An angiotensin II receptor blocker-calcium channel blocker combination prevents cardiovascular events in elderly high-risk hypertensive patients with chronic kidney disease better than high-dose angiotensin II receptor blockade alone

Abstract

The OSCAR study was a multicenter, prospective randomized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker (ARB) uptitration to an ARB plus calcium channel blocker (CCB) combination. In this prospective study, we performed prespecified subgroup analysis according to baseline estimated glomerular filtration rate (eGFR) with chronic kidney disease (CKD) defined as an eGFR <60 ml/min per 1.73 m(2). Blood pressure was lower in the combined therapy than in the high-dose ARB cohort in both groups with and without CKD. In patients with CKD, significantly more primary events (a composite of cardiovascular events and noncardiovascular death) occurred in the high-dose ARB group than in the combination group (30 vs. 16, respectively, hazard ratio 2.25). Significantly more cerebrovascular and more heart failure events occurred in the high-dose ARB group than in the combination group. In patients without CKD, however, the incidence of primary events was similar between the two treatments. The treatment-by-subgroup interaction was significant. Allocation to the high-dose ARB was a significant independent prognostic factor for primary events in patients with CKD. Thus, the ARB plus CCB combination conferred greater benefit in prevention of cardiovascular events in patients with CKD compared with high-dose ARB alone. Our findings provide new insight into the antihypertensive strategy for elderly hypertensive patients with CKD.

Trial registration: ClinicalTrials.gov NCT00134160.

Figure 1

Time course of systolic and diastolic blood pressure (BP) in high-dose angiotensin II receptor blocker (ARB) and ARB plus calcium channel blocker (CCB) combination groups in patients with chronic kidney disease (CKD) and without CKD. (a) Indicates patients with CKD and (b) indicates patients without CKD.

Figure 2

Kaplan–Meier curves for primary composite end points during the follow-up period in patients with chronic kidney disease (CKD) and without CKD. In (a), the number of patients in high-dose angiotensin II receptor blocker (ARB) and ARB plus calcium channel blocker (CCB) combination groups were 181 and 172, respectively, and there were 30 and 16 primary end points in high-dose ARB and ARB plus CCB combination groups, respectively. In (b), the number of primary end points was 27 in 354 patients assigned high-dose ARB and 32 in 371 patients assigned ARB plus CCB combination. CI, confidence interval; HR, hazard ratio.

Figure 3

Hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary composite end points and secondary end points in patients with chronic kidney disease (CKD) and patients without CKD at baseline. (a) Indicates patients with CKD and (b) indicates patients without CKD. The HRs and 95% CIs were derived from a stratified Cox proportional hazards model, taking into account sex, age, and baseline cardiovascular disease and type 2 diabetes. The P-values were derived from a log-rank test, stratified by sex, age, and baseline cardiovascular disease and type 2 diabetes. ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; CV, cardiovascular.

Figure 4

Time course of changes in estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD) and without CKD during the follow-up period. (a) Indicates patients with CKD and (b) indicates patients without CKD. ARB, angiotensin II receptor blocker; CCB, calcium channel blocker. Data represent the mean±s.d.

Figure 5

Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of achieved systolic blood pressure (BP) and diastolic BP levels for incidence of primary composite end points in total patients with available estimated glomerular filtration rate data (n=1078). The achieved BP on a per-patient basis was defined as the mean value of all BP values during the follow-up period. The reference category was (a) <130 mm Hg for systolic BP and (b) <70 mm Hg for diastolic BP. DBP, diastolic BP; SBP, systolic BP.