American College of Cardiology/American Heart Association guidelines for management of patients with ST-segment elevation myocardial infarction (STEMI) recommend culprit artery-only revascularization (CULPRIT) based on safety concerns during noninfarct-related artery intervention. However, the data to support this safety concern are scant. Searches were performed in PubMed/EMBASE/CENTRAL for studies evaluating multivessel revascularization versus CULPRIT in patients with STEMI and multivessel disease (MVD). A multivessel revascularization strategy had to be performed at the time of CULPRIT or during the same hospitalization. Early (≤30-day) and long-term outcomes were evaluated. Among 19 studies (23 arms) that evaluated 61,764 subjects with STEMI and MVD, multivessel revascularization was performed in a minority of patients (16%). For early outcomes, there was no significant difference for outcomes of mortality, MI, stroke, and target vessel revascularization, with a 44% decrease in risk of repeat percutaneous coronary intervention and major adverse cardiovascular events (odds ratio 0.68, 95% confidence interval 0.57 to 0.81) with multivessel revascularization compared to CULPRIT. Similarly, for long-term outcomes (follow-up 2.0 ± 1.1 years), there was no difference for outcomes of MI, target vessel revascularization, and stent thrombosis, with 33%, 43%, and 53% decreases in risk of mortality, repeat percutaneous coronary intervention, coronary artery bypass grafting, respectively, and major adverse cardiovascular events (odds ratio 0.60, 95% confidence interval 0.50 to 0.72) with multivessel revascularization compared to CULPRIT. In conclusion, in patients with STEMI and MVD, multivessel revascularization appears to be safe compared to culprit artery-only revascularization. These findings support the need for a large-scale randomized trial to evaluate revascularization strategies in patients with STEMI and MVD.
Primary percutaneous coronary intervention (PCI) is currently the reperfusion treatment of choice in acute ST-segment elevation myocardial infarction (STEMI). In patients with an acute coronary syndrome, 30% to 60% have multiple coronary lesions, attesting to the diffuse nature of the atherosclerotic process. Outcomes in patients with STEMI and multivessel disease (MVD) are significantly worse than for those with 1-vessel disease. American College of Cardiology/American Heart Association STEMI guidelines recommend treatment of the culprit artery-only revascularization (CULPRIT) only during PCI, and as such PCI of noninfarct-related artery is not recommended (class III), although the level of evidence is C (expert opinion). However, there are exceptions and multivessel PCI is not contraindicated in patients with hemodynamic compromise, although the guidelines do not explicitly recommend it. The guidelines are also silent on the management of remaining MVD, i.e., staged revascularization versus medical management versus ischemia-driven revascularization strategies. As a result the practicing physician is left with no definitive guidelines, leading to ambiguity and variability in practice patterns, but incomplete revascularization is the norm. The guidelines seem to be based on safety concerns for PCI of a noninfarct-related artery. However, the data to support this are scant. Our objective was to evaluate the efficacy and safety of multivessel revascularization compared to CULPRIT strategy in patients with STEMI and MVD.
Methods
We conducted PubMed/EMBASE/CENTRAL searches of studies using the terms “complete revascularization,” “multivessel revascularization,” “culprit revascularization,” “culprit-only revascularization,” and “myocardial infarction.” We limited our search to studies in humans from 1966 through May 2010. We checked reference lists of review articles, meta-analyses, and original studies identified by the electronic search to find other potentially eligible studies. There was no language restriction. Authors of studies were contacted when results were unclear or when relevant data were not reported. We also searched conference proceedings of all major national and international cardiovascular societies.
Eligible studies had to fulfill the following criteria to be included in this analysis: (1) studies of subjects with STEMI and MVD, (2) multivessel revascularization done within the same hospitalization, and (3) studies that reported outcomes of interest. We excluded studies that evaluated only patients with cardiogenic shock.
Two authors (S.B. and S.K.) independently and in duplicate assessed trial eligibility, quality, and extracted data. Disagreements were resolved by consensus. Quality of studies was assessed using methods recommended by the Cochrane Collaboration based on the following 6 components: (1) sequence generation of allocation; (2) allocation concealment; (3) blinding of participants, personnel, and outcome assessors; (4) incomplete outcome data; (5) selective outcome reporting; and (6) other sources of bias. Of note, only 2 randomized trials fulfilled our inclusion criteria. For nonrandomized studies, quality was assessed based on completeness of reporting, reporting of adjusted risk of outcomes, use of propensity adjustment, or absence of differences between reported baseline variables in the 2 groups—representing higher-quality studies.
