Even in the era of contemporary drug-eluting stents, it is not clear whether percutaneous coronary intervention (PCI) for nonculprit lesions can improve long-term outcomes in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) with multivessel coronary disease. Relevant studies published through August 2014 were searched and identified in the electronic databases. Summary estimates were obtained using a random-effects model. From 368 initial citations, 8 observational studies with 8,425 patients (3,227 multivessel and 5,198 culprit-only PCI) were included. Mean follow-up duration was 18 months. There were no significant differences in all-cause mortality (odds ratios [ORs] 0.85, 95% confidence interval [CI] 0.70 to 1.04) and myocardial infarction (OR 0.86, 95% CI 0.55 to 1.35). However, multivessel PCI was associated with a significantly lower rate of repeat revascularization (OR 0.75, 95% CI 0.56 to 1.00). Comparison of multivessel versus culprit-only PCI disclosed OR for major adverse cardiac events of 0.74 (95% CI 0.57 to 0.97). In conclusion, multivessel PCI reduced repeat revascularization without significant benefits in terms of mortality or myocardial infarction at the long-term follow-up in patients with NSTE-ACS and multivessel coronary disease. Future randomized studies that examine the safety and efficacy of multivessel PCI in NSTE-ACS are warranted.
Approximately half of the patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) present with multiple coronary lesions that may be suitable for interventional treatment. Although early invasive strategy has been shown to improve clinical outcomes compared with conservative strategy and is currently recommended, there is still no formal guidelines of the extent of revascularization for those with multivessel coronary disease. Recently, there has been report of several randomized trials showing better outcomes in the patients with ST-segment elevation myocardial infarction (STEMI) treated with preventive strategy. However, not a few presumed culprit lesions of patients with NSTE-ACS might not have caused the index event, and the interventional cardiologist facing those patients without obvious changes in electrocardiography frequently encounters difficulties in determination of the culprit vessel and decision how to proceed with interventional treatment, as opposed to primary PCI cases in patients with STEMI. Therefore, we performed a systematic review of literature and meta-analyses to compare multivessel complete PCI to culprit-only PCI in patients with NSTE-ACS and multivessel coronary disease.
Methods
We identified relevant studies through electronic searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, ISI Web of Science, Scopus, and Google Scholar databases from January 2001 through August 2014. We have also manually searched the content pages of issues from recent major scientific meetings and performed cross-referencing of review articles to find out further potential publications. Medical subject headings and keyword searches included “multivessel,” “complete,” “staged,” “culprit,” “revascularization,” “angioplasty,” “PCI,” “revascularization,” “unstable angina,” “acute coronary syndrome,” and “myocardial infarction.”
Two investigators (J-SJ and B-HK) independently conducted the literature search, data extraction, and quality assessment using a standardized approach. Selected publications were reviewed by the same investigators to assess whether studies met the inclusion criteria: (1) studies comparing clinical outcomes of multivessel, complete revascularization to those of culprit-only revascularization at the time of index procedure in patients with NSTE-ACS and multivessel coronary disease and (2) follow-up duration ≥6 months. Exclusion criteria were (1) studies comparing PCI with surgical revascularization and (2) studies with lack of control group. The end points of this study were all-cause mortality, myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE) at the longest follow-up.
We calculated odds ratios (ORs) for each outcome using the DerSimonian and Laird random-effects model. Crude OR with 95% confidence interval (CI) was used to assess the efficacy of treatment strategy on adverse clinical events in study populations. All p values were 2 tailed, with statistical significance set at 0.05. We assessed statistical heterogeneity between trials with I 2 statistic, which is derived from Cochran’s Q and the degree of freedom [100 × (Q − df)/Q)]. I 2 values >25%, 50%, and 75% were considered evidence of low, moderate, and severe statistical heterogeneity, respectively. In case of heterogeneity across the studies, we did an influence analysis, in which the pooled estimates were recalculated omitting 1 study at a time, to assess the effect of individual studies on the summary estimate of effect. Publication bias was examined by visual inspection of constructed funnel plot for the all-cause mortality and mathematically by means of Egger’s test and trim-and-fill method.
All statistical analyses were performed using the Review Manager, version 5.1 (The Nordic Cochrane Center, Copenhagen, Denmark) and MIX, version 2.0 (BiostatXL, Sunnyvale, California).
Results
A total of 427 publications were reviewed, and 8 observational studies were selected for inclusion and evaluated ( Figure 1 ). Two large registry studies were excluded because they did not report clinical outcomes after hospital discharge. Characteristics of the included studies are summarized in Table 1 . Of the 8,425 patients, 3,227 patients underwent multivessel PCI and 5,198 underwent culprit-only revascularization at the time of index procedure. Two studies were prospective studies including 3,159 patients and the other 6 studies were retrospective observational studies including 5,266 patients with matched cohorts or consecutive patients comparing multivessel versus culprit-only PCI strategies. Most of the included studies defined MACE as composite of all-cause death, MI, and repeat revascularization except for 2 studies, which included repeat revascularization for ACS and MI requiring hospitalization (excluding periprocedural MI) in their primary end point. More patients of culprit-only PCI group were likely to have a history of PCI in 3 studies ( Table 2 ).
