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CLINICAL RESEARCH: CLINICAL TRIALS

Effects of angiotensin-converting enzyme inhibition on transient ischemia

The quinapril anti-ischemia and symptoms of angina reduction (QUASAR) trial

Carl J. Pepine, MD, MACC^*,*, Jean-Lucien Rouleau, MD, FACC, Karen Annis, MPH, Anique Ducharme, MD, Patrick Ma, MD, FACC^||, Jacques Lenis, MD, FACC^¶, Richard Davies, MD, FACC^#, Udho Thadani, MD, FACC^**, Bernard Chaitman, MD, FACC, Harry E. Haber, MPH, S. Ben Freedman, MB, PhD, FACC, Milton L. Pressler, MD, FACC, Bertram Pitt, MD, FACC QUASAR Study Group

^* University of Florida College of Medicine, Division of Cardiovascular Medicine, Gainesville, Florida, USA
University Health Network, Division of Cardiology, Toronto, Ontario, Canada
Pfizer, Inc., Ann Arbor, Michigan, USA
Montreal Heart Institute, Montreal, Quebec, Canada
^|| Heart Health Institute, Research Center, Calgary, Alberta, Canada
^¶ Invascor Clinical Research, Quebec, Canada, Centre Hospitalier Pierre Boucher, Longueuil, Quebec Canada
^# Ottawa Civic Hospital, Ottawa, Ontario, Canada
^** University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Cardiology Section, Oklahoma City, Oklahoma, USA
St. Louis University ECG Core Laboratory, St. Louis, Missouri, USA
Concord Repatriation General Hospital, Department of Cardiology, University of Sydney, Sydney, Australia
University of Michigan Medical Center, Department of Medicine, Ann Arbor, Michigan, USA

Manuscript received April 25, 2003; revised manuscript received July 9, 2003, accepted July 22, 2003.

^* Reprint requests and correspondence: Dr. Carl J. Pepine, University of Florida College of Medicine, Division of Cardiovascular Medicine, P.O. Box 100277, Gainesville, Florida 32610-0277, USA
pepincj{at}medicine.ufl.edu

OBJECTIVES: We sought to determine whether angiotensin-converting enzyme inhibition (ACE-I) (i.e., quinapril) prevents transient ischemia (exertional and spontaneous) in patients with coronary artery disease (CAD).

BACKGROUND: It is known that ACE-I reduces the risk of death, myocardial infarction (MI), and other CAD-related outcomes in high-risk patients. Numerous studies have confirmed that ACE-I improves coronary flow and endothelial function. Whether ACE-I also decreases transient ischemia is unclear, because no studies have been adequately designed or sufficiently powered to evaluate this issue.

METHODS: Using a randomized, double-blinded, placebo-controlled, multicenter design, we enrolled 336 CAD patients with stable angina. None had uncontrolled hypertension, left ventricular (LV) dysfunction, or recent MI, and all developed electrocardiographic (ECG) evidence of ischemia during exercise. They were randomly assigned to one of two groups: 40 mg/day quinapril (n = 177) or placebo (n = 159) for 8 weeks. Patients then entered an additional eight-week treatment phase to examine the full dose range. Those assigned to 40 mg quinapril continued that dose and those assigned to placebo were titrated to 80 mg/day. Treadmill testing, the Seattle Angina Questionnaire, and ambulatory ECG monitoring were used to assess responses at baseline and at 8 and 16 weeks.

RESULTS: The groups did not differ significantly at entry or in terms of indexes assessing myocardial ischemia at 8 or 16 weeks of treatment. In this low-risk population, ACE-I was not associated with serious adverse events.

CONCLUSIONS: Our findings suggest short-term ACE-I in CAD patients without hypertension, LV dysfunction, or acute MI is not associated with significant effects on transient ischemia.

Abbreviations and Acronyms   ACE-I = angiotensin-converting enzymeinhibition/inhibitor   CAD = coronary artery disease   ECG = electrocardiogram/electrocardiographic   ETT = exercise treadmill test/testing   LV = left ventricular   MI = myocardial infarction   QUASAR = Quinapril Anti-ischemia and Symptoms of Angina Reduction trial

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