Outcomes of interest were early (≤30-days) and long-term efficacy and safety outcomes. For early outcomes, we evaluated death, MI, stroke, stent thrombosis, repeat PCI, coronary artery bypass grafting, target vessel revascularization, contrast-induced nephropathy, major adverse cardiovascular events (MACEs), and length of hospital stay. For long-term outcomes, we evaluated death, MI, stroke, repeat PCI, coronary artery bypass grafting, target vessel revascularization, and MACEs.
Meta-analysis was performed in line with recommendations from the Cochrane Collaboration and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) statement using standard software (STATA 9.0, STATA Corporation, College Station, Texas). Heterogeneity was assessed using I 2 statistics. I 2 is the proportion of total variation observed between studies attributable to differences between studies rather than sampling error (chance), with I 2 <25% considered low and I 2 >75% high. We used the Peto method for calculating effect sizes. Bias was estimated visually by funnel plots and/or using the Begg test and weighted regression test of Egger.
Analyses were performed based on the strategy used for multivessel revascularization: (1) 1 setting, namely when multivessel revascularization was performed during CULPRIT and (2) staged PCI namely when multivessel revascularization was performed as staged in-hospital revascularization. If any results were significant, we estimated the difference between estimates of subgroups according to tests of interaction. A p value <0.05 indicates that effects of treatment differ between tested subgroups.
A sensitivity analysis was performed using high-quality studies defined as (1) randomized trials; (2) studies without significant differences in reported baseline variables; (3) studies that reported adjusted risk; or (4) studies that used propensity-score matching to adjust for baseline imbalances between 2 groups.
Results
Among the 548 articles identified through the search, 19 studies (23 arms) fulfilled our inclusion criteria ( Figure 1 ). Data from Rha et al were an updated analysis that was obtained from personal communication from Dr. Rha. Of 19 studies, only 2 were randomized trials. We excluded the staged (out of hospital) revascularization arm of studies by Politi et al and Hannan et al, only 2 studies used propensity-score matching, and for these studies outcomes reported in the matched cohort were used. A study by Grantham included patients with STEMI and those with non-STEMI but most (64%) had STEMI.
The 19 studies (23 arms) evaluated 61,764 patients with STEMI and MVD. Multivessel revascularization was performed in 9,690 patients (16%), and the remaining 52,074 patients (84%) underwent CULPRIT during index hospitalization. Baseline characteristics of studies are presented in Tables 1 and 2 . Table 3 lists baseline characteristics, presentation details, and angiographic features between the multivessel group and the CULPRIT group. All variables were weighted based on the weight of each trial. There were larger proportions of men and those who presented with heart failure in the multivessel group but a smaller proportion of patients with diabetes or previous coronary artery bypass grafting compared to CULPRIT. Other characteristics were similar between the 2 groups ( Table 3 ).
| Study | Year | Subjects | Age (years) | Men | Cardiogenic Shock | Killip Class 3/4 | Diabetes | Follow-up (months) | Multivessel Revascularization Setting | |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 Setting | Staged | |||||||||
| Corpus et al | 2004 | 506 | 63 | 69% | 3.4% | — | 17% | 12 | + | + |
| Grantham | 2006 | 291 | 61 | 73% | 0% | 4.8% | 22% | 6 | 0 | + |
| Hannan et al | 2010 | 1524 | — | 80% | 0% | — | 22% | 42 | + | + |
| HELP-AMI | 2004 | 69 | 64 | 87% | 0% | 18.8% | 19% | 12 | + | 0 |
| Hudzik | 2009 | 2099 | 64 | 57% | 12% | 11.8% | 26% | 36 | 0 | + |
| Kalarus et al | 2007 | 786 | 61 | 71% | 10% | 10.0% | 33% | 30 | + | + |
| KAMIR | 2009 | 804 | 63 | 75% | 0% | 6.0% | 28% | 8 | + | 0 |
| Khattab et al | 2008 | 73 | 66 | 77% | 4% | — | 12% | 12 | + | 0 |
| MEDPAR | 2010 | 24,106 | — | 60% | — | — | — | 0 | + | 0 |
| NCDR ⁎ | 2009 | 25,847 | 61 | 72% | 0% | — | 24% | 0 | + | 0 |
| NYS Angioplasty Registry † | 2006 | 1982 | 61 | 74% | 0% | 7.5% | 19% | 0 | + | 0 |
| Politi et al ‡ | 2010 | 149 | 65 | 77% | 0% | — | 19% | 30 | + | 0 |
| Qarawani et al | 2007 | 120 | 66 | 65% | 0% | 22.5% | 13% | 12 | + | 0 |
| Rahman et al | 2010 | 2077 | — | — | — | — | — | 12 | + | 0 |
| Rigattieri et al | 2008 | 110 | 66 | 75% | 0 | — | 23% | 13 | 0 | + |
| Roe et al | 2001 | 158 | 63 | 71% | 28% | 33.2% | 33% | 6 | + | 0 |
| Seo et al | 2009 | 299 | — | — | — | — | — | 48 | + | 0 |
| Telayna | 2002 | 113 | 60 | 85% | 0 | 8.8% | 19% | 6 | + | 0 |
| Varani et al | 2008 | 399 | 69 | 71% | — | 10.6% | 16% | 21 | + | + |
⁎ Cohort without cardiogenic shock.
