ABSTRACTS

THE EFFECTIVENESS OF COMBINED VERAPAMIL AND NITRATE THERAPY IN PRINZMETAL'S VARIANT ANGINA Albert E. Rairner, MD, FACC; William Gaston, MD, FACC; Robert A. Chahine, MD, FACC; Robert Fulweber, MD, FACC; Don Rochelle, MD, FACC; Richard R. Miller, MD, FACC; Robert J. Luchi, MD, FACC, Baylor College of Medicine and VA Medical Center, Houston, Texas.

Prinzmetal's variant angina which does not respond to nitrates (N) can pose a serious therapeutic problem. We studied the effectiveness of verapamil, a calcium antag- onist, in combination with nitrates in 10 patients (pts), 4 males and 6 females, ages 42 to 74, (mean 57) years, who were refractory to nitrates alone. Angina frequency was l-3 (6 pts), 3-5 (3 pts) and , 5 (1 pt) attacks per day. ST segment elevation during pain was documented in all. Serious arrhythmias during attacks included com- plete heart block (2 pts) and ventricular tachycardia (3 pts). Coronary arteries were normal in 7 and 3 had single vessel disease. Coronary artery spasm was docu- mented in 7 pts during spontaneous (3 pts) or provoked attacks (4 pts). Verapamil, 40-120 (avg 80 mg) q 6 h was, initially, used alone in 3 pts. One became asympto- matic and 2 improved, but still had variant angina at- tacks (> l/week). In 9 pts verapamil plus nitrates elim- inated attacks in 7 pts, with marked improvement (<l attack/month) in 2 pts. Asymptomatic or improved status has been maintained during 3-12 month follow-up (mean 6.2). No episodes of ST elevation or serious arrhythmias have been noted on ambulatory 24 hour ECG obtained q 2-3 mos. Importantly, the only side effect was GI distress in 1 pt necessitating reduction in dosage of verapamil. Thus, verapamil in combination with nitrates is highly effective and safe in the treatment of Prinzmetal's variant angina.

EFFECT OF NIFEDIPINE ON EXERCISE TOLERANCE IN CORONARY ARTERY DISEASE James V. Faris, ND, FACC; Richard H. Childreee, MD, FACC; August M. Watanabe, MD, FACC, V.A. Medical Center and Rrannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana

Nifedipine, a calcium-antagonist and arterial vasodila- tor,isknown to be effectiveintreatment of Prinametal's angina, but may also be effective in angina due to fixed occlusive disease. To assees the effect of Nifedipine on treadmill exercise tolerance, nine stable angina pa- tients with proven coronary disease underwent aerial symptom limited exercise testing using a modified Balke protocol. Average exercise time, blood pressure response, double product and maximal ST-segment depression were compared for two control (placebo) treadmills vereus the average of two Nifedipine treadmills. In a eingle-blind fashion, each patient received placebo or Nifedipine lo-20 mgm Q8H with a dose l-2 hours prior to treadmill testing. All antianginal drugs except nitroglycerin were proeoribed. The results are tabulated below:

Exercise Time(Seconds) Control Nifedipine Sig. 321f74.7 434f67.6 P<.OOl

Heart Rate 135i11.5 148f18.1 PC.01 Systolic BPOmnHg) 174f15.4 172f12.0 n.6. Diastolic BPOnmIig) 105f 9.4 91f 5.9 PC.001 Mean BP(mmIig) 127f10.6 117f 6.7 pe.01 Double Product(HRxSBP/lOO) 235f24.6 259f28.3 pg.01 Maximal ST-Depression 1.9i 0.7 1.5f 0.8 n.6. The data ouggest Nffedipino significantly improves exer- cise tolerance, double product and peak heart rate achieved. The significant drop in mean and diastolic blood pressures may also play a role in the observed augmentation of exercise tolerance by reducing myocardial oxygen consumption.

SYSTEMIC AND CORONARY HEMODYNAMIC EFFECTS OF INTRAVENOUS DILTIAZEM IN PATIENTS WITH CORONARY ARTERY DISEASE Julio F. Tubau, MD; Pierre C8t6, MD, FACC; Martial G. Bourassa, MD, FACC, Montreal Heart Institute, Quebec.

The oral form of Diltiazem (D), a new calcium antagonist, seems to provide more benefit to coronary patients (pts) than the usual coronary dilators (nitroglycerin excepted). The effects of intravenous D in human are not well known. Therefore in 8 angina pts undergoing coronary arteriogra- phy, heart rate (HR), systolic blood pressure (SBP), stroke volume index @VI), systemic vascular resistance (SVR) as well as coronary sinus blood flow (CSBF) and 02 consumption by the heart (MVOZ) were measured at rest and throughout the infusion period. Two separate doses of D, 15 and 30 ug/kg/min, were administered for 10 min each with a 10 min interval in between.

Rest D 15 pg D 30 vg

HR(beats/min) (0 min) (10 min) (30 min) (45 min) ?6+2 77*2 74?3 69?3**

SBP b@) SVI(ml/beat/m*)

133i6 130*5 12126 * 122f7* 38+2 44*3 * 45*4 *

SVR(dyn.sec.cm-5) 1480+114 1336+99 1190280*** CSBF(ml/min) 142k24 158+23* 160*22X MVOZ(ml/min) 1470+269 1452+113 1300+87

% t SEM *p<.os; **p<.oz; ***p<.OOl (compared to resting values) These data show that D infused for a short neriod of time ects primarily as a peripheral and coronary vasodilator, decreasing SBP and SVR and increasing CSBF. However, 10 min after discontinuation of the drug, HR decreases sig- nificantly while SBP remains lower than at test. Therefore D reduces HR in addition to its main vasodilator effect, but the onset of its negative chronotropic action is de- layed significantly compared to afterload reduction. At this point D should induce a significant reduction in myo- cardial oxygen consumption.

EFFICACY OF DILTIAZEM IN VARIANT ANGINA Steven Rosenthal, MD; Robert Ginsburg, MD; Irene Iamb, RN; Donald Bairn. MD: John Schroeder. MD. FACC. Stanford University,-Stanford, California.

Diltiazem is a new calcium "slow channel" blocker for the treatment of variant angina. Seven patients with variant angina documented to be secondary to coronary artery spasm completed a lo-week double blind study with three L-week placebo periods and one Z-week period of Diltiazem 12Omg per day and one 2-week period of Diltiazem 240mg per day. Response was assessed by number of episodes of pain and nitroglycerin consumption. There were 596 epi- sodes of pain during 272 patient-days of placebo (2.19 per patient-day) with a significant reduction to 43 epi- sodes during 95 patient-days of Diltiazem 12Omg per day (0.45 per patient-day) (pc.05) and to 23 episodes during 93 per patient-days of Diltiazem 240mg per day (0.24 per patient-day) (pc.02). Nitroglycerin consumption was also significantly reduced from 2.01 per patient-day during placebo to 0.47 per patient-day during Diltiazem 12Omg per day (pc.04) and to 0.24 per patient-day during Diltiazem 24Omg per day (pc.03). Six of seven patients were complete or near complete responders; one of seven patients was an incomplete responder to 24Cmg per day. There were no complications or side effects. In conclu- sion, Diltiazem is an extremely effective drug in the treatment of variant angina.

February 1980 The American Journal of CARDIOLOGY Volume 45 439