Key PointsQuestion
In patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease, does a strategy of complete revascularization improve angina-related quality of life compared with culprit lesion–only percutaneous coronary intervention?
Findings
In this secondary analysis of a randomized clinical trial of 4041 patients, angina status improved in both revascularization groups. More patients were free of angina in the complete revascularization compared with the culprit lesion–only percutaneous coronary intervention group.
Meaning
A complete revascularization strategy resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion–only strategy; this modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.
Importance
In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion–only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown.
Objective
To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD.
Design, Setting, and Participants
This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021.
Interventions
Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization.
Main Outcomes and Measures
Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end.
Results
Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion–only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion–only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion–only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02).
Conclusions and Relevance
In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion–only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.
Multivessel coronary artery disease (CAD) is common in patients presenting with ST-segment elevation myocardial infarction (STEMI).1 The goals of treatment for these patients are to reduce morbidity and mortality and to alleviate symptoms and improve quality of life. Several randomized clinical trials have established that a strategy of complete revascularization in STEMI reduces cardiovascular events largely due to reduced rates of ischemia-driven revascularization.2-5 Recently, the Complete vs Culprit-Only Revascularization Strategies to Treat Multivessel Disease After Early Percutaneous Coronary Intervention (PCI) for STEMI (COMPLETE) trial (NCT01740479) demonstrated that, among 4041 patients with STEMI and multivessel CAD, a strategy of complete revascularization with multivessel PCI reduced the composite of cardiovascular death or new myocardial infarction, with a number needed to treat of 37 to prevent 1 major event.6 Based on these data, the 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization recommend complete revascularization with staged PCI as a class 1A recommendation to reduce the risk of death or myocardial infarction (MI) in selected patients with STEMI and multivessel CAD.7
The effect of complete revascularization on patient-reported outcomes such as angina-related quality of life remains uncertain.8,9 In particular, there have been no randomized clinical trials evaluating the effect of a complete revascularization strategy on quality of life, to our knowledge. To address this gap in knowledge, we prospectively evaluated angina-related quality of life in the COMPLETE trial to define the association of complete revascularization with quality of life in patients with STEMI and multivessel CAD.
COMPLETE was a multinational randomized clinical trial evaluating a strategy of complete revascularization with PCI of all suitable nonculprit lesions vs a strategy of culprit lesion–only PCI in patients with STEMI and multivessel CAD who had undergone successful culprit lesion PCI from 140 primary PCI centers in 31 countries.6,10 Patients presenting to an enrolling hospital with STEMI were eligible if they had multivessel CAD, defined as the presence of at least 1 additional noninfarct-related lesion with stenosis severity of 70% or more (or 50%-69% with fractional flow reserve ≤0.80), diameter of 2.5 mm or more, and amenable to successful treatment with PCI. Patients with planned or prior surgical revascularization were excluded. All patients provided written informed consent to participate and research ethics board approval was obtained in all participating centers. The trial protocol is available in Supplement 1.
Patients were randomized between February 1, 2013, and March 6, 2017. Eligible patients were randomly assigned to either complete revascularization or a culprit lesion–only strategy according to a computer-generated randomization list using permuted random block sizes blinded to centers. Patients randomized to complete revascularization were to have routine staged PCI (ie, PCI during a separate sitting from the index PCI for STEMI) of all suitable nonculprit lesions irrespective of whether there were clinical symptoms or there was evidence of ischemia. Everolimus-eluting stents were strongly recommended for both index and nonculprit lesion PCI procedures. It was recommended that PCI of chronic total occlusions be attempted only by experienced chronic total occlusion operators and only if there was a high likelihood of PCI success. Patients who were randomized to the culprit lesion–only strategy received guideline-directed medical therapy alone, with revascularization of nonculprit lesions permitted only if 1 of the following specific crossover criteria was met: (1) recurrent MI, (2) hemodynamic instability, (3) refractory ischemic heart failure (defined as Killip class ≥3), or (4) intractable angina (Canadian Cardiovascular Society class 3 or 4 symptoms) despite optimal medical therapy and documented evidence of ischemia in a territory supplied by a vessel having a nonculprit lesion.
Guideline-directed medical therapy was recommended in both randomized groups and included dual antiplatelet therapy with aspirin and ticagrelor for at least 1 year, high-dose statin therapy, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, mineralocorticoid inhibitors, and β-blockers.
