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Aspirin Use is Detrimental in Patients With Heart Disease Who Are Being Treated With ACE Inhibitors.

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Angiotensin-converting enzyme (ACE) inhibitors and aspirin are both recommended treatments for the management of patients with heart disease. In fact, the 2011 update of the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) guideline on secondary prevention of atherosclerotic disease1 recommends aspirin as a Class I indication for all patients with coronary artery disease (CAD), while ACE inhibitors are recommended as either a Class I or Class IIa recommendation in all patients depending on the underlying comorbid conditions. Despite this, there is some concern that the combined use of these two classes of agents together may cause deleterious effects in some patients. The purpose of this paper is to examine the literature that supports the contention that aspirin use is deleterious in patients with heart disease who are being treated with ACE inhibitors.

ACE inhibitors have clearly been shown to reduce the risk of morbidity and mortality in a variety of patients with cardiovascular disease. In the SOLVD2 and VHeFT-II3 studies, for example, the use of enalapril improved survival in patients with chronic congestive heart failure (CHF), regardless of patient functional status. In two other large, randomized controlled trials (ISIS-4 and GISSI-3),4,5 the use of either lisinopril or captopril in post-myocardial infarction (MI) patients was also associated with lower death rates, particularly in those with concomitant left ventricular dysfunction. Similar results have also been demonstrated with other ACE inhibitors, suggesting that these benefits are due to a class effect and are not confined to particular agents. Like the ACE inhibitors, aspirin use has clearly been shown to be beneficial in patients with certain types of cardiovascular disease. In the ISIS-2 trial,6 for example, the effect of once-daily administration of aspirin on reducing mortality was equivalent to that of the thrombolytic streptokinase when given to patients with an acute MI. Similar benefits have been shown in the primary prevention of CAD and the secondary prevention of stroke, which has led many organizations to recommend aspirin as the standard of care for patients at elevated risk for CAD.

Due to the profound benefits observed with each of these two drug classes, it is not surprising that many patients with established cardiovascular disease are often prescribed both aspirin and ACE inhibitors with the assumption that the combined use will provide additive benefits over either one alone. Unfortunately, this assumption has not necessarily been evaluated in controlled clinical trials, and there are theoretical reasons why the combination of these two drugs might not produce complementary benefits.

The proposed mechanisms of ACE inhibitors involve a reduction in the circulating levels of angiotensin-II and aldosterone, both of which are deleterious due to their vasoconstrictive and fluid-retention effects, as well ...

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