Quinapril Anti-Ischemia and Symptoms of Angina Reduction - QUASAR

Description:

The goal of the Quinapril Anti-Ischemia and Symptoms of Angina Reduction (QUASAR) trial was to evaluate the efficacy of the angiotensin-converting enzyme (ACE) inhibitor quinapril compared with placebo in the reduction of transient ischemia in patients with coronary artery disease (CAD) with stable angina.

Hypothesis:

Treatment with quinapril will be associated with a reduction in transient ischemia compared with placebo in patients with CAD with stable angina.

Study Design

Study Design:

Patients Enrolled: 336
Mean Follow Up: 16 weeks
Mean Patient Age: Mean age 64.5 years
Female: 20

Patient Populations:

CAD documented by any of the following: ≥60% diameter stenosis in a major coronary artery, Q-wave MI, or an abnormal stress test by echocardiography or radionuclide imaging; or abnormal ETT, limited by angina pectoris occurring within eight minutes and accompanied by an ischemic-type ST-segment response

Exclusions:

Likely to confound the interpretation of response measures, including severe bronchospastic lung disease, cor pulmonale, recent unstable angina, angina precipitated by correctable anemia or metabolic factors, significant uncorrected valvular or congenital heart disease, recent revascularization, left ventricular hypertrophy with ST-T-segment abnormalities, paced rhythm, uncontrolled ventricular or supraventricular arrhythmias, left or right bundle branch block, atrioventricular conduction defects and/or resting ST-segment depression, insulin-dependent or uncontrolled type 2 diabetes, or initiation or termination of hormone replacement therapy or lipid-lowering drugs within two months; increased risk of severe hypotension with ACE inhibitors, including renal artery stenosis or hypotension; definite indication for ACE inhibitors, including recent MI, uncontrolled hypertension, or heart failure; or any exposure to ACE inhibitors within two weeks of entering the baseline period

Primary Endpoints:

Time to onset 1 mm ST-segment depression during ETT at eight weeks

Secondary Endpoints:

Time to onset of angina during exercise, exercise duration, number and duration of ischemic episodes during ambulatory ECG monitoring, ischemic burden, and severity of angina by the Seattle Angina Questionnaire at eight weeks

Drug/Procedures Used:

Patients were randomized to quinapril (40 mg/day; n=177) or placebo (n=159) for eight weeks. In the next eight-week period, patients randomized to 40 mg quinapril continued on 40 mg, while those assigned to placebo were titrated to 80 mg/day. Patients underwent exercise treadmill testing (ETT), ambulatory ECG monitoring, and the Seattle Angina Questionnaire at baseline, eight weeks, and 16 weeks.

Principal Findings:

There was no difference between treatment groups in the primary endpoint of time to onset of 1 mm ST depression during ETT at eight weeks (4.8 minutes with quinapril vs. 4.7 minutes with placebo, p=NS) or 16 weeks (5.2 minutes vs. 5.0 minutes, p=NS). There was also no difference in total exercise time at eight weeks (6.7 minutes vs. 6.4 minutes) or 16 weeks (6.9 minutes vs. 6.7 minutes).

Mean Seattle Angina Questionnaire scores were similar between the two treatment groups at baseline, eight weeks, and 16 weeks. There was no difference in adverse events in either arm and at either quinapril dose (40 mg and 80 mg). There were also no changes in serum electrolytes or renal function.

Interpretation:

Among patients with CAD with stable angina, treatment with the ACE inhibitor quinapril was not associated with a difference in transient ischemia at eight or 16 weeks compared with placebo. Multiple studies have shown a reduction associated with the use of ACE inhibitors in the clinical endpoints of death and myocardial infarction (MI) in high-risk patients, including those with heart failure, MI, and hypertension. However, the present trial is the first randomized, blinded, placebo-controlled trial to evaluate the effects of ACE inhibitors on transient myocardial ischemia in a low-risk, stable angina population.

References:

Pepine CJ, Rouleau JL, Annis K, et al., for the QUASAR Study Group. Effects of angiotensin-converting enzyme inhibition on transient ischemia: the Quinapril Anti-Ischemia and Symptoms of Angina Reduction (QUASAR) trial. J Am Coll Cardiol 2003;42:2049-59.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Echocardiography/Ultrasound, Hypertension, Chronic Angina

Keywords: Electrolytes, Depression, Coronary Artery Disease, Myocardial Infarction, Radioisotopes, Angina, Stable, Tetrahydroisoquinolines, Constriction, Pathologic, Electrocardiography, Heart Failure, Questionnaires, Hypertension, Echocardiography, Exercise Test


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