Medical treatment of myocardial ischemia in coronary artery disease: effect of drug regime and irregular dosing in the CAPE II trial.
OBJECTIVE
The Circadian Anti-ischemia Program in Europe (CAPE II) compared the efficacy of amlodipine and diltiazem (Adizem XL) and the combination of amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on exercise and ambulatory myocardial ischemia during regular therapy and after omission of medication.


BACKGROUND
The optimal medical therapy for ischemia suppression and the impact of irregular dosing using agents with different pharmacologic properties has not been established in patients with coronary disease.


METHODS
Patients with > or = 4 ischemic episodes or > or = 20 min of ST segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind randomized multicountry study. In the second phase, atenolol 100 mg was added to amlodipine and isosorbide 5-mononitrate 100 mg to diltiazem (Adizem XL). Ambulatory monitoring (72 h) and exercise testing were repeated after both phases, on treatment and after a 24-h drug-free interval.


RESULTS
Both monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms and ambulatory and exercise ischemia. Combination therapy reduced ischemia further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5-mononitrate. Amlodipine/atenolol was significantly superior during the drug-free interval with maintenance of ischemia reduction.


CONCLUSIONS
Amlodipine, with its intrinsically long half-life alone or together with beta-blocker, is likely to produce superior ischemia reduction in clinical practice when patients frequently forget to take medication or dose irregularly.
Deanfield
John E
JE
Vascular Physiology Unit, Great Ormond Street Hospital for Children, London, United Kingdom. j.deanfield@ich.ucl.ac.uk
Detry
Jean-Marie
JM
Sellier
Philippe
P
Lichtlen
Paul R
PR
Thaulow
Eric
E
Bultas
Jan
J
Brennan
Claudia
C
Young
Sarah T
ST
Beckerman
Bruce
B
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000008:administration & dosage; D001262:Atenolol / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage; D003327:Coronary Disease / Q000150:complications*; D004110:Diltiazem / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006801:Humans; D007547:Isosorbide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D017311:Amlodipine; D001262:Atenolol; D004110:Diltiazem; D007547:Isosorbide