To determine the frequency of rebound anginal symptoms on abrupt withdrawal of
calcium channel blocking agents, anginal symptoms were retrospectively examined in patients with
Prinzmetal's variant angina abruptly withdrawn from
diltiazem therapy as part of the design of a placebo-controlled multiple crossover trial. Rebound was defined as a return of anginal symptoms to levels exceeding those of the pretreatment baseline state. Values for daily frequency of angina were compared (after subtracting corresponding baseline values) between placebo periods following
diltiazem periods and placebo periods following placebo periods. No intergroup differences existed between mean changes in daily frequency of angina from baseline value (-0.61 for placebo following
diltiazem versus -1.10 for placebo following placebo) (p greater than 0.4). Furthermore, in 13 (28%) of 46 occurrences when placebo followed placebo, daily frequency of angina exceeded baseline value in the immediate 3 day period following placebo compared with 17 (21%) of 80 occurrences when placebo followed
diltiazem. There was no increased rebound occurrence comparing high dose (240 mg/day) with low dose (120 mg/day)
diltiazem therapy. No significant symptoms such as
myocardial infarction or
unstable angina occurred after withdrawal of
diltiazem or placebo. The lack of difference in rebound after
diltiazem or placebo withdrawal was consistent using paired and unpaired analyses. In conclusion, there appears to be no evidence that abrupt withdrawal of
therapy with
diltiazem results in rebound anginal symptoms.