COMPLETE Trial - Cardionerds Journal Club

CardioNerds Journal Club is a monthly forum for Cardionerds to discuss and breakdown recent publications on twitter and are produced with a corresponding infographic and detailed blog post. For more information, check out the CardioNerds Journal Club Page. This Journal Club focuses on the COMPLETE Trial.

Table of contents for the COMPLETE Trial summary:

Visual abstract
Summary
References
Credits
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COMPLETE Trial Visual Abstract — COMPLETE Trial Summary Visual Abstract

October 10, 2019

Complete Revascularization with Multivessel PCI for Myocardial Infarction

The COMPLETE Trial

Shamir R. Mehta, M.D., David A. Wood, M.D., Robert F. Storey, M.D., Roxana Mehran, M.D., Kevin R. Bainey, M.D., Helen Nguyen, B.Sc., Brandi Meeks, M.Sc., Giuseppe Di Pasquale, M.D., Jose López-Sendón, M.D., David P. Faxon, M.D., Laura Mauri, M.D., Sunil V. Rao, M.D., Laurent Feldman, M.D., P. Gabriel Steg, M.D., Álvaro Avezum, M.D., Tej Sheth, M.D., Natalia Pinilla-Echeverri, M.D., Raul Moreno, M.D., Gianluca Campo, M.D., Benjamin Wrigley, M.D., Sasko Kedev, M.D., Andrew Sutton, M.D., Richard Oliver, M.D., Josep Rodés-Cabau, M.D., Goran Stanković, M.D., Robert Welsh, M.D., Shahar Lavi, M.D., Warren J. Cantor, M.D., Jia Wang, M.Sc., Juliet Nakamya, Ph.D., Shrikant I. Bangdiwala, Ph.D., and John A. Cairns, M.D. for the COMPLETE Trial Steering Committee and Investigators.

Link to article

Primary percutaneous coronary intervention (PCI) is the reperfusion therapy of choice for patients with ST-segment elevation myocardial infarction (STEMI), and several of these patients are found to have multivessel disease at the time of PCI. The optimal treatment of non-culprit lesions, whether by medical treatment only or revascularization, is debatable.
Staged non-culprit lesion PCI was associated with lower cardiovascular mortality in observational studies^1,2, as well as in meta-analyses.^3-5
Randomized control trials have shown that complete revascularization (Primary PCI + non-culprit PCI) mainly reduced the risk of subsequent revascularization.^6-9

Table 1. Previous randomized controlled trials assessing the outcomes of complete revascularization versus primary PCI of the culprit lesion only in patients with STEMI and multivessel disease.

Relevant Guidelines for the COMPLETE Trial

The 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization recommend routine revascularization of non-infarct-related artery lesions in STEMI patients with multivessel disease (Class IIa recommendation).¹⁰
The 2015 ACC/AHA Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction recommends the consideration of PCI of a non-infarct artery in selected patients with STEMI and multivessel disease who are hemodynamically stable (Class IIb recommendation).¹¹

Study Rational

Previous individual randomized control trials lacked the power to determine if non-culprit PCI in patients with STEMI and multivessel disease would lead to a reduction in the risk of cardiovascular death or new myocardial infarction.

Objective

To determine if PCI of angiographically significant non-culprit lesions in patients with STEMI and multivessel disease would lead to a significant reduction in cardiovascular death, myocardial infarction, or ischemia-driven revascularization.

COMPLETE Trial:
Randomized, blinding to trial center (otherwise open-label), International (140 centers, 31 countries, N = 4041), Enrollment February 2013 to march 2017, Follow up: Mean 36.2 months; median 35.8 months (interquartile range, 27.6 to 44.3)

Intervention
Patients with STEMI and multivessel CAD who had undergone successful culprit-lesion PCI were assigned to either complete revascularization with PCI of angiographic significant non culprit lesions + medical therapy (N=2016) or no further revascularization (N=2025) and treated with medical therapy alone (DAPT with aspirin and ticagrelor ((60mg BID)) for at least 1 year, statin, ACEI/ARB, MRA, and BB were recommended).

