Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension

Abstract

Background: Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients.

Objectives: To compare the efficacy of two doses of losartan (LOS)⁄HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg⁄HCTZ 25 mg (LOS100⁄HCTZ25).

Methods: Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100⁄HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg⁄HCTZ 25 mg (group 1; n=53) or LOS 150 mg⁄HCTZ 37.5 mg (LOS150⁄HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions.

Results: At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg⁄HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150⁄HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150⁄HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed.

Conclusions: In patients with uncontrolled systolic ambulatory hypertension receiving LOS100⁄HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150⁄HCTZ37.5 may be an effective strategy that does not affect metabolic parameters.

Figure 1)

Design of the study comparing the effects of losartan (LOS) 150 mg plus hydrochlorothiazide (HCTZ) 25 mg versus LOS 150 mg plus HCTZ 37.5 mg in hypertension patients whose ambulatory systolic blood pressure remained inadequately controlled after six weeks of receiving LOS 50 mg plus HCTZ 12.5 mg followed by six weeks of LOS 100 mg plus HCTZ 25 mg. DASBP Daytime ambulatory systolic blood pressure

Figure 2)

Causes of discontinuation before and after randomization. HCTZ Hydrochlorothiazide; LOS Losartan

Figure 3)

Mean changes from baseline in mean daytime ambulatory systolic (A) and diastolic (B) blood pressure (BP) per study period, with 95% CIs. H25 Hydrochlorothiazide 25 mg; H37.5 Hydrochlorothiazide 37.5 mg; LOS150 Losartan 150 mg

Figure 4)

Additional decreases in mean (± SD) daytime systolic blood pressure (MDSBP) produced by losartan 150 mg/hydrochlorothiazide 25 mg (LOS150/HCTZ25) and losartan 150 mg/hydrochlorothiazide 37.5 mg (LOS150/HCTZ37.5) for elderly (65 years of age or older) and obese (body mass index [BMI] 30 kg/m² or older) patient subgroups