Impact of the Food and Drug Administration Approval of Flecainide and Encainide on Coronary Artery Disease Mortality: Putting Deadly Medicine to the Test

In his book Deadly Medicine and on television, Thomas Moore impugns the process of antiarrhythmic drug approval in the 1980s, alleging that the new generation of drugs had flooded the marketplace and had caused deaths in numbers comparable to lives lost during war. To assess these important public health allegations, we evaluated annual coronary artery disease death rates in relation to antiarrhythmic drug sales (2 independent marketing surveys). Predicted mortality rates were modeled using linear regression analysis for 1982 through 1991. Deviations from predicted linearity were sought in relation to rising and falling class IC and overall class I antiarrhythmic drug use. Flecainide came to market in 1986 and encainide in 1987. Combined class IC sales peaked in 1987 and 1988 (maximum market penetration, 20%, first quarter 1989). Results of the Cardiac Arrhythmia Suppression Trial (CAST) were disclosed in April 1989. Overall annual class I antiarrhythmic prescription sales actually fell slightly (−3% to −4%/yr) in the 2 years before CAST and then more abruptly (−12%) in the year after CAST (1990). Sales of class IC drugs fell dramatically after CAST (by 75%). Coronary death rates (age adjusted) fell in a linear fashion during the decade of 1982 through 1991. No deviation from predicted rates was observed during the introduction, rise, and fall in class IC (and other class I) sales: rates were 126/100,000 in 1985 (before flecainide), 114 and 110 in 1987 and 1988 (maximum sales), and 103 in 1990 (after CAST). Deviations in death rates in the postulated range of 6,000 to 25,000 per year were shown to be excluded easily by the 95% confidence intervals about the predicted rates. Entry of new antiarrhythmic drugs in the 1980s did not lead to overall market expansion and had no adverse impact on coronary artery disease death rates, which fell progressively. Thus, the allegations in Deadly Medicine could not be confirmed. dly Medicine, Thomas Moore impugns the Food and Drug Administrationʹs approval of flecainide and encainide, claiming that “more than 50,000 persons died from taking antiarrhythmic drugs in a 2-year period during which patients were being enrolled in Cardiac Arrhythmia Suppression Trial (CAST).” To assess these allegations, we reviewed national coronary artery disease death statistics and found that they fell throughout the 1980s in a linear fashion, with no deviation from predicted rates during the introduction, rise, and fall of class IC (and other class I) drug sales.