Comparison of Subgroups Assigned to Medical Regimens Used to Suppress Cardiac lschemia (the Asymptomatic Cardiac lschemia Pilot [ACIP] Study) Craig M. Pratt, MD, Robert P. McMahon, PhD, Sidney Goldstein, MD, Carl J. Pepine, MD, Thomas C. Andrews, MD, lhor Dyrda, MD, William H. Frishman, MD, Nancy L. Geller, PhD, James A. Hill, MD, Nancy A. Morgan, RPH, MBA, Peter H. Stone, MD, Genell L. Knatterud, PhD, George Sopko, MD, and C. Richard Conti, MD, for the ACIP Investigators This report focuses on the subset of 235 patients from the Asymptomatic Cardiac lschemia Pilot (ACIP) study receiving randomly assigned medical therapy to treat angina and suppress ischemia detected on ambulatory electrocardiography: 121 patients received the se- quence of atenolol and nifedipine, and 114 diltiazem and isosorbide dinitrate. After 12 weeks of therapy, the primary end point (absence of ambulatory electrocar- diographic (ECG) ischemia and no clinical events) was reached in 47% of atenolol/nifedipine- versus 31% of diltiazem/isosorbide dinitrate-treated patients (ad- justed p=O.O3). A trend to increased exercise time to ST depression was seen in the atenolol and nifedipine ver- sus diltiazem and isosorbide dinitrate regimens (median treadmill duration 5.8 vs 4.8 minutes; p=O.O4). How- ever, when adiusted for baseline imbalances in ambu- latory ECG ischemia, the 2 medical combinations were similar in suppression of ambulatory ECG ischemia. In both medication regimens, an association between mean heart mte and ischemia on ambulatory electro- cardiography after 12 weeks of treatment was observed so that patients on either regimen with a mean heart rate >80 beats/min had ischemia detectable almost twice as often as those with a mean heart rate <70 beats/min (p <O.OOl). (Am J Cardiol 1996;77: 1302- 1309) C ardiac ischemia is associated with increased mor- bidity and mortality. Although the elimination of symptomatic cardiac ischemia or angina is a tradi- tional treatment goal, it has not been established to what degree this improves long-term outcome. Sev- eral studies have established that most episodes of cardiac ischemia are asymptomatic.‘- The Asymp- tomatic Cardiac Ischemia Pilot (ACIP) study is unique in that it is a prospective, randomized trial formally testing various treatment strategies to sup- press cardiac ischemia. A comparison of the outcome of the 2 medical treatment strategies compared with From the Section of Cardiology, Department of Medicine, Baylor Col- lege of Medicine, Houston, Texas. This work was presented, in part, at the Scientific Session of the American Heart Association in Dallas, Texas, in November 1994. This study was funded by Research Con- tracts HV-90-07, HV-9048, and HV-91-05 to HV-91-14 from the National Heart, lung, and Blood Institute, Cardiac Diseases Branch, Division of Heart and Vascular Disease. National Institutes of Health Bethesda, Maryland. Stud Y medications and placebo were donated by Zeneca Pharmaceutics s Group, Wilmington, Delaware; Marion- Merrell Dow, Kansas City, Missouri; and Pfizer, New York, New York. Support for electrocardiographic data collection was provided in part by Applied Cardiac Systems, laguna Hills, California; Mar- quette Electronics, Milwaukee, Wisconsin; Mortara Instrument, Mil- waukee, Wisconsin; and Qutnton Instruments, Seattle, Washington. Some centers had partial support from General Clinical Research Center grants. A complete list of the ACIP investigators and centers participating in the ACIP study was published previously in.JAm Co// Cardiol 1995;26:594-605. M anuscript received September 25, 1995; revised manuscript received and accepted February 1, 1996. Address for reprints: Genell Knatterud, PhD, ACIP Clinical Coor- dinating Center, Maryland Medical Research Institute, 600 Wynd- burst Avenue, Baltimore, Maryland 2 12 10. 1302 0 1996 by Excerpto Medica, Inc. All rights reserved. revascularization has been reported elsewhere.’ The purpose of this report was to compare suppression of cardiac ischemia between 2 medication regimens among patients (approximately two thirds of the pa- tients) for whom random drug assignment was fea- sible. METHODS Study Population: The details of the ACIP study design have been summarized elsewhere.8 As pre- viously reported,9 data from 60 patients enrolled at 1 clinical center were excluded, including 4 patients assigned to medical therapy with randomly assigned medication regimens. Patients were eligible for en- rollment in ACIP if they had coronary artery disease associated with 2 1 episode of asymptomatic cardiac ischemia on the ambulatory electrocardiogram. This was defined as rl mm of ST depression for 2 1 minute duration as well as ischemia demonstrated on an ACIP protocol treadmill test or an alternative stress test. To be eligible, patients were required to have revascularizable coronary artery disease ( 250% luminal diameter narrowing) on a coronary angiogram. Exclusion criteria included the presence of a recent myocardial infarction, unstable angina, or the inability to take any of the study medications. All patients gave informed consent before enrollment; the ACIP protocol and consent forms were approved by the institutional review boards at each participat- ing clinical unit. Study design: This study focused on the 2 phar- macologic ACIP limbs: ( 1) angina-guided, and (2) 0002.9 149/96/s 15.00 PII SOOO2-9 149(96)00 196-8