COUNTERPOINT: Mechanical Treatment of Atherosclerosis Is Not a Cure

Dr Ellestad’s concern regarding the long-term effects of ischemia in medically treated patients vs revascularized patients has also occurred to me. In the early 1990s it was postulated that ischemia may be beneficial in terms of encouraging collateralization of the coronary arteries. We learned from 2 studies of silent ischemia, the Asymptomatic Cardiac Ischemia Pilot (ACIP)1 study and the Atenolol Silent Ischemia Study (ASIST),2 that ischemia in stable patients is not beneficial. The ACIP trial randomized 558 patients to angina-guided therapy (essentially no treatment), medical therapy (atenolol-nifedipine or diltiazem-isosorbide dinitrate), or revascularization (angioplasty or bypass). The 1-year mortality rate was 4.4% in the angina-guided group, 1.6% in the medical therapy group, and 0% in the revascularization group. In ASIST, 306 patients with silent ischemia were randomized to atenolol vs placebo. There was a strong trend toward improvement in hard cardiac events (risk ratio, 0.55) in the atenolol group. Compared with modern therapy, the medical treatment was grossly inadequate in that neither of these studies described how many patients were taking aspirin, none were prescribed statins, and none were taking angiotensin-converting enzyme (ACE) inhibitors. One could also argue that the use of calcium channel blockers was not beneficial and possibly harmful in patients with left ventricular (LV) dysfunction. Once we all agree that ischemia is harmful, the question becomes “Can we impact the disease and how?” Prior to the development of angioplasty, there were several early studies investigating coronary artery surgery to revascularize patients with stable angina. These studies were the VA Coronary Artery Bypass Surgery Cooperative Study Group,3 the Coronary Artery Surgery Study,4 and the European Coronary Surgery Study Group.5 Retrospective analyses of these trials suggested that survival was superior with coronary artery bypass surgery compared with medical therapy in patients with left main disease, proximal left anterior descending coronary artery disease (proximal to the first septal perforator), and 3-vessel coronary artery disease with LV dysfunction. As in the trials noted above, the use of statins and ACE inhibitors was nonexistent and calcium channel blockers were common. Following these landmark trials there have been numerous trials investigating one form of revascularization vs another, but there has been a paucity of data comparing medical and mechanical treatment of stable coronary artery disease. Over the past 2 decades, revascularization has been used to treat patients with progressively lower amounts of atherosclerotic burden. Medical and surgical therapies have advanced considerably during the past 2 decades. Statin therapy, ACE inhibitors, and antiplatelet therapy have been developed. Surgical techniques have similarly improved with the introduction of newer cardioplegia agents and techniques and the utilization of the internal mammary artery as the primary conduit for the left anterior descending (LAD) artery. Repeated trials comparing medical vs interventional therapy for stable coronary disease are necessary to know which of these competing treatments is preferable for which patients. The Optimal Medical Therapy With Or Without Percutaneous Coronary Intervention for Stable Coronary Disease (COURAGE) trial6 was performed to guide us in this ongoing question. It included 2287 patients with objective evidence of ischemia who were randomized to optimal medical therapy (OMT) vs percutaneous coronary intervention (PCI) plus OMT. Forty-eight percent of patients underwent treadmill testing with an average exercise duration of 7 minutes. Patients with a markedly positive stress test result were excluded. The average baseline ejection fraction was 61%, and 34% of patients were described as having proximal LAD disease (undefined). During the 2.5- to 7-year follow-up, there was no difference between the 2 groups in the primary end point of all-cause mortality and nonfatal myocardial infarction. Given the baseline normal ejection fraction and exclusion of patients with markedly positive stress test results, one might have predicted no difference in outcome based on what we know from the older surgery vs medical therapy trials. The number of patients who were angina-free was different and somewhat supports Dr Ellestad’s concern regarding untreated ischemia potentially leading to long-term cardiac fibrosis. At 1 year, 66% of PCI patients were angina-free vs 58% in the medically treated group. At 2 years, the difference was 72% vs 67% favoring PCI. However, at 5 years of follow-up, there was no difference between the 2 groups, with 74% and 72% being angina-free. While the early differences are statistically significant, it is unclear whether these differences are clinically meaningful. Using a long-term outlook, by 5 years there was no difference between the 2 groups, thereby arguing that PCI provides no long-term benefit against ischemia compared with OMT and will not prevent long-term cardiac fibrosis. The question remains, does angina indicate overall ischemic burden? In a scintigraphic substudy of the COURAGE trial, 314 patients underwent myocardial perfusion stress imaging at baseline and at 6 and 18 months.7 The primary end point was a >5% reduction in ischemic burden based on quantitative determination of extent of stress-induced myocardial ischemia. The primary end point occurred in 33% of PCI patients compared with 19% of OMT patients (P=.0004). This finding is consistent with the slight angina difference noted in the main trial. However, stated another way, 67% of PCI patients failed to significantly improve and 81% of optimal medical therapy patients failed to significantly improve. We do not know whether there would be any difference in scintigraphic ischemic burden at the 5-year mark where there was no difference in angina in the main study. In conclusion, the angina data from the main COURAGE trial suggests that there is no difference in ischemic burden at 5 years. Data from the scintigraphic substudy suggests that there is a slight clinical difference between OMT and PCI plus OMT at 18 months. Whether this difference persists over a longer period is unknown. There is no difference in hard end points at an average 4.6-year follow-up between OMT and PCI plus OMT for patients with preserved LV ejection fraction and absence of a markedly positive treadmill test result. All of this data suggests that there is no excess ischemic burden in OMT patients compared with PCI plus OMT patients and that OMT is not a prescription to reduce LV function.