Editors’ pickHealth

Complete Revascularization Linked to Better LT NSTEMI Survival

Complete rather than culprit-only revascularization appears to pay off long-term for patients with multivessel disease presenting with non-ST-segment elevation MI (NSTEMI), suggests an observational cohort study.

After nearly 5 years follow-up, single-stage complete revascularization at the time of initial percutaneous coronary intervention (PCI) was associated with a 10% relative reduction in mortality risk after adjustment (hazard ratio [HR], 0.89; 95% CI, 0.76 – 0.98), despite an initial higher risk of in-hospital mortality.

“This suggests that the short-term investment in complete revascularization is worth it in the long-term, a similar adage to [coronary artery bypass grafting] CABG,” senior author Daniel Jones, MD, PhD, Barts Health NHS Trust, London, told theheart.org | Medscape Cardiology in an email.

The issue of complete versus culprit-only vessel intervention during PCI for acute coronary syndrome has been debated for years, with it generally now accepted that for STEMI, complete revascularization at the time of the index PCI is beneficial. However, there is a paucity of data regarding the optimal approach toward nonculprit lesion revascularization for NSTEMI, he noted.

“This is surprising because NSTEMI cohort comprises the majority of patients with MI, often with greater complexity and incidence of multivessel disease,” Jones said. “This study adds important evidence to this debate suggesting that in NSTEMI, complete revascularization is associated with improved outcomes.”

“Although crucially this should still be considered hypothesis-generating, with a prospective randomized trial necessary to confirm these findings.”

Reached for comment, Deepak Bhatt, MD, Brigham & Women’s Hospital, Boston, said that only a randomized trial can say if there’s a mortality reduction with complete revascularization but that the observed association is solid.

“They looked at the patients and there is lower mortality; there’s no getting around that fact,” he said. “The only question is: Is that lower mortality a result of the complete revascularization or is it just that some characteristics of the patients who got complete revascularization were just also associated with better mortality, or is it some combination of those two factors, which is most often the case in observational analyses.”

On the other hand, Bhatt pointed out that patients who underwent complete vs culprit-only revascularization were older and more likely to be diabetic and to have had a prior heart attack.

“So in fact, you would think those things would predict higher mortality, so that works in the authors’ favor,” he said.

The study was published in the October 23 issue of the Journal of the American College of Cardiology.

Early Risks Fade by 6 Months

The investigators led by Krishnaraj Rathod, MD, also with Barts Health NHS Trust, examined data from 21,857 patients with NSTEMI who underwent PCI between January 2005 and May 2015 at eight MI centers in London.

Their mean age was 67.3 years, 74% were men, and 58% had hypertension. Procedural success rates were similar between the complete revascularization (n = 11,737) and culprit-only (n = 10,120) groups.

The complete revascularization group had a higher rate of in-hospital death than the culprit-only group (2.3% vs 1.5%; P = .002) but a lower rate of repeat PCI (0.6% vs 1.0%; P = .015). This likely explains why major adverse cardiac event rates were similar in the two groups (4.1% vs 3.8%; P = .462), although arterial complications were more common with complete revascularization (0.6% vs 0.4%; P = .008)

After a median follow-up of 4.6 years, the mortality rate was 22.5% in the complete revascularization group and 25.9% in the culprit-only group (= .0005).

This benefit was observed after 6 months and is supported by a landmark analysis, showing patients undergoing complete revascularization (CR) had significantly reduced rates of all-cause mortality from 6 months out to 5 years (HR, 0.65; 95% CI, 0.35 – 0.82; P = .0005).

“A recent meta-analyses of all the studies in STEMI does suggest a mortality benefit similar to what we have seen suggested by this observational data,” Jones said. “Therefore, I would argue that the results in this large NSTEMI cohort are as expected and consistent with the data for STEMI. Cardiogenic shock is a different beast, with the results difficult to explain and really only based on one RCT.”

The present analysis is the largest study to date examining long-term outcomes between the two strategies in NSTEMI, but the authors note that “An important difference exists in angiographic findings in STEMI and NSTEMI with respect to determining the culprit artery,” which tends to be obvious in STEMI but is not always possible in NSTEMI.

“There are now emerging data to support fractional flow reserve-guided nonculprit intervention in this patient cohort but this isn’t something we assessed as a part of this study and would be an important confounder,” Jones said.

He noted that future randomized controlled trials (RCTs) would have to include this in the protocol and that their group recently published data on the benefits of using optical coherence tomography in identifying unclear culprit vessels and optimizing PCI outcomes.

Unanswered Questions

In an accompanying editorial, Ehtisham Mahmud, MD, University of California San Diego Sulpizio Cardiovascular Center, La Jolla, and Ori Ben-Yuhuda, MD, Cardiovascular Research Foundation, New York City, write that the study has several strengths.

“Lesions with less than 75% angiographic stenosis were required to define the presence of multivessel CAD, thereby identifying hemodynamically significant CAD, a superior definition to the 50% dichotomous cut point used in many prior studies,” they say. “The landmark analysis at 6 months demonstrating a 35% reduction in longer-term mortality for the CR group is an additional important contribution of this study, because it justifies the slightly higher short-term in-hospital risk of CR.”

Nevertheless, Mahmud and Ben-Yuhuda agree that a randomized trial is needed to confirm the results, citing a number of unanswered questions. They include whether CR should be performed during a single session or staged; the optimal window for revascularization; the role of physiological assessment of disease severity; which subgroups benefit most from CR; and whether systematic risk stratification after revascularization would alter the findings.

“Two decades after the TIMI-18 trial showed that an early invasive approach with revascularization was superior to a conservative approach in ACS, we are finally moving to an era in which we will address the equally important question of the optimal revascularization approach,” the editorialists conclude.

“Although physician judgment will always play a paramount role in ensuring patient safety and optimal patient selection for CR during NSTEMI, completing the job of multivessel PCI where feasible appears justified.”

Jones, Mahmud, and Ben-Yuhuda report no relevant conflicts of interest. Bhatt reports grant support/research contracts with Abbott Vascular, AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly, Medtronic, Sanofi-Aventis, The Medicines Company, and Chiesi.

J Am Coll Cardiol. 2018;72:1989-1999 and 2000-2002. Abstract, Editorial

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