† According to investigator, study included mostly patients with ST-segment elevation myocardial infarction and few with non–ST-segment elevation myocardial infarction.
‡ Data excludes the staged complete revascularization cohort.
| Study | Inclusion | Exclusion | Type of Study |
|---|---|---|---|
| Corpus et al | AMI and MVD defined as ≥70% stenosis of ≥2 epicardial coronary arteries or their major branches | PCI of vein graft, left main coronary artery, acute occlusion after angioplasty, and staged PCI of non-IRA after hospital discharge | nonrandomized |
| Grantham | AMI and MVD defined as ≥70% stenosis of ≥2 epicardial coronary arteries or their major branches | — | nonrandomized |
| Hannan et al | AMI and MVD | those with missing ejection fraction, left main coronary artery disease, previous bypass surgery, shock, or thrombolytic therapy | propensity-score matched |
| HELP-AMI | AMI and MVD | vein graft or arterial conduit disease, in-stent restenosis, recent thrombolysis, cardiogenic shock; left main coronary artery stenoses ≥50% | randomized |
| Hudzik | AMI and MVD | — | nonrandomized |
| Kalarus et al | AMI and MVD defined as ≥70% stenosis of ≥2 epicardial coronary arteries or their major branches | — | nonrandomized |
| KAMIR | AMI and MVD | — | propensity-score matched |
| Khattab et al | AMI and MVD defined as ≥70% stenosis of ≥2 major epicardial vessel/branches | previous MI, significant left main coronary artery disease, artery diameter <2.5 mm or totally occluded, or having extensive calcification | nonrandomized |
| MEDPAR | patients who underwent PCI during a hospitalization with primary diagnosis of STEMI | — | nonrandomized |
| NCDR ⁎ | patients with STEMI and found to have coronary artery disease in >1 major artery | PCI of left main coronary artery or thrombolytics | nonrandomized |
| NYS Angioplasty Registry † | AMI and MVD defined as ≥70% stenosis of ≥2 epicardial coronary arteries or their major branches | cardiogenic shock, cardiopulmonary resuscitation, left main coronary artery stenosis >50%; previous MI, PCI, or CABG | nonrandomized |
| Politi et al ‡ | AMI and MVD defined as ≥70% stenosis of ≥2 epicardial coronary arteries or their major branches | cardiogenic shock, left main coronary artery disease, previous CABG, severe valvular heart disease, and unsuccessful procedure | randomized |
| Qarawani et al | AMI and MVD defined as ≥70% stenosis of ≥2 epicardial coronary arteries or their major branches | patients with cardiogenic shock and presence of left main coronary artery stenosis ≥50% | nonrandomized |
| Rahman et al | patients with STEMI who underwent PCI and had MVD | — | nonrandomized |
| Rigattieri et al | AMI and MVD | cardiogenic shock at presentation, left main coronary artery disease, previous bypass surgery, and severe valvular heart disease | nonrandomized |
| Roe et al | AMI and MVD defined as ≥50% stenosis of ≥1 nonculprit artery in addition to culprit lesion | patients who underwent PCI of branch vessels of IRA or left main coronary artery | nonrandomized |
| Seo | AMI and MVD | — | nonrandomized |
| Telayna | AMI and MVD | patient with Killip class IV and 1-vessel disease | nonrandomized |
| Varani et al | AMI and MVD defined as ≥50% stenosis of ≥1 nonculprit artery in addition to culprit lesion | PCI for acute occlusion after coronary angioplasty | nonrandomized |
⁎ Cohort without cardiogenic shock.
