Impact of the combination of an angiotensin II receptor blocker and low-dose hydrochlorothiazide on patients with morning hypertension

Abstract

E pidemiological studies have shown the existence of a circadian pattern in the onset of adverse cardiovascular (CV) events, which occur most frequently in the morning (0600 hours to noon). 1,2 The mechanisms involved in the morning increase in CV events are not well understood. However, Kario et al. 3 have shown an association between the CV events and morning blood pressure (BP) surge. For example, the incidence of stroke in the morning hours was shown to be significantly increased in those with an exaggerated morning BP surge compared with those without. 3 Renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers) are widely recommended as first-line drugs to prevent target organ damage in hypertensive patients at high risk of CV events; however, it is often difficult to achieve the target BP by treatment solely with RAS inhibitors. Recently, the American Society of Hypertension and the European Society of Hypertension recommended the use of a specific combination of agents that elicit different antipressor mechanisms or that block counterregulatory responses, to further reduce BP and to increase the number of patients achieving the BP treatment goal. In addition, in many cases, drug adherence can be enhanced through the use of a combination tablet that contains optimal doses of two or three different agents.Therefore, one of the most intriguing questions in clinical practice for hypertension is determining which combinations and doses of drugs are ideal additions to the first-line RAS inhibitors. BP reduction with a diuretic-based regimen has been shown to decrease the incidence of stroke, heart failure and other CV events. 4 Most of these studies used chlorthalidone, a thiazide-class diuretic; yet, 95% of thiazide prescriptions are for hydrochlorothiazide (HCTZ). 5 Previous studies have documented that the combination of losartan (50 mg) with lowdose HCTZ (12.5 mg) successfully reduced BP in patients with essential hypertension. 6,7 However, there has been no study that tested the hypothesis that selective suppression of an exaggerated morning BP surge leads to a regression of target organ damage and a reduction in subsequent CV events.In this issue of Hypertension Research, Ueda et al. 8 reported an interesting clinical study, in which they compared the efficacy and safety of a losartan (50 mg)/HCTZ (12.5 mg) combination and high-dose losartan (100 mg) in patients with morning hypertension or a morning BP surge. 9 Combination therapy induced a greater reduction in the morning systolic BP than did high-dose losartan therapy (131.5±11.5 vs. 142.5 ± 13.6 mm Hg, Po0.001). As a result, ARB/HCTZ combination therapy had a twofold greater rate of achieving the target morning BP than did high-dose losartan therapy.Recent studies have shown that the addition of low-dose HCTZ (12.5 mg) to losartan (50 mg) once daily significantly decreased the urinary protein/creatinine ratio in hypertensive patients with chronic kidney disease without changing the serum c...