The Fixed-Dose Combination of Losartan/Hydrochlorothiazide Elicits Potent Blood Pressure Lowering During Nighttime in Obese Hypertensive Patients

Abstract

BackgroundHypertension is one of the most powerful predictor of the future cardiovascular events, and antihypertensive therapy adopting multiple drug regimen is often needed to obtain the appropriate blood pressure (BP) control. To clarify the blood pressure-lowering effect of the fixed-dose combination (FDC) of an angiotensin receptor blocker (ARB) and diuretic agent in poorly controlled hypertensive patients, we intended a multicenter prospective observational study (Investigation for Normalized Blood pressure control with the Appropriate medication: INBA) by means of the sequential ambulatory blood pressure monitoring (ABPM).MethodsOne hundred and thirteen hypertensive patients who had not achieved the target BP control proposed in the guidelines with medication containing any ARB but without diuretic agents (54 men; mean age, 66 years old; mean office systolic/diastolic BP (SBP/DBP), 158/82 mmHg) were enrolled. Daytime and nighttime blood pressures were assessed with ABPM before and at 12 weeks after switching the ARB to the FDC of 50 mg of losartan, and 12.5 mg of hydrochlorothiazide (HCTZ).ResultsDaytime SBP/DBP (mean ± SD) decreased from 151 ± 14/88 ± 8 mmHg to 140 ± 11/82 ± 8 mmHg (P < 0.001, P < 0.001, respectively), and nocturnal SBP/DBP from 138 ± 18/78 ± 9 mmHg to 125 ± 14/72 ± 9 mmHg (P < 0.001, P < 0.001, respectively) during the 12 weeks treatment. Pulse rate did not change irrespective of the time window. Among various parameters (age, history of hypertension, body mass index (BMI), serum potassium, uric acid, estimated glomerular filtration rate, plasma B-type natriuretic peptide), BMI alone showed significant negative correlation with 12-weeks reduction in nocturnal SBP (r = -0.43, P < 0.05). No parameters correlated with reduction in daytime SBP during this period. Patients with BMI ≥ median (25.8 kg/m2) showed significantly greater reduction in nocturnal SBP for 12 weeks than patients with BMI < median (20.1 ± 15.6 mmHg vs 6.1 ± 10.9 mmHg, P < 0.001) although reduction in daytime SBP was comparable between the two groups (8.9 ± 13.5 mmHg vs 11.9 ± 12.7 mmHg).ConclusionsThe administration of the FDC of losartan/HCTZ lowers BP both in day- and nighttime, and the nocturnal antihypertensive potency is remarkable in obese patients.

Antihypertensive effectiveness of combination therapy with losartan/hydrochlorothiazide for ‘real world’ management of isolated systolic hypertension

“…This study confirmed these data in relatively large numbers of patients. 5.6 ± 1.4 5.9 ± 1.4 5.9 ± 1.5 5.8 ± 1.4 5.8 ± 1.4 Serum creatinine (mg/dl) 0.84 ± 0.44 0.91 ± 0.54 0.92 ± 0.62 0.91 ± 0.5 0.89 ± 0.46 Serum potassium (mEq/l) 4.2 ± 0.9 4.3 ± 0.8 4.2 ± 0.5 4.1 ± 0.3 4.4 ±0.5 In addition, total cholesterol levels were not changed during the study period, a finding already reported by several investigators [Hirose et al 2011;Racine et al 2010;Ibuki et al 2014].…”

Lercanidipine/enalapril combination in the management of obesity-related hypertension

“…Almost superimposable results were obtained in a smaller study, in which, however, the use of 24-hour ambulatory blood pressure monitoring allowed the confirmation of efficacy of the combination losartan/hydrochlorothiazide throughout the 24-hour period, and particularly during the nighttime in obese hypertensive patients aged more than 65 years. 11 Similar effects were obtained in other studies in which the combination was based on angiotensin II receptor blockers and diuretics or β-blockers and diuretics. 12 – 15 Finally, results of two recent meta-analyses, one based on the data collected in three clinical trials recruiting more than 12,000 patients and the other in seven controlled clinical trials recruiting about 6,000 hypertensive patients, have provided evidence that the combination valsartan/amlodipine or aliskiren/amlodipine may guarantee a blood pressure control of similar magnitude both in nonobese and in obese patients.…”

“… 21 , 22 The effects of anti-hypertensive drug combination treatment on these different targets have been investigated in few studies specifically performed in obese hypertensive patients; however, as mentioned, the combination losartan/hydrochlorothiazide has been shown to restore the blood pressure reduction occurring during nighttime. 11 Similar effects have been reported for the telmisartan/hydrochlorothiazide as well as for the fosinopril/hydrochlorothiazide combination, 23 , 24 while pulse pressure values have been shown to be significantly reduced by valsartan/hydrochlorothiazide. 13 , 25 In general terms, the results of these studies suggest that the drug combination more effective in correcting the abnormalities of the blood pressure profile described in the obese hypertensives should necessarily include a drug acting on the renin–angiotensin system.…”