Long-Term Survival Effect of Metoprolol in Dilated Cardiomyopathy - SPIC

Description:

SPIC was a prospective multicenter registry used to determine the survival effect of metoprolol versus standard treatment in patients with idiopathic dilated cardiomyopathy.

Hypothesis:

Metoprolol added to standard treatment for idiopathic dilated cardiomyopathy would be associated with improved survival.

Study Design

Study Design:

Patients Enrolled: 586
Mean Follow Up: Mean 52 months
Mean Patient Age: 44 ± 12
Female: 25

Patient Populations:

Left ventricular ejection fraction ≤50%, absence of significant (>50%) coronary artery stenoses, and exclusion of specific heart muscle disease or active myocarditis by endomyocardial biopsy

Exclusions:

None

Primary Endpoints:

All-cause mortality

Secondary Endpoints:

Heart transplant

Drug/Procedures Used:

The registry enrolled patients with idiopathic dilated cardiomyopathy. This study evaluated a subset of 175 patients with substantial left ventricular dysfunction (<40%) or a history of symptomatic heart failure or both that were additionally treated with metoprolol titrated to the maximum tolerated dose (goal HR <60). These patients were compared to a matched control group treated with standard therapy.

Concomitant Medications:

For the entire registry, angiotensin-converting enzyme (ACE) inhibitors in 82%, digitalis in 75%, furosemide in 53%, and amiodarone in 40%

Principal Findings:

The registry enrolled 586 consecutive patients. Of these patients, 175 were treated with metoprolol from enrollment onward. The average tolerated dose was 117 mg. The conventional treatment cohort consisted of the remaining 411 subjects. Analysis was done by use of metoprolol or not at enrollment; 75 patients in the conventional cohort received metoprolol at some point after enrollment.

At enrollment, the cohorts were similar in terms of age, blood pressure, and New York Heart Association class. The metoprolol cohort had a lower prevalence of atrial fibrillation, lower mean aortic and filling pressures, a higher frequency of borderline hypertension, and a higher cardiac index. This group also was more often treated with digitalis and ACE inhibitors and less often with furosemide and amiodarone.

Over a mean follow-up of 52 months, the metoprolol cohort had significantly higher two-year survival (96% vs. 87%, p=0.003) and seven-year survival (81% vs. 60%, p<0.001) than the conventional cohort. In a Cox multivariate model, metoprolol was associated with lower all-cause mortality with a relative risk reduction of 51% (95% confidence interval -21 to -69%, p=0.002).

A second analysis was performed comparing 127 metoprolol cases to matched controls. Survival rates were higher for the metoprolol patients at two years (97% vs. 89%, p=0.017), five years (84% vs. 72%, p=0.0079), and seven years (80% vs. 62%, p=0.036).

Interpretation:

Among patients with idiopathic dilated cardiomyopathy, use of metoprolol added to standard heart failure treatment was associated with improved long-term survival in this registry study. However, given the nonrandomized, registry nature of the study, limited conclusions can be drawn.

References:

Di Lenarda A, De Maria R, Gavazzi A, et al. Long-term survival effect of metoprolol in dilated cardiomyopathy. The SPIC (Italian Multicentre Cardiomyopathy Study) Group. Heart 1998;79:337-44.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Statins, Acute Heart Failure, Hypertension

Keywords: Risk, Follow-Up Studies, Biopsy, Digitalis Glycosides, Myocarditis, Blood Pressure, Myocardium, Furosemide, Coronary Stenosis, Survival Rate, Heart Failure, Stroke Volume, Maximum Tolerated Dose, Confidence Intervals, Metoprolol, Ventricular Dysfunction, Left, Hypertension, Cardiomyopathy, Dilated


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