Spanish Study on Sudden Death - SSSD


SSSD was a randomized, placebo-controlled trial of amiodarone versus metoprolol for prevention of ventricular ectopy and mortality in post-MI patients with LV dysfunction.


Amiodarone and metoprolol will reduce ventricular ectopy and improve mortality in post-MI patients with reduced LV function.

Study Design

Study Design:

Patients Enrolled: 368
Mean Follow Up: 3 years
Mean Patient Age: <75

Patient Populations:

Men and women less than 75 years old, 10 to 60 days after myocardial infarction with (1) ejection fraction 20 to 45%, (2) an average of >/= 3 VPCs per hour, couplets or runs of <15 bears, in at least 1 of two 24 hour holter recordings.


Malignant ventricular arrhythmias, symptomatic bradycardia, sinus node dysfunction, pauses >3 seconds, AV block (PR>0.24s), QRS >0.14s, long QT (>0.55s), NYHA Class III or IV, hypotension, bronchial asthma, thyroid disease, other contraindications to beta blockers or amiodarone.

Primary Endpoints:

Mortality at 3 years.

Secondary Endpoints:

Rates of VPCs on holter monitoring.

Drug/Procedures Used:

Patients were enrolled 10 to 60 days after acute myocardial infarction and randomly assigned to either placebo, metoprolol (50 to 100mg bid), or amiodarone (200mg qd after two week loading period). Holter monitoring occurred at 1, 6, and 12 months.

Concomitant Medications:

Patients on antiarrhythmic drugs at enrollment underwent a washout period. Other medications such as aspirin, captopril, and digoxin were allowed.

Principal Findings:

SSSD randomized 368 patients to three arms: placebo (n=123), metoprolol (n=130), and amiodarone (n=115). Patients were randomized a median of 37 days post MI. At baseline the groups were well matched in terms of age, gender, comorbidities, ejection fraction, and concomitant medications.

After a median follow up of 33.4 months there were a total of 30 deaths. Mortality for the amiodarone arm did not differ from the placebo group (3.5% vs. 7.7%, p=0.19) but was lower than the metoprolol group (15.4%, p<0.006 for comparison to amiodarone). The mortality rate for the beta blocker arm was twice that of placebo although the difference was not statistically significant (p=0.14).

Amiodarone was effective in reducing overall frequency of VPCs by >50%. In contrast, frequency of VPCs in the metoprolol arm was similar to placebo (26/hr vs. 24/hr).


Among post-MI patients with reduced ejection fraction, amiodarone therapy was associated with lower mortality over standard beta blocker therapy. This finding is controversial, however, and not supported by several other trials. The authors suggest that their results may be due to chance, given the small number of patients and low event rate. Although amiodarone improved survival over metoprolol, it did not outperform placebo, making the findings questionable.


Navarro-Lopez F, Cosin J, Marrugat J, Guindo J, Bayes de Luna A, Comparison of the effects of amiodarone versus metoprolol on the frequency of ventricular arrhythmias and on mortality after acute myocardial infarction. SSSD Investigators. Spanish Study on Sudden Death. Am J Cardiol. 1993 Dec 1;72(17):1243-8

Clinical Topics: Arrhythmias and Clinical EP, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Myocardial Infarction, Follow-Up Studies, Comorbidity, Electrocardiography, Ambulatory, Metoprolol

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