Electrocardiographic effects of probucol. A controlled prospective clinical trial

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Abstract
Probucol is known to prolong QT intervals in some patients and to produce fatal arrhythmias in selected animal species. To assess the prevalence and clinical relevance of this effect in a controlled manner, we analyzed electrocardiograms (ECGs) and medical events in patients during a placebo-controlled crossover trial comparing single or combined administration of probucol and colestipol. Forty-two Type II hyperlipoproteinemic patients were studied for eighteen to twenty-four months. Two cardiologists independently read the tracings which were previously arranged randomly without names or dates. There were no statistical differences between the reports of the ECG parameters by the two cardiologists. The mean QTc interval of the entire patient population was lengthened after probucol administration without reaching statistical significance when compared to placebos or colestipol treatments. Forty-eight % of the patients showed lengthening of the QTc interval during probucol treatment by 11 to 70 msec increment over baseline placebo. The remaining had either no change or shortening of the interval. There were no statistically significant differences in means of R-R, PR, QRS, QTc or QoT intervals among placebo, probucol., colestipol and probucol plus colestipol treatments. It is concluded that probucol prolonged QT intervals in the electrocardiograms of about one half of patients receiving the drug with no other clinical or statistically significant evidence of cardiotoxicity or electrocardiographic effects.