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

Abstract

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.

Analysis of antihypertensive treatment using real-world Japanese data—the retrospective study of antihypertensives for lowering blood pressure (REAL) study

“…The prescription led to achievement of a lower blood pressure goal (<120 mm Hg systolic blood pressure), which in turn resulted in lower rates of major cardiovascular events and death. A randomized controlled trial showed that adding diuretics to a single pill fixed-dose combination of an ARB and CCB was effective, similar to an increase in the CCB dose [17]. A subanalysis of a clinical trial performed in Japan suggested that the combination of an ARB with a diuretic might provide better cardiovascular outcomes than combination with a βblocker, even in patients with poor blood pressure control [18].…”

Treatment patterns and adherence to antihypertensive combination therapies in Japan using a claims database

“…Diuretics, for example, can cause urinary frequency, erectile dysfunction, fatigue, and muscle cramps, which may be intolerable to patients [25]. Diuretics can also induce metabolic and electrolyte abnormalities, which may lead to their discontinuation by physicians [26].…”

Dihydropyridines as Calcium Channel Blockers: An Overview

“…Nifedipine may possibly meet the requirements of being a selective antagonist by exerting its best effect on the vessels compared to the myocardium, and also has no (or very little) effect on nodal tissue or atrioventricular conduction; The problem is that its selectivity for vessels is associated with rapid uptake and plasma distribution, as well as a rapid rate of fixation to its "receptor" in the complex of the calcium ion channel, for this reason produces rapid peripheral vasodilation. As a consequence, the autonomic nervous system is stimulated, determining a rapid and significant increase of the heart rate, which forces to concomitant treatment with β-blocker or a preparation of prolonged release [24][25][26][27][28][29].…”