The Importance of Short-Term Off-Target Effects in Estimating the Long-Term Renal and Cardiovascular Protection of Angiotensin Receptor Blockers

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

Research output: Contribution to journalArticleAcademicpeer-review

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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 (RRRpredicted: 30.1% vs. RRRobserved: 213%; P = 0.44) and cardiovascular outcomes (RRRpredicted: 9.4% vs. RRRobserved: 92%; 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.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalClinical Pharmacology & Therapeutics
Volume95
Issue number2
DOIs
Publication statusPublished - Feb-2014

Keywords

  • DIABETIC-NEPHROPATHY
  • BLOOD-PRESSURE
  • HIGH-RISK
  • END-POINTS
  • LOSARTAN
  • TRIAL
  • OUTCOMES
  • DISEASE
  • HYPERTENSION
  • TELMISARTAN

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