September 3, 2019 — “Complete revascularisation is likely to prevent many thousands of recurrent heart attacks on a global basis every year compared with culprit-lesion-only percutaneous coronary intervention (PCI).” So says Professor Shamir R. Mehta (Population Health Research Institute, Hamilton, Ontario, Canada), who gave a Hot Line presentation of the COMPLETE trial results, which will be published simultaneously in the New England Journal of Medicine.1
“How to best manage the non-culprit lesions in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease has been a dilemma for some time,” explains Prof. Mehta. “While there have been some well-conducted randomised clinical trials of routine non-culprit lesion PCI, none have been powered to determine whether non-culprit PCI prevents hard endpoints such as cardiovascular (CV) death or myocardial infarction (MI).”
The large multinational COMPLETE trial was a comparative-effectiveness study that was powered to determine whether routine angiographically-guided PCI of significant non-culprit lesions, performed as a staged procedure, would prevent CV death or MI, compared with optimum guideline-directed medical therapy alone. “By concentrating on hard clinical endpoints, the study minimised the possible bias associated with the open-label design and focus on revascularisation as the sole endpoint driving possible benefit,” says Prof. Mehta. “We also wanted to look at the optimal timing of revascularisation, because there are conflicting data from prior trials about this. So patients were stratified according to whether PCI was to be conducted during the index hospitalisation or at a later date.”
The trial involved 4,041 patients from 140 centres in 31 countries who had undergone PCI of the culprit lesion. All coronary angiograms were evaluated in a central angiographic laboratory for lesion complexity, SYNTAX score, complications and results of PCI. The first co-primary outcome was a composite of CV death or MI, with the second co-primary endpoint including an additional element of ischaemia-driven revascularisation.Complete revascularisation led to a 26% reduction in the risk of CV death or MI and a 49% reduction in the risk of CV death, MI or ischaemia-driven revascularisation.
At a median follow-up of 3 years, the benefits of complete revascularisation over culprit-only PCI were highly significant for both co-primary outcomes: the rate of CV death or MI (7.8% vs 10.5%; hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60–0.91; p=0.004) and the rate of CV death, MI or ischaemia-driven revascularisation (8.9% vs 16.7%; HR 0.51; 95% CI 0.43–0.61; p<0.001). “Results were driven largely by a reduction in new MI, mainly type 1 (spontaneous) MI,” says Prof. Mehta.
In terms of safety, there was no significant difference between treatments in any of the safety outcomes, including stroke (p=0.27) and major bleeding (p=0.15). Overall contrast-induced nephropathy was not different between the groups, but there was a small excess in those receiving early non-culprit lesion PCI.
The impact of the timing of non-culprit lesion PCI on outcomes has important clinical implications. “We found that the benefit of complete revascularisation was similar when non-culprit PCI was conducted early—at a median of one day during the index hospitalisation (HR 0.77; 95% CI 0.59–1.00)—or when it was performed several weeks after hospital discharge (HR 0.69; 95% CI 0.49–0.97),” says Prof. Mehta. “The reason for this is probably because the benefit of complete revascularisation, at least on CV death or MI, seems to emerge over the long term. Most early events after STEMI are likely due to the underlying severity of the index infarction itself, rather than the non-culprit lesion.”
The COMPLETE trial is the first randomised trial to show the benefits of complete revascularisation, involving culprit and non-culprit lesions, on hard CV outcomes in patients with STEMI and multivessel disease. “Our data confirm what has been suggested in previous trials, that this strategy leads to a clinical benefit for these patients,” says Prof. Mehta. “In our trial, a patient’s risk of having another heart attack was cut by about one-quarter. That degree of benefit usually leads to a change in clinical practice.”
1. Mehta SR, et al. N Engl J Med 2019. doi/10.1056/NEJMoa1907775