|Survival and cardiac remodeling benefits in patients undergoing late percutaneous coronary intervention of the infarct-related artery: evidence from a meta-analysis of randomized controlled trials
|Abbate A, Biondi-Zoccai G G, Appleton D L, Erne P, Schoenenberger A W, Lipinski M J, Agostoni P, Sheiban I, Vetrovec G W
This review concluded that late percutaneous coronary intervention of the infarct-related artery >12 hours following acute myocardial infarction may improve survival compared to medical management in stable patients. The review was generally well conducted and the authors’ conclusions appear justified, but differences between studies make the clinical significance of the findings unclear.
To compare percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) with medical therapy in patients randomized >12 hours after acute myocardial infarction (AMI).
Three reviewers independently identified trials through a computerised bibliographic search of PubMed, Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, BioMed Central, Cardiosource, clinicaltrials.gov and ISI Web of Science to July 2007 with no language restrictions. Proceedings from major cardiology meetings from the previous three years were also searched. International experts were queried for additional trials. Search terms were reported.
Only randomised controlled trials comparing late PCI with conservative medical management were eligible for inclusion. Studies were required to include haemodynamic stable patients who had an PCI performed late (>12 hours after onset of symptoms) following an AMI. The mean age was 59 years and men accounted for 77 per cent of patients. The median time from AMI to intervention was 12 days (range 1 to 26 days). Follow up duration ranged from 42 days to 10.2 years (average 2.8 years)
All-cause mortality was the primary outcome. Secondary outcomes included myocardial infarction, repeat revascularisation or rehospitalization for angina or heart failure (HF) at longest follow-up available, while the impact on post-infarction remodeling was assessed by means of changes in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI).
The authors stated neither how the papers were selected for the review nor how many reviewers performed the selection.
Assessment of study quality
The quality of studies was assessed using the Cochrane Collaboration methodology, specifically the following criteria: selection, performance, detection and attrition biases, along with allocation concealment. The authors did not state how the validity assessment was performed.
Data on numbers of events in each group were used to derive the odds ratio for dichotomous outcomes. Continuous variables were reported as mean (SD) or median (range). The authors stated neither how the data were extracted for the review nor how many reviewers performed the data extraction.
Methods of synthesis
For dichotomous outcomes the pooled odds ratio (OR) and corresponding 95% CIs were calculated using the DerSimonian and Laird random-effects model. For continuous outcomes, a random-effect inverse variance model was used. The number needed to treat (NNT) was calculated using random-effect risk differences. Statistical heterogeneity was assessed using the I2 test (high values show increasing heterogeneity). Sensitivity analyses were conducted using a fixed-effect model and meta-regression.
Publication bias was assessed using funnel plots and small study bias was assessed using the Peters' test.
Results of the review
Ten RCTs (n=3,560) were included in the review
Late PCI significantly improved survival compared to medical therapy (10 trials, OR 0.49 (95% CI: 0.26, 0 .94) p=0.030). Statistical heterogeneity was moderate, although sensitivity analyses did not change the results. Late PCI showed non-significant reductions in death or AMI (nine trials, OR 0.70, (95%CI: 0.40, 1.23) p=0.22 ) and in death, recurrent AMI or rehospitalization for angina/heart failure (eight trials, OR 0.66, (95% CI: 0.40, 1.11) p=0.12). Non-fatal MI appeared to be similar in both groups (10 trials, OR 0.86 (95% CI: 0.38, 1.95) p=0.72)
Late PCI was associated with a significant improvement in LVEF over time (seven trials, LVEF +4.4% (95% CI: 1.1, 7.6) p=0.009), change in end diastolic volume (four trials, -7ml/m2 (95% CI: -12.18, -1.81) p=0.008) and change in end-systolic volume (four trials, -7,54ml/m2 (95% CI: -12.61, -2.47) p=0.004) compared with medical therapy. There was evidence of significant statistical heterogeneity. Meta-regression suggested that PCI showed greater benefit in patients with longer follow up time in studies that enrolled patients with total and subtotal occlusions and in studies that did not exclude patients with ischaemia.
There was no evidence of publication bias or small-study bias.
PCI of the IRA performed late (12 hours to 60 days) after AMI is associated with significant improvements in cardiac function and survival compared with medical therapy alone.
This review addressed a clear question in terms of inclusion criteria, study design and outcomes of interest. A number of relevant electronic databases were searched. Search terms were reported. There were no language restrictions. Efforts were made to retrieve unpublished data and publication bias was assessed.
Steps were taken to minimise bias and errors in searching for relevant trials, but methods used to make decisions about the relevance of primary studies, data extraction and quality assessment were not reported. Quality of included trials was measured using Cochrane criteria.
The results reported for the primary outcomes showed significant heterogeneity, which was investigated using sensitivity analyses. Outcomes for cardiac functioning, while statistically significant, showed significant heterogeneity, which was investigated using meta-regression. The authors reported that they performed sensitivity analyses by sequentially omitting individual studies; it would have been helpful to see results for these analyses. Additionally, it appeared that three smaller studies substantially influenced the results. Exclusion of these trials as part of the sensitivity analyses would have been beneficial. Given the significant heterogeneity for most outcomes, the decision to pool studies may not have been appropriate.
The authors' conclusions appeared reasonable given the evidence presented, but the clinical significance was uncertain in view of the differences between studies.
Implications of the review for practice and research
Practice: The authors did not state any implications for practice.
Research: The authors stated that refinement in PCI technology and adjunctive medical therapy was required to improve longevity of PCI patency
Abbate A, Biondi-Zoccai G G, Appleton D L, Erne P, Schoenenberger A W, Lipinski M J, Agostoni P, Sheiban I, Vetrovec G W . Survival and cardiac remodeling benefits in patients undergoing late percutaneous coronary intervention of the infarct-related artery: evidence from a meta-analysis of randomized controlled trials. Journal of the American College of Cardiology 2008; 51(9): 956-964
Subject indexing assigned by NLM
Angioplasty, Transluminal, Percutaneous Coronary; Coronary Vessels /physiopathology; Female; Humans; Male; Myocardial Infarction /drug therapy /mortality /physiopathology /therapy; Randomized Controlled Trials as Topic; Survival Analysis; Time Factors; Treatment Outcome; Ventricular Remodeling
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.