Health-Related Quality of Life
CAD-related health status was assessed using the Seattle Angina Questionnaire (SAQ).11 This 19-item questionnaire assesses frequency of angina, treatment satisfaction, angina stability, physical limitation, and quality of life. Scores range from 0 to 100 for each domain, with higher scores indicating better disease-specific health status and fewer symptoms. The angina frequency domain quantifies the frequency and burden of angina over the previous 4 weeks. SAQ angina frequency (SAQ-AF) scores of 0 to 30, 31 to 60, 61 to 99, and 100 signify angina that occurred daily, weekly, monthly, or not at all over the past 4 weeks, respectively.12 The physical limitation domain measures how daily activities are limited by symptoms of CAD. The treatment satisfaction domain quantifies patients’ satisfaction with current treatment of their CAD. The quality of life domain expresses how the patient perceives angina to be impacting their quality of life.
The SAQ was given to participants at the time of randomization or shortly thereafter (baseline), 6 months after randomization, and at their final visit, which occurred at a median (IQR) of 35.8 (27.6-44.3) months after randomization. Questionnaires were administered in person or by mail using linguistically and culturally validated translations in each participant’s native language. The primary analyses were the score on the SAQ-AF domain and the proportion of patients free from angina (defined as an SAQ-AF score of 100). In addition, scores on the physical limitation and quality of life domains of the SAQ were evaluated. The SAQ summary score, a mean of the angina frequency, physical limitation, and quality of life scores, was used as an overall measure of patients’ angina-related health status.
Total angina burden over the course of the trial was defined as the binary composite of any outcome requiring the presence of angina or ischemic symptoms as a key part of its definition (MI, ischemia-driven revascularization, or unstable angina) or residual angina at study end (defined as an SAQ-AF score <100). Protocol definitions of these outcomes are available in eTable 1 in Supplement 2.
All randomized patients were included in the analysis according to the treatment group to which they were assigned (intention-to-treat principle). Patient characteristics, SAQ domain scores, and freedom from angina at baseline were summarized with means (SDs) for continuous variables and frequency and percentage for categorical variables according to treatment allocation.
SAQ scores at 6 months and final follow-up were reported as means (SDs) and compared between the 2 treatment arms using a mixed-model-for-repeated-measures analysis, where missing SAQ data were assumed missing at random. In the mixed model, we included treatment, visit time, interaction of treatment and visit time, and intended timing of complete revascularization (stratification factor for randomization), where visit time was treated as a nominal variable. Parameters were estimated using the restricted maximum likelihood method with an unstructured covariance matrix. The difference between the 2 treatment groups and corresponding 95% CIs were reported. To assess the robustness of results, 3 sensitivity analyses were performed (eMethods in Supplement 2): treating visit time as a continuous variable, adjusting for baseline SAQ, and using multiple imputation to impute missing data (eTables 2-4 in Supplement 2).
Freedom from angina at baseline and follow-up visits was defined as having an SAQ-AF score of 100. The proportion of patients free of angina at 6 months and final follow-up was compared between the 2 randomized groups with a generalized linear mixed model to account for the underlying correlation between different measures within individual patients.
Total angina burden over the course of the trial was assessed by the composite of angina-associated cardiovascular events (MI, ischemia-driven revascularization, or unstable angina) or residual angina at study end (SAQ-AF score <100) using a logistic regression model. The absolute risk difference and 95% CIs were reported.
To explore the heterogeneity of treatment effects on the SAQ-AF score with respect to prespecified baseline patient characteristics, mixed model for repeated measures analysis was used to evaluate heterogeneity of treatment effects at different time points. The model was identical to the primary model, with the addition of a term for the 3-way interaction among treatment, visit, and subgroup. Prespecified subgroups analyzed were prerandomization intent to perform staged nonculprit lesion PCI during index hospitalization or after discharge (stratification variable), proximal or mid left anterior descending coronary artery nonculprit lesion (yes/no), nonculprit lesion diameter stenosis severity of 80% or more by visual estimation or, if visual estimate was not available, 60% or more by core laboratory quantitative coronary angiography analysis (yes/no), residual SYNTAX score (greater than or less than median), diabetes (yes/no), and baseline SAQ-AF score prior to the qualifying STEMI (daily/weekly, monthly, or none). The difference between the 2 treatment groups with 95% CIs and interaction P values was reported in each subgroup.
