The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) observational follow-up study: benefits of RAS blockade with olmesartan treatment are sustained after study discontinuation

Jan Menne, Eberhard Ritz, Luis M Ruilope, Christos Chatzikyrkou, Giancarlo Viberti, Hermann Haller, Jan Menne, Eberhard Ritz, Luis M Ruilope, Christos Chatzikyrkou, Giancarlo Viberti, Hermann Haller

Abstract

Background: The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study showed that 40 mg Olmesartan medoxomil (OM) versus placebo delayed microalbuminuria onset in patients with type 2 diabetes and normoalbuminuria.

Methods and results: One thousand seven hundred and fifty-eight ROADMAP patients (placebo arm: 877; OM arm: 881) participated in the observational follow up (OFU) with an average of 3.3 years. They received standard medical care and micro- and macrovascular events were documented. During observational follow-up 62.9% and 60.1% in the former OM and placebo group, respectively, received treatment with a RAS blocking agent. During the OFU period the systolic blood pressure (SBP) increased to mean values of 135 mm Hg in both groups. Patients who had developed microalbuminuria during ROADMAP had a higher incidence of cardio- and cerebrovascular events (OR 1.77, CI 1.03 to 3.03, P=0.039) during the OFU period compared with patients in whom this was not the case. Diabetic retinopathy was significantly reduced in the former OM group (8 [0.9%] versus 23 [2.6%], OR: 0.34, CI 0.15 to 0.78, P=0.011) and the rate of microalbuminuria was numerically reduced. Congestive heart failure requiring hospitalization (3 [0.3%] versus 12 [1.4%], OR: 0.23, CI 0.06 to 0.85, P=0.027) was reduced and there was a trend of reduced cardio-/cerebrovascular events (OM versus Pb: 73 [8.3%] versus 86 [9.8%] patients). Seven (0.8%) deaths (including 2 CV events) were reported in former placebo patients versus 3 (0.3%) (non-CV events) in former OM patients.

Conclusions: Development of microalbuminuria is a valid marker for future CV events. RAS blockade with Olmesartan might cause sustained reduction (legacy effect) of micro- and macrovascular events.

Trial registration: ClinicalTrials.gov NCT00185159.

Figures

Figure 1.
Figure 1.
Blood pressure control per former ROADMAP treatment group. A, systolic (SBP) and diastolic (DBP) blood pressure; (B) BP goal P<0.001. OFU indicates observational follow up; ROADMAP, Randomized Olmesartan and Diabetes Microalbuminuria Prevention.
Figure 2.
Figure 2.
HbA1c control during ROADMAP‐OFU. OFU indicates observational follow up; ROADMAP, Randomized Olmesartan and Diabetes Microalbuminuria Prevention.
Figure 3.
Figure 3.
Presence of microalbuminuria during the ROADMAP‐OFU trial by former ROADMAP treatment groups. Four different counting rules were applied to identify patients with microalbuminuria. *P<0.05. OFU indicates observational follow up; ROADMAP, Randomized Olmesartan and Diabetes Microalbuminuria Prevention.
Figure 4.
Figure 4.
Presence of microalbuminuria in patients without microalbuminuria during the ROADMAP trial by former ROADMAP treatment groups. Four different counting rules were applied to identify patients with microalbuminuria. OFU indicates observational follow up; ROADMAP, Randomized Olmesartan and Diabetes Microalbuminuria Prevention.
Figure 5.
Figure 5.
eGFR per former ROADMAP treatment group. ***P<0.001. eGFR indicates estimated glomerular filtration rate; OFU, observational follow up; ROADMAP, Randomized Olmesartan and Diabetes Microalbuminuria Prevention.
Figure 6.
Figure 6.
Change in eGFR (mean±SEM) per former ROADMAP treatment group and RAS blockade during OFU period. eGFR indicates estimated glomerular filtration rate; OFU, observational follow up; RAS, renin‐angiotensin‐system; ROADMAP, Randomized Olmesartan and Diabetes Microalbuminuria Prevention.

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