Suppressing premature ventricular beats after a heart attack reduces the risk of sudden death.

After a heart attack, some patients have frequent premature ventricular beats.

These are extra heartbeats that begin in the ventricles, the heart’s main pumping chambers, before the next normal beat is due. Because frequent abnormal beats were associated with a higher risk of sudden cardiac death, they seemed like more than a warning sign: perhaps they were part of the cause.

That made the treatment logic straightforward. If a drug suppressed the premature beats, it should reduce dangerous arrhythmias and save lives.

The drugs encainide and flecainide worked well on the electrical marker. Patients’ electrocardiograms, or ECGs, showed far fewer premature ventricular beats.

The Cardiac Arrhythmia Suppression Trial, known as CAST, asked the more important question: did those patients actually live longer?

They did not. Patients receiving the active drugs had more deaths from arrhythmias and higher overall mortality than those receiving placebo. The relevant treatment arms were stopped early.

The premature beats were a surrogate endpoint—a measurable sign associated with the real outcome of interest. CAST became a classic demonstration that improving such a marker does not prove that a treatment improves health.

The trial does not mean every antiarrhythmic drug is dangerous in every setting. Its lesson was specific and powerful: in high-risk patients after myocardial infarction, suppressing ventricular ectopy with these drugs made the ECG look better while making survival worse.