A 2-sided P < .05 was considered statistically significant without correction for multiple comparisons. All statistical analyses were performed with the use of SAS 9.4 software (SAS Institute). Analysis took place between July 2021 and December 2021.
A total of 4041 patients were randomized: 2016 to complete revascularization and 2025 to culprit lesion–only PCI. Over the entire trial duration, crossover from the culprit lesion–only strategy to complete revascularization occurred in 391 patients (19.3%) and from complete revascularization to culprit lesion–only PCI in 135 (6.7%) (Figure 1). Approximately 266 patients (13%) in the culprit lesion-only PCI arm received nonculprit lesion PCI associated with MI, ischemia-driven revascularization, or unstable angina (eFigure in Supplement 2).
SAQ-AF scores were available in 1095 patients (94.5%) in the complete revascularization group and 1925 (95.1%) in the culprit lesion–only group at baseline, in 1734 (87.5%) and 1730 (86.7%) at 6 months, and in 1666 (86.8%) and 1632 (85.0%) at final follow-up, which occurred at a median of 3 years after randomization (Figure 1). Baseline characteristics and disease-specific health status are shown in Table 1. The mean (SD) age of patients was 62 (10.7) years, 3225 (80%) were male, and 787 (19%) had diabetes. The mean (SD) baseline score on the SAQ-AF scale (reflecting health status prior to the qualifying STEMI) was not significantly different between the groups (87.1 [17.8] vs 87.2 [18.4], in the complete and culprit lesion–only revascularization groups, respectively). In the complete revascularization and culprit lesion-only groups, 245 patients (12.9%) and 250 patients (13.0%) had daily/weekly angina, 719 (37.7%) and 675 (35.1%) had monthly angina, and 941 (49.4%) and 1000 (51.9%) had no angina in the month before randomization.
At a median of 3 years of follow-up, the mean (SD) score on the SAQ-AF scale was 97.1 (9.7) points in the complete revascularization group (9.8 [18.9]-point increase from baseline; score change, 9.9 [95% CI, 9.0-10.8]; P < .001), compared with 96.3 (10.9) points in the culprit lesion–only group (8.6 [19.9]-increase from baseline; score change, 8.9 [95% CI, 8.0-9.8]; P < .001), for a mean between-group difference of 0.97 points (95% CI, 0.27-1.67; P = .006). The quality of life and physical limitation scores were also greater in the complete revascularization group compared with the culprit lesion–only group at follow-up (Table 2). The SAQ summary score, an overall measure of angina-related health status, also increased to a greater degree in the complete revascularization group compared with the culprit lesion–only group at 6 months (mean difference, 1.35 [95% CI, 0.40-2.31]; P = .006) and at final follow-up (mean difference, 1.27 [95% CI, 0.44-2.11]; P = .003). Sensitivity analyses treating time as continuous variable demonstrated similar results to the primary analysis (eTable 2 in Supplement 2) as did adjusting for baseline SAQ score (eTable 3 in Supplement 2) and analyses to account for missing data using multiple imputation (eTable 4 in Supplement 2).
At 6 months, 1350 patients (77.9%) in the complete revascularization group were free of angina (SAQ-AF score, 100) compared with 1312 patients (75.8%) in the culprit lesion–only group (absolute difference, 1.99% [95% CI, −1.09 to 5.08%]; P = .21). At a median of 3 years of follow-up, 1457 patients (87.5%) in the complete revascularization group were free of angina compared with 1376 patients (84.3%) in the culprit lesion–only group (absolute difference, 3.21% [95% CI, 0.69-5.73%]; P = .01). This translates into a number needed to treat of 31 patients (95% CI, 17-145) receiving complete revascularization for 1 additional patient to be angina free at 3 years compared with patients receiving a culprit lesion–only PCI strategy.
