ACE Inhibitors and Aspirin
ABSTRACT & COMMENTARY
Synopsis: If the results of this study are reproducible, it would suggest that any attenuating effects of ASA can be avoided by sticking to baby ASA (81 mg).
Source: Guazzi MD, et al. Clin Pharmocol Ther 1998;63: 79-86.
Cyclooxygenase inhibitors, such as aspirin (ASA), may counteract the vasodilatory effects of angiotensin converting enzyme (ACE) inhibitors by blocking prostaglandin effects. ACE inhibitors increase prostaglandin levels by increases in bradykinin levels. Thus, Guazzi and colleagues studied 26 patients with mild to moderate hypertension on enalapril monotherapy (40 mg/day) and 26 patients with severe hypertension on enalapril, long-acting nifedipine (30 mg/day), and atenolol (50 mg/day). ASA was tested at doses of 100 mg/day and 300 mg/day. Each drug combination was administered for five days, and an attenuation of ACE inhibitor effect was defined as a 20% reversal of the blood pressure lowering effect by ASA. The 100 mg dose produced no effects. The 300 mg dose antagonized the beneficial blood pressure lowering effects of drug therapy in both groups in about 50% of the patients, which were then termed responders to ASA. No clinical difference between the responders and the nonresponders could be identified. Guazzi et al conclude that about half of the patients on ACE inhibitor therapy for hypertension are susceptible to 300 mg of ASA/day attenuating hypertension control, regardless of the severity of their hypertension.
COMMENT BY MICHAEL H. CRAWFORD, MD
The major limitations of this study were the fixed sequence of drug administration and the short treatment periods (5 days) without drug washout periods in-between. On the other hand, the investigators and the patients were blinded to the treatment, and the short treatment periods enhanced compliance. Several questions remain about this issue. Whether this attenuating effect will persist long term is unknow n. Whether it will apply to heart failure patients treated with ACE inhibitors is unknown. Also, the mechanism of this effect was not elucidated in this study. If the results are reproducible, it would suggest that any attenuating effects of ASA can be avoided by sticking to baby ASA (81 mg). (Dr. Crawford is Robert S. Flinn Professor, Chief of Cardiology, University of New Mexico, Albuquerque.)