Best Medical Therapy vs Revascularization for Stable Angina: The Beat Goes on!
Abstract & Commentary
By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque; Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.
Source: Schomig A, et al. Meta-analysis of 17 randomized trials of a percutaneous coronary intervention-based strategy in patients with stable coronary artery disease. J Am Coll Cardiol. 2008;52:894-904.
A long-standing controversy exists regarding use of angioplasty (PCI) vs best or optimal medical therapy in subjects with stable coronary disease (CAD). The recent COURAGE trial has spurred an increased interest in this issue, as comparable survival and MI outcomes with PCI or bypass surgery were found with optimal medical therapy (OMT) alone vs PCI and OMT. The TIME trial comparing medical vs PCI in the elderly (> 75) reported similar outcomes at one year, but more adverse outcomes at six months (Pfisterer M, et al. JAMA. 2003; 289:1117-1123). This report from Munich, Germany, is a meta-analysis of 17 trials of PCI with OMT compared to OMT alone. The purpose of the meta-analysis is "to evaluate whether PCI affects long-term prognosis in patients with stable CAD." Eligible subjects had stable CAD; patients with ACS were excluded. All trials reviewed were prospective and randomized. Trial dates ranged from 1993 to 2007, including COURAGE. Baseline characteristics between the two cohorts were equivalent. Extensive statistical tests were used in this analysis. The primary end point was all-cause death, death due to cardiac causes, or myocardial infarction. A total of 17 randomized trials consisting of 7,513 subjects, average age 60; 82% were male; half had a prior MI. Ninety-two percent of the invasive group underwent revascularization (drug eluting stents rarely). Twenty-eight percent of subjects assigned to medical treatment crossed over to revascularization over the average 51 months of the study.
Results: Subjects in the PCI group enjoyed a 20% reduction in the odds ratio of all-cause death. Superiority of PCI over medical therapy was found in 14 trials. PCI was associated with a 26% reduction in the odds ratio for all-cardiac death. Overall, during an average 51-month follow-up, PCI patients had a benefit, with a 20% decrease in the odds ratio of events compared to the medical treatment only strategy. Stents were used in < 50% of subjects, almost all non-drug eluting. Schomig et al emphasize that this study "constitutes a consistent and comprehensive investigation of available evidence by meta-analytical methodology. They emphasize that the meta-analytic approach worked well "with a substantial reduction of long-term mortality by this strategy."
PCI was considerably more advantageous in patients with a recent prior MI. A 20% reduction in odds ratio of death was noted in multiple analyses of the database. Twenty-eight percent of the OMT-alone patients received a non-protocol revascularization over long-term follow-up.
Schomig et al conclude, "There is little doubt that PCI relieves ischemia and improves exercise capacity of patients with angina pectoris." They underscore the fact that a substantial reduction of events was seen over an average of 51 months in the PCI cohort; they suggest that PCI resulted in a greater decrease of risk of non-fatal MI "because of improvement in technique." Schomig et al posit that in prior large MI patients, PCI is particularly beneficial. They "suggest that a PCI-based invasive strategy may improve long-term survival compared with a medical treatment-only strategy in patients with stable CAD; they call for a new large clinical trial powered for evaluating the impact of PCI on long-term mortality.
This extensive meta-analysis addresses almost 15 years of reports in the literature assessing the controversial subject of routine PCI or bypass surgery in patients with stable angina and CAD, as opposed to a strategy of medical therapy alone. The somewhat surprising finding of the meta-analysis is that there was a 20% reduction in fatal events in revascularized patients compared to OMT. Furthermore, 28% of OMT subjects ultimately had a non-protocol revascularization in the follow-up period of 51 months.
The lack of increased risk of adverse outcomes in the PCI patients may be considered a positive finding along with reduced overall mortality with this strategy. The PCI-based strategy was associated with a reduced risk of large prior MI leading cardiac death and "at least, no increase in the long-term risk following smaller non-fatal MI." It is of interest that a considerable number of the trials comparing a PCI strategy with a medical treatment strategy do not come to the same conclusion, although the overall pooled analysis in this report does represent a large data base, with an average follow-up period of 51 months. The consistency of a 20% reduction in the odds ratio of death with PCI vs continued medical treatment has been suggested in the past, but has not been believed to be a substantial finding. This meta-analysis answer is consistent with previous reports comparing the two strategies. Several large trials that may be familiar to readers include ACME-1 and ACME-2, reported in 1997, RITA-2 in 2003, and in the recently published COURAGE trial in 2007. Of note, DANAMI, SWISS-II, and INSPIRE did find an improvement in non-fatal MI with OMT only.
In PCI subjects, the data analysis in the current report focuses on fatal events and MI. Early relief of angina with revascularization has clearly been shown to be robust in many early trials, but with perhaps regression to the mean, resulting in equal event rates by two years. One major issue relates to the availability of new therapies over time, with the probability that either PCI and/or optimal medical therapy have become more effective during the meta-analysis period of 17 years. The answer is clearly a "yes," and this underscores the conclusion of the meta-analysis that it may favor one strategy over the other because of the greater improvement in effectiveness in one therapy vs another. Of probable great importance, standard medical therapy today is very different from five, 10, or 15 years ago, and includes the currently recommended cocktail of aspirin, a statin, a beta blocker, clopidogrel, and in many cases, an ACE inhibitor. Cath lab techniques have also improved over the time period of the report, particularly the use of stenting in many of the recent reports. It is arguable whether there has been a greater improvement in PCI technique vs the widespread use of protective medical therapy over the past 15-year period. In any case, these data are reassuring, indicating that an early invasive approach in stable patients with CAD appears to do no harm and may be better for some stable angina subjects who continue to have angina. Certainly, most previous studies have favored an early revascularization strategy, particularly with ACS patients. The impressive benefits of medical therapy in COURAGE and other trials suggests the conclusion that we are probably doing no harm with cath and angioplasty in stable patients.
Note: In an accompanying commentary, Dr. Robert O'Rourke comments about the meta-analysis and concludes that aggressive medical therapy should be the approach to stable symptomatic angina, with PCI or CABG only for "moderate to severe angina whose symptoms persist." (O'Rourke RA. J Am Coll Cardiol. 2008: 52:905-907)