By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: Data from the CvLPRIT trial of complete vs. culprit-only percutaneous coronary intervention in ST-segment elevation myocardial infarction (MI) show a significantly lower rate of major adverse cardiovascular events, all-cause mortality, and lower composite MI in the complete revascularization group at a median follow-up of 5.6 years.
SOURCE: Gershlick AH, Banning AS, Parker E, et al. Long-term follow-up of complete versus lesion-only revascularization in STEMI and multivessel disease: The CvLPRIT Trial. J Am Coll Cardiol 2019;74:3083-3094.
In recent years, investigators have published several randomized trials concerning culprit-only percutaneous coronary intervention (PCI) vs. complete revascularization (CR) in ST-segment elevation myocardial infarction (STEMI). After Complete versus Culprit-Only Revascularization Strategies to treat Multivessel Disease after early PCI for STEMI (COMPLETE), a trial that included more than 4,000 patients, it is difficult at first to know what significance to attribute to the Complete versus Lesion-only Primary PCI Trial (CvLPRIT).
CvLPRIT creators randomized patients with STEMI and multivessel disease to CR or infarct-related, artery-only (IRA) PCI. CR was completed during the index procedure or prior to hospital discharge. The original CvLPRIT publication reported results at 12 months, with the primary endpoint a composite of all-cause death, recurrent MI, heart failure, and ischemia-driven revascularization. In the recent publication, long-term follow-up data were complete for 91.8% of the CR group and 92% of the IRA group.
At a median follow-up of 5.6 years, the composite major adverse cardiovascular event (MACE) rate was significantly lower in the CR group vs. IRA group (24% vs. 37.7%; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37-0.87; P = 0.0079). Although the trial was not powered for individual endpoints, the secondary composite endpoint of death or MI also favored CR, occurring in 10% of the CR group vs. 18.5% of the IRA group (HR, 0.47; 95% CI, 0.25-0.89; P = 0.0175).
In a landmark analysis from the 12-month time point to the end of follow-up, there was a trend toward a lower composite event rate in the CR group, but this did not meet statistical significance. The authors concluded the significantly lower rate of MACE in STEMI previously seen at one year in patients undergoing CR vs. culprit lesion-only PCI is sustained at long-term follow-up to a median of 5.6 years. At the longer-term follow-up, the composite of death and MI also was significantly lower among CR patients, with a relative risk reduction of nearly 50%.
There were some shortcomings associated with this investigation. CvLPRIT was not large. The authors of the original trial recruited only 296 patients, with 150 randomized to PCI of all angiographically significant lesions and 146 randomized to IRA PCI.
Investigators did not use hemodynamic tests of lesion significance (fractional flow reserve [FFR] or instantaneous wave-free ratio), which in other contexts have led to improved outcomes. Instead, the authors relied on angiographic definitions of significance only (lesion estimates of greater than 70% or 50% in two orthogonal views), which would be predicted to lead to overtreatment compared with an FFR-based approach. Finally, cardiovascular events in this trial were not adjudicated, but rather relied on site-level reporting. In the wake of the recent controversy over the EXCEL trial, it is important to recognize that even different definitions of MI as an endpoint can affect the overall results significantly.
In trials like CvLPRIT, the fact that a central clinical events committee did not adjudicate the occurrence of endpoints such as MI could lead to incorrect conclusions. Still, there were strengths. In addition to confirming a sustained effect of complete revascularization on MACE over time, longer-term results were positive (where the original 12-month report was not) in terms of the hard outcomes of death and MI. When added to the positive results of other trials, this provides compelling evidence for a benefit of CR in patients presenting with STEMI.
These results also are a reminder that patients presenting with acute coronary syndromes are fundamentally different than those with stable angina and demand a different approach. In the wake of the ISCHEMIA trial, this point is worth discussion with both patients and medical providers alike.
Nonetheless, take each case on an individual basis. For each patient, ask what achieving CR will require in terms of risks. Is the nonculprit PCI straightforward or a complex chronic total occlusion? Is the patient frail? Did he or she present with advanced chronic kidney disease or poor vascular access? Complete revascularization following STEMI should be considered in every case, but a patient-centered approach is required. Going forward, expect other investigators to elucidate the remaining uncertainties in this space, including the most optimal timing of additional revascularization.