Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study.
The effects of orally administered diltiazem combined with maximally tolerated doses of beta-blockers and nitrates were assessed in 12 patients, who during stress testing exhibited persistent effort angina and continued objective evidence for inducible myocardial ischemia. Patients performed multistage semisupine exercise on a bicycle ergometer during equilibrium-gated radionuclide angiography after consecutive 2 week treatment periods of placebo or diltiazem 90 mg qid (mean dose 340 mg/day) combined with maximally tolerated propranolol (mean dose 178 mg/day) and isosorbide dinitrate (mean dose 137 mg/day). All medications (including diltiazem or placebo) were administered four times daily for the duration of the study. Diltiazem or placebo was administered according to a double-blind design, with randomized cross-over at the end of each 2 week treatment period. The average number of angina attacks decreased during the double-blind cross-over phase of the trial (7 +/- 7 episodes/week at baseline vs 4 +/- 3 on placebo vs 2 +/- 2 on diltiazem; p = .08). Angina pectoris was abolished during peak exercise in eight of 12 patients on diltiazem (p less than .05 vs placebo). Diltiazem increased total exercise duration from 276 +/- 92 to 310 +/- 78 sec (p less than .005 vs baseline). Diltiazem likewise increased the time to onset of angina from 231 +/- 84 sec at baseline to 305 +/- 77 sec (p less than .005), as well as the time to the onset of 1 mm ischemic ST segment depression (p = .01). Diltiazem decreased heart rate at rest, during submaximal workload, and at peak exercise (p less than .05), and decreased systolic blood pressure at peak exercise only (p less than .05). A significant decline in rate-pressure product at submaximal and peak exercise was noted (p less than .05). At any given workload there was significantly less ST segment depression during submaximal (p = .05) and peak exercise (p less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)
Boden
W E
WE
Bough
E W
EW
Reichman
M J
MJ
Rich
V B
VB
Young
P M
PM
Korr
K S
KS
Shulman
R S
RS
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001552:Benzazepines / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy; D004110:Diltiazem / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D009566:Nitrates; D004110:Diltiazem