The importance of short-term off-target effects in estimating the long-term renal and cardiovascular protection of angiotensin receptor blockers.
Clin Pharmacol Ther
; 95(2): 208-15, 2014 Feb.
Article
de En
| MEDLINE
| ID: mdl-24067744
ABSTRACT
Angiotensin receptor blockers (ARBs) have multiple effects that may contribute to their efficacy on renal/cardiovascular outcomes. We developed and validated a risk score that incorporated short-term changes in multiple risk markers to predict the ARB effect on renal/cardiovascular outcomes. The score was used to predict renal/cardiovascular risk at baseline and at month 6 in the ARB treatment arm of the Reduction of Endpoints in NIDDM (noninsulin-dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL) trial. The net risk difference at these time points indicated the estimated long-term renal/cardiovascular treatment effect. Predicted relative risk reductions (RRRs) based on multiple markers were close to observed RRRs for renal (RRR(predicted) 30.1% vs. RRR(observed) 21.8%; P = 0.44) and cardiovascular outcomes (RRR(predicted) 9.4% vs. RRR(observed) 9.2%; P = 0.98), in addition to being markedly more accurate than predicted RRRs based on changes in single markers. The score was validated in an independent ARB trial. Predictions of long-term renal/cardiovascular ARB effects are more accurate when considering short-term changes in multiple risk markers, challenging the use of single markers to establish drug efficacy.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladies cardiovasculaires
/
Antagonistes des récepteurs aux angiotensines
/
Maladies du rein
Type d'étude:
Etiology_studies
/
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Clin Pharmacol Ther
Année:
2014
Type de document:
Article
Pays d'affiliation:
Pays-Bas