LETTERS TO THE EDITOR
Reply
Jonathan Leor, MD, FACCa,
Shmuel Gottlieb, MDa and
Solomon Behar, MDa
a Department of Cardiology, Soroka Medical Center, P.O. Box 151, Beer Sheva 84105, Israel
jleor{at}bgumail.bgu.ac.il
We thank Levi et al. for their thoughtful comments. They proposed a fresh explanation to our clinical observation (1). Although previous data suggest a negative interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors (2), Levi et al. propose a "positive" interaction. We (1) and others (2) were not aware of the mechanism proposed by Levi et al. They suggest that bradykinin facilitates norepinephrine release from cardiac sympathetic nerves during ischemia, and this effect is potentiated by ACE inhibition (3,4). Aspirin might attenuate bradykinin-mediated norepinephrine release from nerve endings during myocardial ischemia. A reduction in plasma norepinephrine might be beneficial owing to the deleterious effects of norepinephrine on the heart. Thus, aspirin may prevent one of the adverse effects of bradykinin during myocardial ischemia. The mechanism proposed by Levi et al. to explain our findings is unique and attractive, but is derived from an isolated guinea pig heart model and specimens of the human right atrium. Thus, these exciting findings need confirmation in a clinical trial that will also evaluate the appropriate dose of aspirin in patients treated with ACE inhibitors.
The neurohormonal activation in patients with heart failure or myocardial ischemia is complex and sometimes contradicts our conventional understanding. For example, we are disappointed by the preliminary results of the recent Moxonidine Congestive Heart Failure Trial (MOXCON) study (5). The study was terminated early, and the investigators failed to confirm the hypothesis that a reduction in plasma norepinephrine by moxonidine can reduce mortality in patients with heart failure.
Data derived from the Evaluation of Losartan in the Elderly (ELITE-2) study, which compared mortality in patients treated with captopril versus losartan, and data from the Warfarin-Antiplatelet Trial Chronic Heart Failure (WATCH) trial, which evaluates aspirin, clopidogrel or warfarin in patients with heart failure, may help to clarify the controversy surrounding the relation between aspirin and ACE inhibitors. Until then, on the basis of our observation (1) and the findings of Levi et al. (3,4), we suggest that administration of low dose aspirin to patients taking ACE inhibitors is safe and may have an additive beneficial effect during myocardial ischemia.
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References
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- Leor J, Reicher-Reiss H, Goldbourt U, et al. Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors—a cohort study of 11,575 patients with coronary artery disease. J Am Coll Cardiol. 1999;33:1920–1925[Abstract/Free Full Text]
- Teerlink JR, Massie BM. The interaction between ACE-inhibitors and aspirin in heart failure: torn between two lovers. Am Heart J. 1999;138:193–197[CrossRef][Medline]
- Hatta E, Maruyama R, Marshall SJ, Imamura M, Levi R. Bradykinin promotes ischemic norepinephrine release in guinea pig and human hearts. J Pharmacol Exp Ther. 1999;288:919–927[Abstract/Free Full Text]
- Seyedi N, Maruyama R, Levi R. Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release? J Pharmacol Exp Ther. 1999;290:656–663[Abstract/Free Full Text]
- Coats AJ, Coats AJ. Heart Failure 99—The MOXCON Study. Int J Cardiol. 1999;71:109–111[CrossRef][Medline]
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