Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT TrialReportar como inadecuado




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Cardiovascular Drugs and Therapy

pp 1–13

Differential Response in Acute Heart FailureFirst Online: 27 June 2017

Abstract

BackgroundOver the last 50 years, clinical trials of novel interventions for acute heart failure AHF have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.

MethodsWe studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.

ResultsIn the overall study population, rolofylline had no effect on mortality HR 1.03, 95% CI 0.82–1.28, p = 0.808. We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 WAP-4C, and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol, treatment with rolofylline was beneficial HR 0.61, 95% CI 0.40–0.92, p = 0.019. In patients with score 0, treatment with rolofylline was harmful HR 5.52, 95% CI 1.68–18.13, p = 0.005; treatment by score interaction p < 0.001. Internal validation estimated similar hazard ratio estimates 0 points: HR 5.56, 95% CI 5.27–7–5.87; 1 point: HR 1.31, 95% CI 1.25–1.33; 2 points: HR 0.75, 95% CI 0.74–0.76; 3 points: HR 1.13, 95% CI 1.11–1.15; 4 points, HR 0.61, 95% CI 0.61–0.62 compared to the original data.

ConclusionBiomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.

KeywordsAcute heart failure Treatment heterogeneity Biomarkers Subpopulation treatment effect pattern plot Rolofylline Electronic supplementary materialThe online version of this article doi:10.1007-s10557-017-6726-1 contains supplementary material, which is available to authorized users.

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Autor: Licette C. Y. Liu - Mattia A. E. Valente - Douwe Postmus - Christopher M. O’Connor - Marco Metra - Howard C. Dittric

Fuente: https://link.springer.com/







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