There was no differential treatment effect in predefined subgroups, except for nonculprit lesion stenosis severity (Figure 2A and B). There was an apparent greater benefit of complete revascularization in patients with nonculprit lesion stenosis severity of 80% or more by visual estimation (or ≥60% by core laboratory analysis) for both mean the SAQ-AF score (interaction P = .05) and proportion of patients free of angina at follow-up (interaction P = .02). For patients with nonculprit lesion stenosis severity of 80% or more by visual estimation (or ≥60 by core laboratory analysis), the mean between-group difference in SAQ-AF score was 1.29 points (95% CI, 0.51-2.06), while in those with stenosis severity less than 80% (or <60% by core laboratory analysis), the mean between-group difference was −0.50 points (95% CI, −2.14 to 1.13). Similarly, in those with nonculprit lesion stenosis severity of 80% or more visual (or ≥60% by core laboratory analysis), the mean between-group difference in proportion free of angina at study end was 4.71% (95% CI, 1.95-7.48) favoring complete revascularization, whereas in those with stenosis severity less than 80% visual (or <60% by core laboratory analysis), the mean between-group difference was −3.16% (95% CI, −8.69 to 2.37).
Total angina burden over the course of the trial, defined as the composite of angina-associated cardiovascular events (MI, ischemia-driven revascularization, unstable angina) or residual angina at last follow-up (SAQ-AF score <100), was lower in the complete revascularization group compared with the culprit lesion–only strategy (467 [28.6%] vs 330 [19.8%]; absolute risk difference, 8.99% [95% CI, 6.03-12.0]; P < .001) (Figure 3). Guideline-directed medical therapy over the course of the trial is shown in eTable 5 in Supplement 2.
The main results of the COMPLETE trial demonstrated that in patients with STEMI and multivessel CAD, complete revascularization with angiographically guided nonculprit lesion PCI reduced major cardiovascular events compared with a strategy of culprit lesion–only PCI. In this prespecified analysis from the COMPLETE trial, we present the association of complete revascularization with patient-reported quality of life outcomes as they relate to angina status. First, we found that about half of patients presenting with STEMI and multivessel CAD did not have angina prior to their index STEMI event. In spite of this, angina status improved in both revascularization groups compared with baseline, with a slightly greater proportion of patients being free of angina in the complete revascularization group than in the culprit lesion–only group at a median follow-up of 3 years. This benefit was observed almost entirely in those with more severe nonculprit lesions (diameter stenosis ≥80% visual or ≥60% quantitative coronary angiography), with no apparent benefit in those with less severe lesions. Finally, when residual angina at study end was considered in the context of total angina burden over the 3-year course of the trial, there was a more marked absolute benefit of complete revascularization.
Our findings extend insights on the effects of revascularization from trials of stable angina to the setting of STEMI.13-15 In some trials of PCI vs medical therapy for stable angina, there was a differential treatment effect of complete revascularization, where patients with more frequent baseline angina had greater treatment effect. We did not observe a significant interaction in the COMPLETE trial, although the absolute benefit in terms of angina-free status appeared greater in those with daily angina at baseline (absolute difference, 5.55%) than in those with no baseline angina (absolute difference, 2.52%). Symptoms in the setting of STEMI are often new-onset secondary to acute plaque rupture or erosion of the culprit lesion, whereas in stable CAD, angina is often longstanding due to chronic stenoses. Thus, the proportion of patients who were angina-free prior to enrollment was much higher in the COMPLETE trial than in previous revascularization trials of stable CAD.15-18 Also, in trials of stable angina, patients allocated to medical management do not receive routine protocol mandated PCI, whereas in the COMPLETE trial, all patients in both arms of the trial had primary PCI of the culprit lesion, thus removing the contribution of the culprit lesion itself to subsequent angina burden equally in both treatment groups. Finally, over the median 3-year course of the trial, it is also possible there was greater progression in severity of nonculprit lesion disease in the culprit lesion–only PCI group in keeping with the natural history of CAD. The complete revascularization group would have been protected from nonculprit lesion disease progression because nonculprit lesions in this group were treated with PCI.
Importantly, the SAQ-AF score improved substantially in both randomized groups from baseline to follow-up. When the SAQ-AF score was analyzed as a continuous variable (ie, a population-based mean score in each group), the difference between the groups was statistically significant but appeared relatively small, in part because about half of the patients did not have antecedent angina at baseline. When the SAQ-AF score was analyzed as a dichotomous variable, separating those with and without residual angina (ie, SAQ-AF score of 100 vs <100, respectively), the absolute difference in the proportion completely angina-free favored complete revascularization by 3.2%, a more notable difference. Thus for every 31 patients treated with a complete revascularization strategy, 1 additional patient would be expected to be angina-free 3 years later compared with a culprit lesion–only strategy.
