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Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial.

AbstractBACKGROUND:
Mibefradil is a T-type calcium-channel antagonist and arterial vasodilator with negative chronotropic effects. It is not known if T-type calcium-channel blockade is superior to L-type calcium-channel blockade in patients with stable angina pectoris.
METHODS:
A multicenter, randomized, double-blind trial was conducted in patients with documented coronary disease and stable angina to compare a 360 mg dose of diltiazem CD with 100 mg dose of mibefradil. The primary end point was change in time to symptom-limited exercise termination from baseline to 8 weeks. Secondary efficacy parameters included time to onset of persistent ST-segment depression, time to awareness of angina, and change in exercise duration from baseline to 2 and 4 weeks of treatment.
RESULTS:
A total of 121 patients were randomized to mibefradil and 113 to diltiazem CD. At 8 weeks, the increase in exercise duration was 24.5 seconds greater in the mibefradil group (P =.017; 95% CI 4.4-44.7 seconds). At 8 weeks, time to development of > or =1 mm ST-segment depression was greater by 45.3 seconds (P =.0025; 95% CI 16.2-74.5) with mibefradil, but time to development of angina was not significantly different.
CONCLUSION:
T-type calcium-channel antagonism with mibefradil improved treadmill exercise parameters compared with diltiazem in patients with chronic stable angina. Further investigation and development of antagonists of T-type calcium channels with fewer adverse drug interactions is warranted and may be promising in the management of ischemic heart disease.
AuthorsDouglas S Lee, Shaun Goodman, Deanne M Dean, Jacques Lenis, Patrick Ma, Pierre B Gervais, Anatoly Langer, PRIDE Investigators
JournalAmerican heart journal (Am Heart J) Vol. 144 Issue 1 Pg. 60-7 (Jul 2002) ISSN: 1097-6744 [Electronic] United States
PMID12094189 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Calcium Channels, T-Type
  • Mibefradil
  • Diltiazem
Topics
  • Angina Pectoris (drug therapy)
  • Calcium Channel Blockers (therapeutic use)
  • Calcium Channels, L-Type
  • Calcium Channels, T-Type
  • Diltiazem (therapeutic use)
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mibefradil (therapeutic use)
  • Middle Aged
  • Myocardial Ischemia (drug therapy)

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