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The relevance of subgroup-specific treatment effects: the Studies Of Left Ventricular Dysfunction (SOLVD) revisited.
Am Heart J. 2002 Dec; 144(6):941-7.AH

Abstract

BACKGROUND

The overall effect sizes estimated from randomized clinical trials may not apply similarly to all patients. Univariate subgroup analyses are often used to help determine the generalizability of a trial's results, but may themselves be misleading. We reanalyzed the Studies of Left Ventricular Dysfunction (SOLVD) to determine whether the treatment effect depended on the patients' baseline prognosis, defined on the basis of multiple clinical variables.

METHODS

The SOLVD prevention (4228 patients) and the SOLVD treatment (2569 patients) trials were randomized, double-blind trials that studied the effect of enalapril in patients with reduced left-ventricular function or congestive heart failure. We combined both SOLVD populations and compared the results of a univariate analysis to a multivariate approach in which 3 patient subgroups were defined according to baseline risks for the combined end point of death or hospitalization for heart failure.

RESULTS

Enalapril treatment resulted in 24% fewer events. The strongest predictors of an event were ejection fraction, New York Heart Association classification and age, antiplatelet agents, history of diabetes mellitus, treatment with digoxin or diuretics, and race. Only ejection fraction produced a significant treatment interaction (P =.004). Consistent with the original SOLVD reports, this interaction was also demonstrable when ejection fraction was scaled into tertiles and examined on its own (P =.012). However, there was no interaction present when patients were divided into tertiles of multifactorial baseline risk.

CONCLUSIONS

We confirmed the treatment effect of enalapril, the impact of left-ventricular systolic function, and the negative prognostic importance of diabetes mellitus in this population. Although ejection fraction led to a subgroup-treatment interaction in the main SOLVD publications, a multifactorial approach to prognostic grouping abolished the interaction. These findings highlight the limitations of univariate subgroup analyses and illustrate that multivariate risk group analysis may be a complementary method for assessing the generalizability of the overall treatment effects observed in randomized trials.

Authors+Show Affiliations

Institute of Medical Sciences, University of Toronto, and Cardiac Research Inc, Toronto, Ontario, Canada. abp.care@sympatico.caNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

12486418

Citation

Parker, Andrea B., et al. "The Relevance of Subgroup-specific Treatment Effects: the Studies of Left Ventricular Dysfunction (SOLVD) Revisited." American Heart Journal, vol. 144, no. 6, 2002, pp. 941-7.
Parker AB, Yusuf S, Naylor CD. The relevance of subgroup-specific treatment effects: the Studies Of Left Ventricular Dysfunction (SOLVD) revisited. Am Heart J. 2002;144(6):941-7.
Parker, A. B., Yusuf, S., & Naylor, C. D. (2002). The relevance of subgroup-specific treatment effects: the Studies Of Left Ventricular Dysfunction (SOLVD) revisited. American Heart Journal, 144(6), 941-7.
Parker AB, Yusuf S, Naylor CD. The Relevance of Subgroup-specific Treatment Effects: the Studies of Left Ventricular Dysfunction (SOLVD) Revisited. Am Heart J. 2002;144(6):941-7. PubMed PMID: 12486418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The relevance of subgroup-specific treatment effects: the Studies Of Left Ventricular Dysfunction (SOLVD) revisited. AU - Parker,Andrea B, AU - Yusuf,Salim, AU - Naylor,C David, PY - 2002/12/18/pubmed PY - 2003/1/17/medline PY - 2002/12/18/entrez SP - 941 EP - 7 JF - American heart journal JO - Am Heart J VL - 144 IS - 6 N2 - BACKGROUND: The overall effect sizes estimated from randomized clinical trials may not apply similarly to all patients. Univariate subgroup analyses are often used to help determine the generalizability of a trial's results, but may themselves be misleading. We reanalyzed the Studies of Left Ventricular Dysfunction (SOLVD) to determine whether the treatment effect depended on the patients' baseline prognosis, defined on the basis of multiple clinical variables. METHODS: The SOLVD prevention (4228 patients) and the SOLVD treatment (2569 patients) trials were randomized, double-blind trials that studied the effect of enalapril in patients with reduced left-ventricular function or congestive heart failure. We combined both SOLVD populations and compared the results of a univariate analysis to a multivariate approach in which 3 patient subgroups were defined according to baseline risks for the combined end point of death or hospitalization for heart failure. RESULTS: Enalapril treatment resulted in 24% fewer events. The strongest predictors of an event were ejection fraction, New York Heart Association classification and age, antiplatelet agents, history of diabetes mellitus, treatment with digoxin or diuretics, and race. Only ejection fraction produced a significant treatment interaction (P =.004). Consistent with the original SOLVD reports, this interaction was also demonstrable when ejection fraction was scaled into tertiles and examined on its own (P =.012). However, there was no interaction present when patients were divided into tertiles of multifactorial baseline risk. CONCLUSIONS: We confirmed the treatment effect of enalapril, the impact of left-ventricular systolic function, and the negative prognostic importance of diabetes mellitus in this population. Although ejection fraction led to a subgroup-treatment interaction in the main SOLVD publications, a multifactorial approach to prognostic grouping abolished the interaction. These findings highlight the limitations of univariate subgroup analyses and illustrate that multivariate risk group analysis may be a complementary method for assessing the generalizability of the overall treatment effects observed in randomized trials. SN - 1097-6744 UR - https://www.unboundmedicine.com/medline/citation/12486418/The_relevance_of_subgroup_specific_treatment_effects:_the_Studies_Of_Left_Ventricular_Dysfunction__SOLVD__revisited_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002870302002181 DB - PRIME DP - Unbound Medicine ER -