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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blocking agents, anginal symptoms were retrospectively examined in patients with Prinzmetal's variant angina abruptly withdrawn from diltiazem therapy as part of the design of a placebo-controlled multiple crossover trial.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>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.