Abstract & Commentary
Synopsis: A new randomized trial using either a calcium channel blocker or an ACE inhibitor to lower systolic blood pressure to the low 120s prevented cardiac events in patients with coronary artery disease (CAD) compared with systolic blood pressures around 130.
Source: Nissen SE, et al. JAMA. 2004;292:2217-2226.
Since 2000, controlled clinical trials have been published suggesting that lower blood pressures than 140/90 mm Hg may prevent coronary events.1-3 These studies have resulted in revised recommendations for blood pressure lowering in patients at high risk for coronary artery disease, such as those with combined hypertension and diabetes. A new category of borderline hypertension has been established for patients with blood pressures above 130/80. Controversy still exists over what the optimal blood pressure might be for patients with existing coronary artery disease.
This study from the Cleveland Clinic Foundation conducted a double-blind randomized multicenter 2 year trial of amlodipine (10 mg) or enalapril (20 mg) or placebo in 1991 patients with angiographically documented CAD. The study was funded by Pfizer, the maker of the most common brand of amlodipine (Norvasc). While the results were the most impressive with amlodipine, both drugs reduced coronary events and were not statistically different in head to head comparison.
The baseline blood pressure averaged 129/78 for all patients. In the amlodipine treated group, the average decrease was 4.8/2.5 mm Hg, and in the enalapril treated group, the average decrease was similar at 4.9/2.4 mm Hg. The amlodipine treated group had a 31% relative reduction in cardiovascular events (6.5% absolute reduction), and the enalapril treated group had a 15.3% relative reduction (2.9% absolute reduction). The number needed to treat for amlodipine was 16 patients.
Comment by Joseph E. Scherger, MD, MPH
The prevention of myocardial infarction in high risk patients is becoming more precise. During the past 5 years, we have witnessed revised guidelines for the management of lipids and blood pressure. The preferred lipid lowering numbers, such as LDL-C below 100 in patients with type 2 diabetes, have become well established. Blood pressure seems more elusive, probably because of its labile nature and relative uncertainty in its measurement. Blood pressure measurement is not a lab test, but a procedure we perform in the office. And low blood pressure can make us nervous, especially in the elderly who are at risk for stroke.
I have generally liked the reading of 130/80 in patients over 50 years old. Now I must revise my thinking and aim for lower blood pressures in patients at risk for or with established CAD. In the same issue of JAMA as this clinical trial, Pepine writes an editorial, What is the Optimal Blood Pressure and Drug Therapy for Patients with Coronary Artery Disease?4 He argues persuasively for lowering the systolic blood pressure to 120 in patients with CAD based on all the current literature. An anti-atherosclerotic effect was seen in the patients in this trial, and seems to be more related to the lowering of blood pressure than to a drug effect. This benefit of lower blood pressures increases with the age of the patients.
So, drug treatment to lower blood pressure should become part of treating all patients with CAD and a systolic blood pressure significantly above 120 mm Hg. Certainly, there will be new formal recommendations. Calcium channel blockers and ACE inhibitors have been shown to benefit these patients, not because others have not, but because these are the drugs the have been studied (thanks to financial support from their manufacturers). Beta-blockers and diuretics may provide similar benefit. Most of the patients in this study were taking other important medications such as aspirin (95%) and statins (83%).
Treating normal patients with medications is not a concept I take to easily. However, when patients have established high risk diseases, such as type 2 diabetes or CAD, then the definition of normal is changed.
Dr. Scherger, Clinical Professor, University of California, San Diego, is Associate Editor of Internal Medicine Alert.
1. Heart Outcomes Prevention Evaluation Study. N Engl J Med. 2000;342:145-153.
2. Fox KM, et al. Lancet. 2003;362:782-788.
3. Pitt B, et al. Circulation. 2000;102:1503-1510.
4. Pepine CJ. JAMA. 2004;292:2271-2273.