| Study | Year | Study period | Design | PCI strategy ∗ | Primary end point | Exclusion criteria | Follow-up (in months) |
|---|---|---|---|---|---|---|---|
| Brener et al. | 2002 | 1997–1998 | Retrospective, observational | 66/224 | Composite of death, MI, and repeat revascularization for ACS | PCI at non-culprit only | 6 |
| Palmer et al. | 2004 | 2000–2001 | Retrospective, observational | 71/80 | Recurrent angina, repeat PCI or elective CABG, non-fatal MI, death | Previous CABG, LM | 10 |
| Shishehbor et al. | 2007 | 1995–2005 | Prospective, observational | 479/761 | Composite of death, MI requiring hospitalization, or any revascularization | CTOs, staged PCI, prior CABG | 28 |
| Zapata et al. | 2009 | 1996–2006 | Retrospective, observational | 201/404 | MACE, defined as death, MI, or any repeat revascularization | Persistent ST-elevation, CTO, or staged PCI | 12 |
| Kim et al. | 2011 | 2005–2008 | Prospective, observational | 1,011/908 | MACE, defined as all-cause deaths, MI, any repeat revascularization | ST elevation on ECG | 12 |
| Lee et al. | 2011 | 2003–2006 | Retrospective, observational | 179/187 | MACE, defined as the composite of any death, MI, or any revascularization | Prior CABG, LM, CTOs, shock, staged PCI | 36 |
| Onuma et al. | 2013 | 2000–2005 | Retrospective, observational | 611/379 | Composite of all-cause mortality or MI | Prior CABG, staged PCI | 36 |
| Hassanin et al. | 2014 | 2003–2005 | Retrospective, observational | 609/2,255 | MACE, defined as the composite of any cause death, MI, or ischemia-driven PCI | Staged PCI | 12 |
| Study | Age | Male gender (%) | Hypertension (%) | Diabetes (%) | Hyperlipidemia (%) | Smokers (%) | Renal failure (%) | Previous MI (%) | Previous PCI (%) | Previous CVA (%) | Cardiogenic shock (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Brener et al. | 62/62/62 | 71/67/68 | 64/70/69 | 30/27/28 | 68/67/67 | 32/26/27 | NA | 44/43/43 | NA | NA | NA |
| Palmer et al. | 62/63/63 | 69/66/67 | 34/40/37 | 21/21/21 | 82/81/81 | 72/70/71 | NA | 42/37/39 | 17/20/19 | NA | NA |
| Shishehbor et al. | 66/65/65 | 64/65/65 | NA | 32/31/31 | NA | 19/26/23* | 6/6/6 | 46/47/47 | NA | NA | NA |
| Zapata et al. | 61/62/62 | 82/83/83 | 66/65/65 | 20/22/21 | 66/62/63 | 30/31/31 | 3/4/4 | 26/27/27 | 11/17/15 | NA | NA |
| Kim et al. | 65/66/65 | 65/69/67 | 57/60/58 | 34/35/34 | 14/12/13 | 52/55/53 | NA | NA | NA | NA | NA |
| Lee et al. | 65/65/65 | 72/63/67 | 58/63/61 | 34/41/38 | 32/28/30 | 25/19/22 | 6/6/6 | 9/8/8 | 8/16/12* | 9/8/8 | Excluded |
| Onuma et al. | 65/64/65 | 31/30/31 | 44/42/43 | 20/19/20 | 54/54/54 | 23/25/24 | NA | 45/52/48* | 15/33/22* | NA | NA |
| Hassanin et al. | 62/62/62 | 71/72/72 | 69/72/71 | 35/32/33 | 61/64/63 | 31/31/31 | 16/18/18 | 35/38/37 | 46/52/51* | NA | NA |
There was no significant difference in the incidence of all-cause death at follow-up (OR 0.85, 95% CI 0.70 to 1.04) between multivessel PCI and culprit-only PCI group ( Figure 2 ). Statistical heterogeneity was not found in the included studies. Pooled effects showed no significant difference in the incidence of MI at follow-up (OR 0.86, 95% CI 0.55 to 1.35; Figure 2 ). There was evidence of heterogeneity in the included studies. The risk of repeat revascularization was significantly lower in patients who underwent multivessel PCI compared with culprit-only PCI (OR 0.75, 95% CI 0.56 to 1.00; Figure 2 ). There was statistically significant heterogeneity in the included studies.
The incidence of MACE was significantly lower in the multivessel PCI group compared with culprit-only PCI group (OR 0.74, 95% CI 0.57 to 0.97; Figure 3 ). Statistically significant heterogeneity was noted in the included studies. The sensitivity analysis of the risk of MACE with multivessel PCI by excluding studies and repeating meta-analysis shifted ORs to rightward offsetting the statistically significant benefit of multivessel PCI over culprit-only PCI ( Supplementary Figure 1 ). The cumulative analysis of the included studies up to a time point in a chronological order depicts the summary ORs of recently published studies favoring multivessel PCI ( Supplementary Figure 2 ).
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