Adding thiazide to a renin–angiotensin blocker improves left ventricular relaxation and improves heart failure in patients with hypertension

Abstract

Hypertension is associated with an increased risk of diastolic dysfunction. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have failed to show improvement in clinical outcomes for patients with diastolic dysfunction. In this study, we investigated the effect of changing an ACEi or ARB to a combination of losartan and hydrochlorothiazide (HCTZ) on left ventricular (LV) preload and relaxation in patients with hypertension and diastolic dysfunction. We enrolled 371 hypertensive patients with diastolic dysfunction who had not achieved their treatment goals with an ACEi or ARB. We switched the ACEi or ARB to losartan/HCTZ and followed the patients for 24 weeks. The primary end points were changes in septal mitral annular velocity during diastole (e′) and in the ratio of mitral inflow velocity to e′ velocity (E/e′ ratio) from baseline to the end of follow-up. Mean systolic and diastolic blood pressures (BP) decreased by 22 and 11 mm Hg, respectively, after changing from an ACEi or ARB to losartan/HCTZ. The e′ velocity increased, and the E/e′ ratio and brain natriuretic peptide level decreased significantly. High-sensitivity C-reactive protein also decreased significantly (0.50 vs. 0.29 mg dl−1, P<0.0001). There were only slight or no changes in glucose levels, homeostasis model assessment insulin resistance (HOMA-R), uric acid and electrolytes after the drug change. Changing from an ACEi or ARB to losartan/HCTZ is associated with a reduction in BP, improvement in LV relaxation, improvement in heart failure state and attenuation of systemic inflammation with few adverse effects in patients with hypertension and diastolic dysfunction.

Release From Glomerular Overload by the Addition of Low-dose Thiazide in Patients With Angiotensin Receptor Blocker-Resistant Hypertension

“…It would be expected that the total body fluid volume would decrease after the addition of thiazide because of the increased elimination of salt. Ito et al reported that switching to losartan/thiazide combination therapy ameliorated chronic heart failure associated with a decrease in BNP and an increase in Cr levels [16]. These results are compatible with those of the current study.…”

Effects of sex and hypertension subtype on haemodynamics and left ventricular diastolic function in older patients with stage 1 hypertension

“…The renin–angiotensin–aldosterone system inhibitors have favourable effects on arterial compliance [39] and left ventricular diastolic function [40], resulting in better clinical outcomes than thiazide monotherapy in patients at lower cardiovascular risks [41]. Moreover, combination therapies of angiotensin receptor blockers and thiazide-type diuretics [39,42], or calcium channel blockers and angiotensin-converting enzyme inhibitors [43] were reported to have more beneficial effects on cardiovascular morbidities [39,42] and outcomes [42,43] in older hypertensive patients. Thus, combined drug treatment might also be recommended for older Stage 1 hypertensive patients, especially women with SDH.…”

Effects of a Fixed Combination of Losartan With Hydrochlorothiazide on Glucose Tolerance in Hypertensive Patients Uncontrolled with Angiotensin II Receptor Blockers Alone

“…The prescription of thiazide, a diuretic, has certain limits, specifically that it does not increase adverse effects [13][14][15] ; however, there are concerns about the glucose tolerance effects of thiazide.…”