관동맥연축에서 서방형 칼슘길항제인 Diltiazem 과 Verapamil 의 치료효과 : Ergonovine Echocardiography 를 이용한 무작위 비교 연구

Background: Detection of left ventricular regional wall motion abnormality with two dimensional echocardiography during ergonovine injection (Ergonovine Echocardiography: Erg Echo) is a useful noninvasive diagnostic method of coronary vasospasm, and as it can be used repeatedly, comparison of the therapeutic efficacy of the prescribed drugs for the patients with variant angina may be possible with this method. The purpose of this study were to compare the antispasmotic action of short-term medication of two currently available sustained-releasing (SR) calcium antagonists (Diltiazem vs Verapamil) with Erg Echo, to investigate the factors determining the drug efficacy and to determine if the results of repeated tests of Erg Echo after shortterm medication correlate with the clinical response. Methods: Forty patients with angiographicallyproven coronary vasospam and positive Erg Echo without medication were randomly assigned into group I and II. Diltiazem SR 90mg b.i,d. was prescribed in the patients of group l and Verapamil SR 120 mg b.i.d. in group II. Isosorbide-5-mononitrate (ISMN, Elantan 20 mg b.i.d.) was commonly given in both groups. After medication of 4 days Erg Echo was repeated, and if follow up results were positive doubling of the dosage of prescribed calcium channel antagonists (i.e. Diltiazem SR 180 mg or Verapamil SR 240 mg b.i.d.) was done and the second follow up test of Erg Echo was performed after another 4 days. Clinical follow-up was done with the dosage of negative Erg Echo, and during 9 (±3) month follow-up period one patient of group I and two of group II were lost and final analysis was done with total 37 patients (19 in group I and 18 in group II). Results: Among 37 patients with variant angina, 32 were male and the mean age was 53 (±8). Sex ratio, mean age, body weight, clinical activity of variant angina assessed by the frquency of chest pain attack, number of spasm-documented coronary vessels, dosage of ergonovine for positive response in baseline Erg Echo and number of the patients with concomitant fixed coronary stenosis were not significantly different between both groups. After 4 day medication coronary vasospasm was not provoked with ergonovine injection in 13 patients of group I, and the positive rate of Erg Echo after medication was 32% (6/19) in group I, which was not significantly different from that (50%, 9/18) of group II (p=0.66). In 15 patients coronary vasospasm was provoked with ergonovine injection despite the medication, and ergonovine dose for positive response rose from 146±84 microgram (mcg) to 218±75 mcg with medication. Patients with 'mixed disease' (coronary vasospasm and concomitant fixed disease) showed higher positive result of Erg Echo after medication than the patients with pure spasm (p=0.001). During open label follow-up of 9±3 months, there was neither case of acute myocardial infarction nor that of sudden cardiac death. Recurrent chest pain with medication was observed in 6 patients of group I and 7 of group II (p=0.90), and recurrent chest pain during follow-up was more frequently observed in patients with positive Erg Echo after 4 day medication than those with negative test (p=0.01). In group II medication was modified to control the high activity of variant angina (chest pain attacks more than 5 per week) in 3 patients and verapamil SR was withdrawned in 4 patients due to side effects (2 cases of impotence, each case of constipation and peripheral edema), while there was no case of drug modification or withdrawl of diltiazem SR (p<0.05) in group I. Conclusion: Although there was no significant difference of short term medication on prevention of coronary vasospasm provoked by ergonovine injection, during long term follow-up of variant angina, diltizem SR with ISMN was superior to verapamil SR with ISMN in control of chest pain and absence of side effects. Erg Echo after short term medication was useful in comparison of drug efficacy, investication of the fact