To stent or not to stent ? Meta-analysis challenges the results of ISCHEMIA trial, EuroPCR 2021.
The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. Revisiting this question once again that was thought by many to have been settled by results of ISCHEMIA trial last year, a new meta-analysis suggests that patients with stable coronary artery disease (SCAD) undergoing elective revascularization are at a lower risk of dying from cardiac causes over the long term when compared with patients treated with medical therapy alone.
The findings were presented this week as a late-breaking clinical trial at EuroPCR 2021, and simultaneously published in the European Heart Journal. In this analysis, the benefit appeared directly related to the duration of follow-up, with investigators reporting that the longer the follow-up, the lower the risk of cardiac death and spontaneous MI among those who underwent PCI or CABG surgery.
Twenty-five trials involving 19 806 patients (10 023 randomised to revascularisation plus medical therapy and 9783 to medical therapy alone) were included. These include some well-known trials like MASS-1, RITA-2, COURAGE, ORBITA, FAME 2, and ISCHEMIA.
Treatment effects were measured by rate ratios (RRs) with 95% confidence intervals, using random-effects models. Cardiac mortality was the pre-specified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI, and stroke. Longest follow-up data were abstracted.
Researchers observed the following trends:
1. A 21% lower risk of cardiac mortality among patients who underwent coronary revascularization compared with medical therapy alone.
2. Risk of spontaneous MI reduced by 26% with revascularisation .
3. For each 4-year increase in follow-up, the risk of dying from cardiac causes declined significantly by 19% with allocation to revascularization versus medical therapy alone.
4. All-cause mortality, any MI, and stroke risk did not differ significantly between strategies.
Does this really contradict ISCHEMIA findings?
Chief author Nevarese suggests that the results actually comply with ISCHEMIA findings. The difference is
Firstly, the primary endpoint: in ISCHEMIA it was all cause mortality, and in this meta-anlysis it was Cardiac specific deaths.
Second, longer mean follow-up duration of this meta-analysis.
It is notable that there was crossing of the MI event curves in ISCHEMIA at longer follow-up hinting at a potential longer-term benefit to revascularization. While there was no significant difference in the risk of MI between the two strategies at 4 years, the invasive strategy was associated with a higher risk of MI early while there were more MIs with the conservative strategy in longer follow-up.
Navarese added, time since randomization appeared to make a difference. "For each 4-year increase in follow-up, the risk of dying from cardiac causes declined significantly by 19% with allocation to revascularization versus medical therapy alone." The mean follow-up in ISCHEMIA trial was only 3.2 years and this might be the reason that benefits of revascularisation could not obtain a significant value over medical therapy alone.
The ISCHEMIA trial investigators have announced plans to study patients for an additional 5 years beyond the original trial. As part of the ISCHEMIA-EXTEND study, which now includes more than 5,000 participants enrolled in the follow-up study, investigators say they plan to assess all-cause mortality "to provide patients and clinicians with robust evidence regarding survival following the two initial management strategies over the long term (~ 10 years)," according to the ISCHEMIA trial website.
To summarise, the present large-scale analysis of randomised trials shows a significant and consistent reduction of cardiac mortality in favour of elective coronary revascularisation plus medical therapy compared with medical therapy alone in stable coronary artery disease patients, the magnitude of which is directly associated with duration of follow-up and a lower risk of spontaneous MI. Lower cardiac mortality with revascularisation plus medical therapy was confirmed in all sensitivity analyses performed.
Source: European Heart Journal: Navarese EP, Lansky AJ, Kereiakes DJ, et al. Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis. Eur Heart J. 2021.