Papering over the cracks: meta-analysis to define the role of percutaneous coronary intervention in patients with stable angina.

Canadian Journal of Cardiology 29 (2013) 411– 414 Editorial Papering Over the Cracks: Meta-analysis to Define the Role of Percutaneous Coronary Intervention in Patients With Stable Angina David D. Waters, MD Division of Cardiology, San Francisco General Hospital, and the Department of Medicine, University of California, San Francisco, San Francisco, California, USA See article by Thomas et al., pages 472-482 of this issue. “Our findings seem to indicate that summarizing all the informa- tion contained in a set of trials into a single odds ratio may greatly oversimplify an extremely complex issue. The popularity of meta- analysis may at least partly come from the fact that it makes life simpler and easier for reviewers as well as readers. However, over- simplification may lead to inappropriate conclusions. 1 ” In this issue of the Canadian Journal of Cardiology, a meta- analysis by Thomas et al. compares percutaneous coronary in- tervention (PCI) with medical therapy in patients with stable angina. 2 The authors include 10 randomized trials involving 6752 patients, and conclude that PCI was not associated with better angina relief, or reductions in all-cause or cardiovascular mortality, or myocardial infarction. They state that their find- ings “reinforce existing clinical practice guidelines that the ini- tial approach to patients with stable angina should be medical therapy.” Other recent meta-analyses have addressed this topic, 3-6 and 2 of them came to similar conclusions as these authors. 3,6 However, Schomig et al. concluded that PCI reduced total and cardiovascular mortality compared with medical therapy, 4 and Wijeysundera et al. concluded that PCI provided better angina relief with no advantage for other end points. 5 Why this divergence? Meta-analyses usually present a straightforward conclusion, leaving the messy details buried within the body of the report. In this instance, the results of a meta-analysis crucially depend upon the studies that are in- cluded. Do we wish to restrict our analysis to patients with stable angina, or should we include trials of patients with silent ischemia or survivors early after myocardial infarction? Perhaps we should dig deeper, to try to understand the factors that contribute to the results of the trials included, or not included, in these meta-analyses. Received for publication July 10, 2012. Accepted July 10, 2012. Corresponding author: Dr David D. Waters, Division of Cardiology, Room 5G1, San Francisco General Hospital, 1001 Potrero Avenue, San Fran- cisco, California 94114, USA. Tel.: ⫹1-415-206-8320. E-mail: dwaters@medsfgh.ucsf.edu See page 413 for disclosure information. Improvements in PCI and Medical Treatment The treatments being compared, PCI and medical therapy, have both improved greatly over the time period when these trials were conducted. For example, men with single or double vessel disease were enrolled into the Angioplasty Compared to Medicine (ACME) study between 1987 and 1990. 7,8 Among the 100 angioplasties for single vessel disease, only 80 were successful, with success defined as a ⬎ 20% decrease in stenosis severity without periprocedural infarction or the need for ur- gent bypass surgery. 7 Within 6 months, 16 patients required 18 additional procedures for restenosis and 5 others underwent coronary bypass surgery. Medical therapy consisted of aspirin in almost all patients, calcium channel blockers in approxi- mately 3 quarters, and ␤ -blockers in approximately half. Early trials contribute disproportionately to the end points; for example, ACME contributed only 4.9% of the patients to the meta-analysis of Thomas et al., but 7.5% of the end point events. ACME was a perfectly acceptable trial for its era, but its results are not relevant to current practice. The fact that the results of ACME are within the range of the results of other trials is more than likely coincidental. The second Randomized Intervention Treatment of An- gina 2 (RITA-2) contributed 1018 of the 6757 patients in the meta-analysis; however, only 9% of the RITA-2 patients ran- domized to PCI received stents, and only 13% of all RITA-2 patients were receiving a lipid-lowering drug at baseline. 9 Al- though incremental advances have occurred in both technical and periprocedural aspects of PCI, and in medical therapy, the quantum leaps have been stents and statins respectively. Trials lacking stents and statins are archaic and do not apply to con- temporary practice. The Optimal Medical Therapy of COURAGE Medical therapy was not the primary focus of the early trials comparing PCI with medical therapy. The aim of medical treatment in these trials was primarily angina prevention using nitrates, ␤ -blockers, and calcium channel blockers. The Clin- ical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was different. COUR- 0828-282X/$ – see front matter © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2012.07.009