The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II

Department of Medicine, University of Washington, Seattle.

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed to test the hypothesis that suppression of ventricular premature complexes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes with encainide and flecainide worsened survival, and the CAST continued as the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fraction was lowered to less than or equal to 0.40; a higher dose of moricizine could be used; early titration itself was double-blind with a placebo, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. The Cardiac Arrhythmia Suppression Trial-II was subsequently terminated prematurely because 1) patients treated with moricizine had an excessive cardiac mortality rate during the 1st 2 weeks of exposure to the drug, and 2) there appeared to be little chance of showing a long-term survival benefit from treatment with moricizine. This report outlines the rationale behind the Cardiac Arrhythmia Suppression Trial and the reasons for selection of the drugs used in the CAST and CAST-II.

This article has been cited by other articles:

				M. R. Holcomb, M. C. Woods, I. Uzelac, J. P. Wikswo, J. M. Gilligan, and V. Y. Sidorov The Potential of Dual Camera Systems for Multimodal Imaging of Cardiac Electrophysiology and Metabolism Experimental Biology and Medicine, November 1, 2009; 234(11): 1355 - 1373. [Abstract] [Full Text] [PDF]

				S. P. Glasser and G. Howard Clinical trial design issues: at least 10 things you should look for in clinical trials. J. Clin. Pharmacol., October 1, 2006; 46(10): 1106 - 1115. [Abstract] [Full Text] [PDF]

				J. S. March, S. G. Silva, S. Compton, M. Shapiro, R. Califf, and R. Krishnan The Case for Practical Clinical Trials in Psychiatry Am J Psychiatry, May 1, 2005; 162(5): 836 - 846. [Abstract] [Full Text] [PDF]

				A H Morris Decision support and safety of clinical environments Qual. Saf. Health Care, March 1, 2002; 11(1): 69 - 75. [Abstract] [Full Text] [PDF]

				F. Di Maio, V. Rizzo, S. V. Campbell, F. Petretto, A. Corbellini, A. Bianchi, G. Bianco, F. Meloni, V. Bernardo, and D. Tallarico Effects of Cardiac Rehabilitation on Atrial Wave in Patients After Myocardial Infarction Angiology, December 1, 2001; 52(12): 827 - 833. [Abstract] [PDF]

				B. Darpo Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K70 - K80. [Abstract] [PDF]

				S. Ranger and S. Nattel Determinants and Mechanisms of Flecainide-Induced Promotion of Ventricular Tachycardia in Anesthetized Dogs Circulation, September 1, 1995; 92(5): 1300 - 1311. [Abstract] [Full Text]

				S. Goldstein, M. M. Brooks, R. Ledingham, H. L. Kennedy, A. E. Epstein, Y. Pawitan, and J. T. Bigger Association Between Ease of Suppression of Ventricular Arrhythmia and Survival Circulation, January 1, 1995; 91(1): 79 - 83. [Abstract] [Full Text]

				D. M. Roden Risks and Benefits of Antiarrhythmic Therapy N. Engl. J. Med., September 22, 1994; 331(12): 785 - 791. [Full Text]

				A. E. Epstein, A. P. Hallstrom, W. J. Rogers, P. R. Liebson, A. A. Seals, J. L. Anderson, J. D. Cohen, R. J. Capone, D. G. Wyse, and the CAST Investigators Mortality Following Ventricular Arrhythmia Suppression by Encainide, Flecainide, and Moricizine After Myocardial Infarction: The Original Design Concept of the Cardiac Arrhythmia Suppression Trial (CAST) JAMA, November 24, 1993; 270(20): 2451 - 2455. [Abstract] [PDF]

				P. C. Deedwania and E. V. Carbajal Secondary Prevention After Myocardial Infarction: Too Many Choices, Which Ones Work? Arch Intern Med, February 8, 1993; 153(3): 285 - 288. [Abstract] [PDF]