=0.71, 95% CI: 0.44– 1.15), with moderate heterogeneity (I2=30%). TSAs showed that the pooled estimates from the cumulative meta-analyses were true negative with adequate power.Conclusion: Evidence from this updated systematic review demonstrates no beneficial effect of RIC on the incidence of clinical endpoint mortality, MI and CHF during a median follow-up of 1 year in ACS patients undergoing PCI.Keywords: remote ischemic conditioning, mortality, myocardial infarction, congestive heart failure, meta-analysis, trial sequential analysis

M Abdelnoor,1,2 I Sandven,1 S Limalanathan,3 J Eritsland3 1Centre of Epidemiology and Biostatistics, 2Centre of Clinical Heart Research, 3Department of Cardiology, Oslo University Hospital, Ullevål, NorwayObjective: We aimed to summarize the evidence from randomized clinical trials studies examining the efficacy of ischemic postconditioning (IPost) in ST-elevation myocardial infarction. Design: The study was a systematic review and critical appraisal, with meta-analysis of randomized clinical trials. Materials and methods: We searched the literature. A total of 21 randomized clinical trials were identified. Both fixed effect and random effects models were used to synthesize the results of individual studies. Heterogeneity between studies was examined by subgroup and random effects meta-regression analyses, considering ptient-related and study-level variables. Publication bias, or “small-study effect”, was evaluated. Results: Substantial heterogeneity was present. The random effects model pooled estimate for the outcome infarct size assessed by cardiac magnetic resonance was estimated by the standardized mean difference (SMD) =−0.06, 95% confidence interval (CI): −0.34 to 0.21, ie, no effect of IPost. For the end point infarct size, estimated by biomarkers of myocardial necrosis, an overall pooled effect was SMD =−0.58, 95% CI: −0.96 to −0.19. This effect disappeared in powered and nonbiased studies (SMD =0.03, 95% CI: −0.48 to 0.55). Finally, for the outcome left ventricular ejection fraction, SMD =0.47 95% CI: 0.20 to 0.74. Unfortunately, selection bias (small-study effect) was present. For this outcome, the meta-regression showed that both presence of hypertension and the inclusion of nonbiased studies explained 28.3% of the heterogeneity among the studies. Simulation by the “trim and fill” method, which controlled for selection bias using random effects model, diluted the effect (SMD =0.17 95% CI: −0.13 to 0.48). No effects by IPost on ST-segment resolution or on the majority of adverse clinical events were observed during follow up, except the incidence of congestive heart failure was found. Conclusion: Evidence from this study suggests no cardioprotection from IPost, on surrogate and the majority of clinical end points. A possible beneficial effect on the incidence of congestive heart failure needs to be replicated by a large clinical trial. Keywords: ischemic postconditioning, acute myocardial infarction, percutaneous coronary intervention

Anne H Krog,1,2 Mehdi Sahba,3 Erik M Pettersen,4 Irene Sandven,5 Per M Thorsby,1,6 Jørgen J Jørgensen,1,2 Jon O Sundhagen,2 Syed SS Kazmi2 1Institute of Clinical Medicine, University of Oslo, 2Department of Vascular Surgery, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Oslo, 3Department of Vascular Surgery, Østfold Central Hospital, Fredrikstad, 4Department of Vascular Surgery, Sørlandet Hospital HF, Kristiansand, 5Oslo Center for Biostatistics and Epidemiology (OCBE), 6Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway Purpose: Minimally invasive surgical techniques have been shown to reduce the inflammatory response related to a surgical procedure. The main objective of our study was to measure the inflammatory response in patients undergoing a totally laparoscopic versus open aortobifemoral bypass surgery. This is the first randomized trial on subjects in this population.Patients and methods: This is a substudy of a larger randomized controlled multicenter trial (Norwegian Laparoscopic Aortic Surgery Trial). Thirty consecutive patients with severe aortoiliac occlusive disease eligible for aortobifemoral bypass surgery were randomized to either a totally laparoscopic (n=14) or an open surgical procedure (n=16). The inflammatory response was measured by perioperative monitoring of serum interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP) at six different time points.Results: The inflammatory reaction caused by the laparoscopic procedure was reduced compared with open surgery. IL-6 was significantly lower after the laparoscopic procedure, measured by comparing area under the curve (AUC), and after adjusting for the confounding effect of coronary heart disease (P=0.010). The differences in serum levels of IL-8 and CRP did not reach statistical significance.Conclusion: In this substudy of a randomized controlled trial comparing laparoscopic and open aortobifemoral bypass surgeries, we found a decreased perioperative inflammatory response after the laparoscopic procedure measured by comparing AUC for serum IL-6. Keywords: inflammation, vascular, laparoscopy, surgery, interleukin, C-reactive protein