The benefit of complete revascularization on freedom from angina appeared to be greater in those with tighter nonculprit lesions (visual ≥80% or quantitative coronary angiography ≥60% stenosis) where the absolute difference widened to 4.7% (a number needed to treat of 21). By contrast, in those with less severe nonculprit lesions, there did not appear to be any benefit of complete revascularization. This interaction with respect to stenosis severity on SAQ-AF score, a patient-reported outcome, was also observed on the primary clinical outcomes of the main COMPLETE trial.19 Given this finding, a physiology-guided strategy may further refine which nonculprit lesions benefit most from PCI. The recent FLOWER-MI trial, although not specifically powered for noninferiority, showed no difference between angiography-guided and fractional flow reserve–guided strategies, while reducing the number of nonculprit lesion PCI procedures in the fractional flow reserve group.20 Additional adequately powered large-scale trials comparing a physiology-guided complete revascularization strategy to an angiography-guided strategy are needed to establish noninferiority for efficacy and possible superiority for safety with a physiology-guided strategy by reducing the number of unnecessary nonculprit lesion PCI procedures.
Finally, when the results of our analysis are viewed in the context of total angina burden over the course of the trial, there was a more marked benefit of complete revascularization. These data provide additional important information for the patient and physician to consider in the context of shared decision-making, a process that is highlighted in current revascularization guidelines.7
Our trial has several limitations that warrant consideration. First, about 14% of health status measurements were missing at final follow-up. We performed sensitivity analyses, including multiple imputation (eTable 4 in Supplement 2) to account for missing data, and these analyses were consistent with the results of the primary analysis. Second, measurement of the SAQ occurred at only 3 time points. More interim assessments would have allowed for a more granular assessment of angina status in the intervening time periods. However, the fact that the benefit at 6 months was extended to 3 years is reassuring with respect to durability and clinical importance of the differences observed. Third, over the entire course of the trial, approximately 13% of patients crossed over from culprit lesion–only PCI to complete revascularization after experiencing an angina-related outcome event, which may have narrowed the difference in angina status at study end as measured by the SAQ. To capture the impact of these interim angina-related episodes, we evaluated total angina burden, which included not only residual angina at study end, but also any angina-associated events over the course of the trial, and this demonstrated a consistent benefit of complete revascularization. Fourth, the trial was open label and knowledge of treatment allocation may have affected how patients responded to the SAQ. However it is reassuring that the absolute difference in the proportion of angina-free patients observed at 6 months (where patient knowledge of treatment allocation would have been expected to have a greater impact) actually increased at 3-year follow-up.
In summary, in patients with STEMI and multivessel CAD, both complete and culprit lesion–only revascularization strategies improve angina-related quality of life, with a slightly greater proportion of patients being angina-free with complete revascularization. The modest benefit of complete revascularization on angina status appeared to be mainly observed in patients with more severe nonculprit lesion stenosis severity. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.
Accepted for Publication: July 25, 2022.
Published Online: September 21, 2022. doi:10.1001/jamacardio.2022.3032
Corresponding Author: Shamir R. Mehta, MD, MSc, Population Health Research Institute, David Braley Research Building, Hamilton General Hospital, 237 Barton St E, Hamilton, ON L8L 2X2, Canada (smehta@mcmaster.ca).
Author Contributions: Dr Mehta and Mr Wang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Mehta, Wang, Wood, Mehran, Storey, Steg, Sheth, Bainey, Jolly, Moreno, Cairns.
Acquisition, analysis, or interpretation of data: Mehta, Wang, Wood, Spertus, Cohen, Storey, Steg, Pinilla-Echeverri, Bainey, Bangalore, Cantor, Faxon, Feldman, Jolly, Kunadian, Lavi, Lopez-Sendon, Madan, Rao, Rodés-Cabau, Stankovic, Bangdiwala, Cairns.
Drafting of the manuscript: Mehta, Wang, Bainey.
Critical revision of the manuscript for important intellectual content: Wang, Wood, Spertus, Cohen, Mehran, Storey, Steg, Pinilla-Echeverri, Sheth, Bainey, Bangalore, Cantor, Faxon, Feldman, Jolly, Kunadian, Lavi, Lopez-Sendon, Madan, Moreno, Rao, Rodés-Cabau, Stankovic, Bangdiwala, Cairns.
Statistical analysis: Wang, Wood, Bangdiwala.
