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Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

The importance of short-term off-target effects in estimating the long-term renal and cardiovascular protection of angiotensin receptor blockers

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  • P A Smink
  • Y Miao
  • M J C Eijkemans
  • S J L Bakker
  • I Raz
  • H-H Parving
  • J Hoekman
  • D E Grobbee
  • D de Zeeuw
  • H J Lambers Heerspink
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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.

OriginalsprogEngelsk
TidsskriftClinical Pharmacology and Therapeutics
Vol/bind95
Udgave nummer2
Sider (fra-til)208-15
Antal sider8
ISSN0009-9236
DOI
StatusUdgivet - feb. 2014

ID: 44449595