Smink, P A2; Miao, Y2; Eijkemans, M J C3; Bakker, S J L2; Raz, I4; Parving, H-H1; Hoekman, J2; Grobbee, D E5; de Zeeuw, D2; Lambers Heerspink, H J2
1 Endocrinology, Department of, Abdominal Centre, Rigshospitalet, The Capital Region of Denmark2 Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.3 Julius Center for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.4 Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel.5 Julius Center for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
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.
Clinical Pharmacology and Therapeutics, 2014, Vol 95, Issue 2, p. 208-15