Mitchell et al., "Mortality and morbidity in patients receiving encainide
, flecainide, or placebo--the Cardiac Arrhythmia Suppression Trial," The New England Journal of Medicine, vol.
Investigators, Preliminary Report: Effect of Encainide
and Flecainide on
One frequently cited case involves the anti-arrhythmia drugs encainide
In the US, dogs failed to predict heart problems caused by the cardiovascular drugs encainide
and flecainide which led to an estimated 3,000 deaths.
Among the drugs of particular importance in this regard are those with a narrow therapeutic index including flecainide, encainide
, vinblastine, carbamazepine, and TCAs.
The trial was halted because it clearly showed that the three sodium channel blockers being studied (encainide
, flecainide, and morizicine) increased mortality--even though they had effectively corrected the arrhythmia.
Nonetheless, on October 31, 1985 - only three months later - FDA approved Tambocor for patients with less severe as well as life-threatening arrhythmias.(35) After approval, clinical trials sponsored by the National Heart, Lung, and Blood Institute revealed a two-and-a-half-fold increase in mortality among patients treated with Tambocor or Enkaid (encainide
HCl) - another antiarrthythmic agent - compared to patients receiving a placebo.
Recently, the Cardiac Arrhythmia Suppression Trial showed that the Class Ic drugs flecainide and encainide
increased mortality by two and a half times compared with placebo in patients who were enrolled 6 days to 2 years after myocardial infarction and had six or more ventricular ectopics per hour, with no sustained ventricular tachycardia[6, 7].
Drugs which could be affected by poor metabolism include metoprolol, a 13-blocker, and recently Encainide
, scheme 5, a potent drug which suppresses irregular heart beats and which has been examined in patients by Laganiere in collaboration with the Ottawa Heart Institute and other North American centres.
Study patients taking encainide
(marketed as Enkaid by Bristol Laboratories in Evansville, Ind.) and flecainide (marketed as Tambocor by 3M Riker in St.
(12) Similarly, encainide
and flecainide reduce the incidence of arrhythmias after acute myocardial infarction, but they also increase mortality.
Increased risk of death and cardiac arrest from encainide
and flecainide in patients after non-Q-wave acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial.
Mortality in patients treated with flecainide and encainide
for supraventricular arrhythmias.
was provided by Bristol-Myers, Princeton, NJ.
The widespread use of encainide
and flecainide before POEMs were available led to more than 50,000 premature deaths, more than all the Americans killed during the Vietnam War.