† According to investigator, study included mostly patients with ST-segment elevation myocardial infarction and few with non–ST-segment elevation myocardial infarction.
‡ Data excludes the staged complete revascularization cohort.
| Variable | Multivessel Revascularization | Culprit-Only Revascularization | p Value |
|---|---|---|---|
| (n = 9,690) | (n = 52,074) | ||
| Age (years) | 62.4 ± 2.1 | 62.1 ± 2.7 | 0.731 |
| Men | 66.7% | 63.9% | 0.031 |
| Diabetes mellitus | 22.7% | 25.5% | 0.047 |
| Hypertension | 59.2% | 59.2% | 0.971 |
| Hyperlipidemia | 56.2% | 54.0% | 0.657 |
| Previous myocardial infarction | 17.6% | 18.3% | 0.806 |
| Previous percutaneous coronary intervention | 15.7% | 13.7% | 0.401 |
| Previous coronary artery bypass grafting | 4.0% | 7.1% | 0.037 |
| Chronic renal insufficiency | 5.2% | 5.4% | 0.909 |
| Known heart failure | 7.1% | 4.9% | 0.462 |
| Previous cerebrovascular accident | 6.8% | 6.8% | 0.973 |
| Smoking | 60.1% | 58.4% | 0.664 |
| Presentation | |||
| Cardiogenic shock | 3.5% | 4.6% | 0.607 |
| Heart failure at admission | 11.8% | 9.1% | 0.012 |
| Ejection fraction | 44.0 ± 4.1 | 42.0 ± 3.3 | 0.297 |
| Killip class 3/4 heart failure | 11.4% | 10.6% | 0.659 |
| Angiographic characteristics | |||
| Left anterior descending coronary artery stenosis | 27.7% | 26.4% | 0.743 |
| 3-vessel coronary disease | 27.0% | 35.8% | 0.258 |
| Glycoprotein IIb/IIIa inhibitor use | 42.5% | 45.5% | 0.854 |
| Stent usage | 90.0% | 82.4% | 0.330 |
| Drug-eluting stent usage | 39.4% | 39.7% | 0.993 |
All comparisons reported are for multivessel revascularization compared to CULPRIT. There was no significant difference in early mortality for the overall cohort ( Figure 2 ), with increased mortality in the 1-setting cohort but decreased mortality in the staged cohort with multivessel revascularization compared to CULPRIT (p for interaction <0.001). There was significant heterogeneity, driven mainly by the 1-setting studies ( Figure 2 ). There was no difference in early MI for the overall cohort (odds ratio [OR] 1.74, 95% confidence interval [CI] 0.94 to 3.20) or the 1-setting cohort (OR 0.56, 95% CI 0.25 to 1.27) but increased risk of MI with multivessel revascularization compared to CULPRIT for the staged revascularization cohort (OR 7.52, 95% CI 2.97 to 19.02, p for interaction < 0.0001), driven by a study by Corpus et al. There was no difference in early stroke (OR 0.97, 95% CI 0.62 to 1.53) or early target vessel revascularization (OR 0.83, 95% CI 0.44 to 1.58) for the overall cohort and the interaction by setting (1 setting vs staged) was negative (p for interaction = 0.06 and 0.86, respectively). There was a 44% decrease in the odds of early repeat PCI (OR 0.56, 95% CI 0.32 to 0.98) and a 46% decrease in the odds of early coronary artery bypass grafting (OR 0.54, 95% CI 0.40 to 0.73) with multivessel revascularization for the overall cohort and interaction by setting (1 setting vs staged) was negative (p for interaction = 0.58 and 0.24, respectively). However, there was a 27% increase in the odds of contrast-induced nephropathy with multivessel revascularization for the overall cohort (OR 1.27, 95% CI 1.12 to 1.45), an increased risk with 1 setting (OR 1.29, 95% CI 1.13 to 1.47), but a decreased risk with staged revascularization (OR 0.09, 95% CI 0.01 to 0.64, p for interaction <0.0001). The increase risk was driven largely by the Medicare Provider analysis and Review (MEDPAR) study (83% weight). Exclusion of this study failed to show a significant difference in outcome of contrast-induced nephropathy between the 2 groups. There was a 32% decrease in the risk of early MACEs with multivessel revascularization for the overall cohort ( Figure 2 ) and interaction by setting (1 setting vs staged) was negative (p of interaction = 0.27). However, there was no difference in the length of stay between the 2 groups (p = 0.37).
