Efficacy of diltiazem in variant angina. Results of a double-blind crossover study in CCU by Holter monitoring. The possible occurrence of a withdrawal syndrome.Pesola A, Lauro A, Gallo R, Madeo A, Cosentino G. G Ital Cardiol 1987 Apr;17(4):329-39.

Abstract : The short and long term efficacy of diltiazem, a calcium-entry blocker, has been evaluated in a group of ten patients with Prinzmetal's variant
angina admitted to a CCU. In the short term part of the study, after a run-in period, diltiazem 60 mg tid and placebo were administered
alternatively during 4 randomized 72 hour periods. Response was assessed using continuous Holter monitoring, measuring the frequency of
transient ischemic attacks. During the run-in period the number of episodes/day/patient was 16.1. No episodes of transient ST segment
elevation were recorded during both periods of diltiazem treatment in 3 patients and during one of the two periods in 4. For the group as a
whole the number of episodes during the first placebo period was not statistically different from that during the run-in period (208 versus 161).
No statistically significant difference was also found in 8 patients comparing the number of episodes during the second placebo period and the
run-in period (166 versus 101). During each period of diltiazem treatment an highly significant reduction in the number of episodes was
observed (43 and 5, p = .006 and p = .02). Two patients did not complete the study protocol. Both patients had a worsening of angina during the
first placebo period following diltiazem treatment. One of them developed an acute myocardial infarction. The possible occurrence of a rebound
phenomenon after withdrawal of diltiazem seems to be indicated, in 6 patients, by a significant increase in the number of ischemic episodes
recorded during the placebo period following active treatment in respect to the number during the first placebo period (159 versus 73, p =