Obtained funding: Mehta.
Administrative, technical, or material support: Pinilla-Echeverri, Sheth, Feldman, Jolly, Lavi.
Supervision: Mehta, Storey, Pinilla-Echeverri, Jolly, Moreno.
Conflict of Interest Disclosures: Dr Mehta reported grants from AstraZeneca, Boston Scientific, and Canadian Institutes of Health Research during the conduct of the study and personal fees from Janssen Pharmaceuticals outside the submitted work. Dr Wood reported grants from Edwards Lifesciences, Abbott Vascular, and Medtronic outside the submitted work. Dr Spertus reported grants from Abbott Vascular and American College of Cardiology Foundation outside the submitted work; a patent for copyright to the Kansas City Cardiomyopathy Questionnaire and Peripheral Artery Questionnaire with royalties; grants from Abbott Vascular, Bristol Myers Squibb, and Janssen Pharmaceuticals; personal fees from Bayer, Bristol Myers Squibb, Novartis, Merck, Imbria Pharmaceuticals, Terumo, and United Healthcare; and is a member of the board of directors for Blue Cross Blue Shield of Kansas City outside the submitted work. Dr Cohen reported grants and personal fees from Abbott Vascular, Medtronic, Boston Scientific, and Svelte outside the submitted work. Dr Mehran reported grants from Beth Israel Deaconess, Biosensors, Biotronik, Bristol Myers Squibb, Boston Scientific, CallAegis, Concept Medical, CSL Behring, DSI, Duke University, Humacyte, Idorsa Pharmaceuticals, Insel Gruppe AG, Janssen, Medtronic, Novartis Research, OrbusNeich, Philips, Vivasure, and Zoll, all paid to the institution; grants from Abbott, Abiomed, Applied Therapeutics, Arena, AstraZeneca, Bayer, CardiaWave, CellAegis, CERC, Chiesi, and Transverse Medical; consulted for California Institute for Regenerative Medicine, Cine-Med Research, Janssen, and WebMD; served on the advisory boards of Abbott, Arena, Biotronik, CardiaWave, Chiesi, Concept Medical, Humacyte, Magenta, Novartis, and Philips, all paid to the research institution; served on the board of trustees for the American College of Cardiology (unpaid); served on the Women in Innovations Committee of SCAI; served as faculty for CRF (unpaid); <1% equity of Applied Therapeutics, Elixir Medical, STEL, and Claret Medical (Boston Scientific Corp divested final stock options); and other support from AM Pharma, Alleviant Medical, CeloNova BioSciences, Idorsia Pharmaceuticals, American Medical Association Scientific Advisory Board, and ControlRad outside the submitted work. Dr Storey reported personal fees from AstraZeneca, Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL Behring, GlyCardial Diagnostics, Hengrui, Idorsia, Novartis, PhaseBio, Cytosorbents, Sanofi Aventis, Thromboserin, Portola, Medscape, and Intas Pharmaceuticals and institutional research grants from AstraZeneca, GlyCardial Diagnostics, Cytosorbents, and Thromboserin outside the submitted work. Dr Steg reports grants and personal fees from Amarin, Bayer, Servier, and Sanofi; personal fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Idorsia, Novartis, Novo Nordisk, Pfizer, Sanofi/Lexicon, Myokardia, Regeneron, Phase Bio, and Merck; personal fees and nonfinancial support from AstraZeneca; and a patent on alirocumab for cardiovascular risk reduction, assigned to Sanofi, issued outside the submitted work. Dr Pinilla-Echeverri reports grants from Boston Scientific, AstraZeneca, Canadian Institutes of Health Research, and Health Research Institute during the conduct of the study and personal fees from Abbott Vascular, Conavi, Philips, Novartis, and Amgen outside the submitted work. Dr Sheth reported personal fees and grants from Abbott Vascular and Edwards Life Sciences outside the submitted work. Dr Bangalore reported grants from REATA and Abbott Vascular and personal fees from Abbott Vascular, Biotronik, Pfizer, Boston Scientific, and Amgen outside the submitted work. Dr Faxon reports participation on a data safety monitoring board or advisory board for Aegis-CSL112/C5Research-Cleveland Clinic, Agent/Boston Scientific, Apollo/Baim Institute, SMART/Baim Institute, Expand TVR/Baim Institute, and otsVADd/Otsuka and leadership or fiduciary role in other board, society, committee or advocacy group, unpaid for Alliance for a Healthy Generation. Dr Jolly reported grants from Boston Scientific and personal fees from Medtronic outside the submitted work. Dr Lopez-Sendon reported grants from Population Health Research Institute, McMaster University, and Hamilton Health Science during the conduct of the study; grants from Amgen, AstraZeneca, Pfizer, Bayer, Boehringer Ingelheim, and Merck outside the submitted work; and personal fees from Bayer and Menarini outside the submitted work. Dr Moreno reports other support from Abbott Vascular, Boston Scientific, Biosensors, Biotronik, Medtronic, Daiichi-Sankyo, Amgen, AstraZeneca, Edwards Lifesciences, Terumo, Philips, and Cardinal Health outside the submitted work. Dr Cairns reports grants from Boston Scientific, AstraZeneca, CIHR, and Edwards Laboratories during the conduct of the study and grants from AstraZeneca; nonfinancial support from Boston Scientific; and personal fees from Abbott, Bayer, and BMS Pfizer outside the submitted work. No other disclosures were reported.
