Shinsuke Harasawa

Renoprotective effect and cost-effectiveness of using benidipine, a calcium channel blocker, to lower the dose of angiotensin receptor blocker in hypertensive patients with albumiuria

In hypertensive patients with chronic renal disease, angiotensin receptor blockers (ARBs) are among the first-line drugs, and calcium channel blockers (CCBs) are recommended as a second line. We examined the effects of two therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP), urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned randomly to two groups. In Group A (n=14), the ARB dose was maximized and then benidipine was added until BP targets were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first and then the ARB dose was increased until BP targets were reached. The BP targets were achieved by ARB alone in 36% of Group A patients and by the addition of benidipine in 83% of Group B patients. Finally, BP decreased in each group, reaching the targets in 93% of Group A patients and 94% of Group B patients after a 4-month therapeutic period. UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period (−33±6% in Group A, −31±6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426±880 vs. 8,955±410 yen, p=0.012) and the cost-effectiveness of antihypertensive treatment was lower (p=0.003) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is, in light of the renal protection and the cost-effectiveness of this approach, a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria.

The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension

In patients with insufficient blood pressure (BP) control, despite using a combination regimen containing an angiotensin receptor blocker and a calcium channel blocker (CCB), whether a greater dose of CCB or adding a diuretic is more effective at lowering BP remains unclear. We conducted a multicenter randomized clinical trial to compare the efficacy of switching from the daily administration of a single-pill fixed-dose combination of irbesartan (100 mg) and amlodipine (5 mg) to irbesartan (100 mg) with an increased dose of amlodipine (10 mg) (HD group, n=62) or irbesartan (100 mg) and amlodipine (5 mg) with 1 mg of indapamide (D group, n=63) in patients with poorly controlled hypertension. BP measured at home was monitored by a physician using a telemonitoring system. Between the HD and D groups, no significant differences were observed in morning home BP changes (mean reduction of systolic/diastolic BP, 1.7/0.9 mmHg; 95% confidence intervals, −2.4 to 5.7/−1.4 to 3.2; P=0.19/0.37), achievement rate of target BP (45.2% vs. 42.9%, P=0.80), BP variability independent of the mean (P⩾0.74), other variability indices (P⩾0.55) and time to stabilization, which was calculated using a fitted analysis (13.1 days vs. 11.4 days, P=0.99). Although a significant increase in serum uric acid was observed in the D group (P<0.0001), neither clinically relevant abnormal laboratory test results nor critical BP changes were observed throughout the trial period. Both antihypertensive drug combination strategies were effective treatment options. Further investigation is required to determine the appropriate use of both therapies based on the various pathologies associated with hypertension.

Amlodipine suppressed cardiac gene expression of brain natriuretic peptide, transforming growth factor-β1 and fibronectin mediated by aldosterone in male stroke-prone spontaneously hypertensive rats

Objectives  Amlodipine, a calcium channel blocker (CCB), is one of the most common antihypertensive medicines in Japan. We evaluated whether the calcium channel blocker confers cardiac protection through the renin–angiotensin–aldosterone system in male stroke‐prone spontaneously hypertensive rats (SHR‐SP).