What Is the Optimal Blood Pressure and Drug Therapy for Patients With Coronary Artery Disease?

Abstract

THE NUMBER OF PERSONS WITH CORONARY ARTERY DISease (CAD) is increasing dramatically, with more patients surviving myocardial infarction (MI), the aging of the population, and the increasing prevalence of diabetes, obesity, and inactivity. As a result, deaths from cardiovascular disease have increased about 2.5% per year over the past decade. Yet there is a paucity of prospective randomized trial data on the relative impact of various drugs and blood pressure levels on adverse outcomes in patients with CAD. This information is critical to current management of these patients for many reasons. Past experiences have demonstrated that patients with myocardial ischemia may react differently to many drugs that otherwise appear safe (eg, nifedipine, phosphodiesterase inhibitors, antiarrhythmic agents, rofecoxib) and reducing blood pressure in patients with CAD is very complex. To this end, 2 large randomized clinical trials examining blood pressure treatment in patients with CAD provide important new information on this issue. In the first of these reports, the recently published International Verapamil-trandolapril Study (INVEST), a calcium antagonist strategy (verapamil SR-trandolapril) and a -blocker strategy (atenolol-hydrochlorothiazide) were equivalent in preventing death, MI, or stroke in hypertensive patients with CAD. Both multidrug strategies provided excellent blood pressure control (eg, 70% of patients with blood pressure 140/90 mm Hg) and were effective in decreasing angina (from 67% at study entry to 28% at 2 years) with infrequent need for revascularization (eg, 2%). But the calcium antagonist strategy was somewhat more effective in reducing angina frequency and was associated with significantly less new-onset diabetes. Furthermore, the nadir in the systolic blood pressure–adverse outcomes relationship was approximately 120 mm Hg. In this issue of JAMA, Nissen and colleagues report the results of the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) study. Patients with CAD and on-treatment blood pressure within the socalled normal range ( 140 mm Hg) were randomly assigned to receive placebo, a calcium antagonist (amlodipine), or an angiotensin-converting enzyme inhibitor (enalapril) to evaluate the effects of further blood pressure lowering. In a substudy, the authors used a novel design feature (that is likely a prototype for future studies) to directly examine blood pressure and drug effects on coronary atherosclerosis progression using intravascular ultrasound (IVUS) as pioneered by this group for lipid treatment studies. Overall the patients were very well managed, with high use of aspirin (95%) and statins (83%). Compared with placebo, amlodipine and enalapril reduced blood pressure similarly (approximately 5 mm Hg systolic) when added to -blockers (approximately three fourths of the patients) with or without diuretics (approximately one third of the patients). Results suggested that patients assigned to amlodipine fared better in terms of fewer ischemia-related events (eg, hospital admissions for angina, coronary revascularizations) with a trend for reduced death, MI, and stroke. This clinical benefit of amlodipine persisted in the subgroup with diabetes. Of more interest, progression of coronary atherosclerosis was documented in placebo-assigned patients undergoing serial IVUS evaluation. But no progression was observed with either amlodipine or enalapril, suggesting that perhaps the lower blood pressure may be more important than the class of agent used. With both active treatments combined there appeared to be no atherosclerosis progres-