Several recent randomized controlled trials (RCTs) demonstrated better outcomes with multivessel complete revascularization (CR) than with infarct-related artery-only revascularization (IRA-OR) in patients with ST-segment elevation myocardial infarction. It is unclear whether CR should be performed during the index procedure (IP) at the time of primary percutaneous coronary intervention (PCI) or as a staged procedure (SP). Therefore, we performed a pairwise meta-analysis using a random-effects model and network meta-analysis using mixed-treatment comparison models to compare the efficacies of 3 revascularization strategies (IRA-OR, CR-IP, and CR-SP). Scientific databases and websites were searched to find RCTs. Data from 9 RCTs involving 2,176 patients were included. In mixed-comparison models, CR-IP decreased the risk of major adverse cardiac events (MACEs; odds ratio [OR] 0.36, 95% CI 0.25 to 0.54), recurrent myocardial infarction (MI; OR 0.50, 95% CI 0.24 to 0.91), revascularization (OR 0.24, 95% CI 0.15 to 0.38), and cardiovascular (CV) mortality (OR 0.44, 95% CI 0.20 to 0.87). However, only the rates of MACEs, MI, and CV mortality were lower with CR-SP than with IRA-OR. Similarly, in direct-comparison meta-analysis, the risk of MI was 66% lower with CR-IP than with IRA-OR, but this advantage was not seen with CR-SP. There were no differences in all-cause mortality between the 3 revascularization strategies. In conclusion, this meta-analysis shows that in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease, CR either during primary PCI or as an SP results in lower occurrences of MACE, revascularization, and CV mortality than IRA-OR. CR performed during primary PCI also results in lower rates of recurrent MI and seems the most efficacious revascularization strategy of the 3.
Primary percutaneous coronary intervention (PCI) is a standard of care for patients with ST-segment elevation myocardial infarction (STEMI). However, about half the patients with STEMI have obstructive disease in a non–infarct-related artery. Recently, several small-to moderate-sized randomized controlled trials (RCTs) suggested that multivessel (MV) complete revascularization (CR) has better outcomes than infarct-related artery-only revascularization (IRA-OR) in patients with STEMI. Therefore, a recent update was made in the American College of Cardiology Foundation/American Heart Association guidelines for patients with STEMI, recommending CR (either with the index procedure [IP] or as a staged procedure [SP]) as a class IIB indication. Although pathophysiologic and logistic reasons dictate that an MV PCI performed during primary PCI is different from that performed as an SP, no definitive evidence can be found as to whether CR should be performed during the IP at the time of primary PCI or as an SP. All relevant RCTs were either underpowered for comparing the 3 revascularization strategies or compared only 1 type of CR (during IP or as an SP) with IRA-OR. Furthermore, no reports of meta-analyses comparing the 3 revascularization strategies could be found. Therefore, we conducted a network meta-analysis using mixed treatment comparison models and standard pairwise meta-analyses with moderator analyses to compare efficacies of the 3 strategies (IRA-OR, CR during the IP [CR-IP], and CR as an SP [CR-SP]) in patients with STEMI and MV coronary artery disease (CAD).
Methods
This meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. A computerized literature review of PubMed, Google Scholar, and the Cochrane databases was conducted to locate relevant studies. The following keywords were used: “ST-elevation myocardial infarction,” “multivessel,” “complete,” “staged,” “infarct-related artery,” “revascularization,” “percutaneous coronary intervention,” and “randomized controlled trial.” In addition, abstracts from major international cardiology scientific meetings were reviewed. Data were collected on prespecified forms by 2 independent investigators. Disagreements were resolved by consensus. Trials were included if subjects with acute STEMI and MV CAD who underwent primary PCI were enrolled and randomly assigned to either CR or IRA-OR.
The primary efficacy end point was the incidence of major adverse cardiac events (MACEs), defined as the composite of all-cause death (or cardiovascular [CV] death in some studies), myocardial infarction (MI), and urgent/ischemia driven revascularization (or refractory angina in some studies). Secondary efficacy end points were recurrent MI, repeat revascularization CV mortality, and all-cause mortality. The safety outcome was the volume of contrast administered. Study definitions were used for the outcome data.
A traditional pairwise meta-analysis was performed using the Comprehensive Meta-Analysis system, version 3 (Comprehensive Meta-Analysis; Biostat Inc, Englewood, New Jersey). Pooled risk ratios (RRs) were calculated using a random-effects model. The presence of heterogeneity across trials was evaluated using the Cochran Q test and the Higgins I 2 test. The measure of I 2 can be interpreted as the percentage of variability resulting from heterogeneity between studies rather than the sampling error. When heterogeneity was discovered, sensitivity analysis was performed, where 1 study at a time was excluded, and the impact on the summary results of removing each was evaluated. Furthermore, when mixed treatment comparison models (network analysis) showed a statistically significant difference between the CR-IP and CR-SP for any outcome, a direct comparison model using moderator analysis was also performed for those outcomes. Publication bias was not assessed because the number of included trials was inadequate (<10) to properly assess a funnel plot or to use more advanced regression-based assessments.
A Bayesian network meta-analysis was performed using a random-effects model because it is the most conservative method to account for between-trial heterogeneity. All analyses were performed using WinBUGs Bayesian software package and NetMetaXL (Cornerstone Research Group, Burlington, Ontario, L7N 3H8 Canada). We estimated the relative ranking probability of each revascularization strategy and obtained the treatment hierarchy of competing interventions using a league table and surface under the cumulative ranking curve.
In the traditional pairwise meta-analysis, CR was defined as MV revascularization during the IP or as an SP. In the network meta-analysis, patients were divided by revascularization strategy: IRA-OR, CR-IP, and CR-SP. Safety outcome data were summarized as the weighted mean difference (WMD) of contrast use (in ml) with a 95% CI. We used a fixed-effects model in data analysis.
Results
Nine RCTs met the criteria for inclusion; these studies included 2,176 patients. Supplementary Figure S1 shows the search flow diagram. Supplementary Figure S2 shows the network of treatment comparisons. Table 1 describes the characteristics of the individual trials. IRA-OR was compared with CR-IP in 2 RCTs and with CR-SP in 3 RCTs. Two trials compared all 3 revascularization strategies. In 2 trials, all patients underwent CR either during IP or as an SP. Follow-up duration ranged from 6 to 38 months.
