December 3rd, 2013
Stents Lose in Comparisons with Surgery and Medical Therapy
Despite the enormous increase in the use of stents in recent decades, there is little or no good evidence comparing their use to the alternatives of CABG surgery or optimal medical therapy in patients also eligible for these strategies. Now two meta-analyses published in JAMA Internal Medicine provide new evidence that the alternatives to PCI remain attractive and that some of the growth in PCI may have been unwarranted.
In the first paper, Ilke Sipahi and colleagues performed a meta-analysis of trials in the modern era that compared PCI and CABG in patients with multivessel disease. They identified six randomized trials, including more than 6000 patients, in which, to reflect contemporary practice, at least one arterial graft was used in the CABG arm and at least 70% of patients received stents in the PCI arm. By themselves, these trials were not powered to detect differences in mortality and other major individual outcomes.
With an average 4.1 years of follow-up, CABG was associated with significant reductions in total mortality, myocardial infarction, repeat revascularization, and the rate of major adverse cardiovascular and cerebrovascular events (MACCE). CABG was also associated with a trend for excess strokes. Here are the risk ratios for CABG:
- Mortality: 0.73, CI 0.62-0.86, p<0.001
- MI: 0.58, CI 0.48-0.72, p<0.001
- Repeat revascularization: 0.29, CI 0.21-0.41, p<0.001
- MACCE: 0.61, CI 0.54-0.68, p<0.001
- Stroke: 1.36, CI 0.99-1.86, p=0.06
Results remained consistent when the investigators looked both at trials that were limited to diabetics and at trials that were not. A similar analysis found no difference in trials using bare-metal stents or drug-eluting stents.
The authors conclude that “CABG should be the preferred revascularization method for most patients with multivessel coronary artery disease.”
In the second paper, Kathleen Stergiopoulos and colleagues analyzed studies that compared PCI plus medical therapy with medical therapy alone in more than 4000 patients with stable coronary artery disease and documented ischemia. With a median 5 years’ follow-up, there were no significant differences in death, nonfatal MI, unplanned revascularization, or angina. Here are the odds ratios for PCI plus medical therapy:
- Mortality: 0.90, CI 0.71-1.16, p=0.42
- Nonfatal MI: 1.24, CI 0.99-1.56, p=0.06
- Unplanned revascularization: 0.64, CI 0.35-1.17, p=0.14
- Angina: 0.91, CI, 0.57-1.44, p=0.67
The results, write the authors, have important implications regarding our understanding of the relationship between ischemia and clinical outcomes. The findings “suggest that myocardial ischemia may be more of a marker for atherosclerotic burden” and that “the relationship between ischemia and mortality is not altered or ameliorated” by a stent in a blocked artery. Stents don’t prevent future clinical events because these are most often due to “new plaque ruptures in distant coronary segments without flow-limiting stenoses.”
“Finally,” the authors write, “these findings call into question the common practice of ischemia-guided revascularization (either using noninvasive testing techniques or FFR) where the presence of myocardial ischemia routinely determines patient selection for coronary angiography and revascularization.” Here is their summary of the situation:
Thus, the lesions that are responsible for most cases of MI and subsequent death are not severe enough to induce ischemia on stress testing, and the lesions responsible for causing ischemia do not tend to rupture. Since intervening on a marker of an outcome that is not in the causal pathway of the subsequent adverse clinical events would not be expected to reduce those events, it should not be surprising that prior clinical trials and meta-analyses consistently demonstrate that PCI fails to reduce death or MI in patients with stable CAD who are concomitantly aggressively treated with contemporary medical therapy for secondary prevention.
Unfortunately, according to the authors, although there are no data to support it, “this ischemia-driven approach to PCI is a cornerstone of daily practice in the evaluation of patients with chest pain or known CAD—endorsed by the American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines.”