Funding/Support: This study was supported by the Canadian Institute of Health Research with additional support from AstraZeneca and Boston Scientific.
Role of the Funder/Sponsor: Canadian Institutes of Health Research with additional support from AstraZeneca and Boston Scientific had no role in the design and conduct of the study.
Group Information: The COMPLETE Trial Investigators are listed in Supplement 3.
Data Sharing Statement: See Supplement 4.
1.Park
DW, Clare
RM, Schulte
PJ,
et al. Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction.
JAMA. 2014;312(19):2019-2027. doi:
10.1001/jama.2014.15095PubMedGoogle ScholarCrossref 3.Gershlick
AH, Khan
JN, Kelly
DJ,
et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial.
J Am Coll Cardiol. 2015;65(10):963-972. doi:
10.1016/j.jacc.2014.12.038PubMedGoogle ScholarCrossref 5.Engstrøm
T, Kelbæk
H, Helqvist
S,
et al; DANAMI-3—PRIMULTI Investigators. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.
Lancet. 2015;386(9994):665-671. doi:
10.1016/S0140-6736(15)60648-1PubMedGoogle ScholarCrossref 6.Mehta
SR, Wood
DA, Storey
RF,
et al; COMPLETE Trial Steering Committee and Investigators. Complete revascularization with multivessel PCI for myocardial infarction.
N Engl J Med. 2019;381(15):1411-1421. doi:
10.1056/NEJMoa1907775PubMedGoogle ScholarCrossref 7.Lawton
JS, Tamis-Holland
JE, Bangalore
S,
et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Circulation. 2022;145(3):e4-e17. doi:
10.1161/CIR.0000000000001039PubMedGoogle ScholarCrossref 8.Jang
JS, Spertus
JA, Arnold
SV,
et al. Impact of multivessel revascularization on health status outcomes in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease.
J Am Coll Cardiol. 2015;66(19):2104-2113. doi:
10.1016/j.jacc.2015.08.873PubMedGoogle ScholarCrossref 9.Ibrahim
H, Sharma
PK, Cohen
DJ,
et al. Multivessel versus culprit vessel-only percutaneous coronary intervention among patients with acute myocardial infarction: insights from the TRANSLATE-ACS observational study.
J Am Heart Assoc. 2017;6(10):e006343. doi:
10.1161/JAHA.117.006343PubMedGoogle ScholarCrossref 10.Mehta
SR, Wood
DA, Meeks
B,
et al; COMPLETE Trial Steering Committee and Investigators. Design and rationale of the COMPLETE trial: A randomized, comparative effectiveness study of complete versus culprit-only percutaneous coronary intervention to treat multivessel coronary artery disease in patients presenting with ST-segment elevation myocardial infarction.
Am Heart J. 2019;215:157-166. doi:
10.1016/j.ahj.2019.06.006PubMedGoogle ScholarCrossref 18.Al-Lamee
R, Howard
JP, Shun-Shin
MJ,
et al. Fractional flow reserve and instantaneous wave-free ratio as predictors of the placebo-controlled response to percutaneous coronary intervention in stable single-vessel coronary artery disease.
Circulation. 2018;138(17):1780-1792. doi:
10.1161/CIRCULATIONAHA.118.033801PubMedGoogle ScholarCrossref