Enrollment criteria

COMPLETE Trial: Inclusion and Exclusion Criteria

Outcomes

Statistical Analysis
Intention-to-treat analysis, coprimary outcomes analyzed with time to first event approach, estimates of hazard ratios and 95% CI were calculated with cox proportional hazards models; the two treatment groups were compared with stratified log rank test; cumulative incidence estimated with kaplan-meier method

Notable Baseline Characteristics (Complete Revascularization vs Culprit-Lesion-only):

Average Age: 61.6 vs 62.4
Male Sex: 80.5% vs 79.1%
Medical history (Complete Revascularization only)
- Hypertension: 48.7%
- Diabetes mellitus: 19.1%
- Dyslipidemia: 37.9%
- Previous MI: 7.3%
- Previous PCI: 7.0%
- Previous stroke: 3.2%
- Chronic renal insufficiency: 2.0%
Medications at discharge (Complete Revascularization only)
- Aspirin: 99.8%
- P2Y12 inhibitor
  - Any: 99.4%
  - Ticagrelor: 64.4%
  - Prasugrel: 9.6%
  - Clopidogrel 25.6%
- Beta-blocker: 88.1%
- ACEi/ARB: 85.5%
- ARB: 33%
- Calcium antagonist: 26%
- Statin: 98.2%
Syntax Score
- Culprit lesion specific: 8.8 vs 8.6
- Non Culprit lesion specific score 4.6 vs 4.6
Location of culprit lesion
- Left main 0.2 vs 0.2%
- Left anterior descending 34.4 vs 33.9%
- Circumflex 18.0 vs 15.8%
- Right coronary 47.4 vs 50.1%

Primary and Secondary Outcomes

Adverse events

COMPLETE Trial Conclusions

Among patients with STEMI and multivessel coronary artery disease, complete revascularization with non-culprit lesion PCI performed during index hospitalization or soon after discharge is superior to culprit-lesion only PCI in reducing risk of cardiovascular death, myocardial infarction as well as reducing risk of cardiovascular death, myocardial infarction, and ischemia-driven revascularization.

Limitations & Considerations

Non-culprit lesion PCI was not performed during the index culprit lesion PCI for STEMI
No patients with cardiogenic shock were enrolled in the trial and thus these results cannot be extrapolated to such patients
Cross-over to non-culprit PCI occurred in 4.7% of the culprit lesion only PCI group; unclear if the results would be similar if complete revascularization was observed in fewer patients or crossover criteria was more liberal to include more patients
There weren’t as many women as there were men in this study; race and ethnicity was not evaluated as well
Different stents were used
178 of the 2016 from the complete revascularization group had more than one non-culprit lesion
Non-culprit lesions had relatively low SYNTAX score

1. Hannan EL, Samadashvili Z, Walford G, et al. Culprit vessel percutaneous coronary intervention versus multivessel and staged percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel disease. JACC Cardiovasc Interv 2010;3:22-31.

2. Bainey KR, Mehta SR, Lai T, Welsh RC. Complete vs culprit-only revascularization for patients with multivessel disease undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review and meta-analysis. American heart journal 2014;167:1-14.e2.

3. Bainey KR, Welsh RC, Toklu B, Bangalore S. Complete vs Culprit-Only Percutaneous Coronary Intervention in STEMI With Multivessel Disease: A Meta-analysis and Trial Sequential Analysis of Randomized Trials. Can J Cardiol 2016;32:1542-51.

4. Elgendy IY, Mahmoud AN, Kumbhani DJ, Bhatt DL, Bavry AA. Complete or Culprit-Only Revascularization for Patients With Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Pairwise and Network Meta-Analysis of Randomized Trials. JACC Cardiovasc Interv 2017;10:315-24.

5. Tarantini G, D’Amico G, Brener SJ, et al. Survival After Varying Revascularization Strategies in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Artery Disease: A Pairwise and Network Meta-Analysis. JACC Cardiovasc Interv 2016;9:1765-76.

6. Wald DS, Morris JK, Wald NJ, et al. Randomized trial of preventive angioplasty in myocardial infarction. The New England journal of medicine 2013;369:1115-23.

7. 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. Journal of the American College of Cardiology 2015;65:963-72.

8. Engstrøm T, Kelbæk H, Helqvist S, et al. 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 (London, England) 2015;386:665-71.

9. Smits PC, Laforgia PL, Abdel-Wahab M, et al. Fractional flow reserve-guided multivessel angioplasty in myocardial infarction: three-year follow-up with cost benefit analysis of the Compare-Acute trial. EuroIntervention 2020;16:225-32.

10. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. European heart journal 2019;40:87-165.