Efficacy and Tolerability of Amlodipine Camsylate/Losartan 5/100-mg Versus Losartan/Hydrochlorothiazide 100/12.5-mg Fixed-Dose Combination in Hypertensive Patients Nonresponsive to Losartan 100-mg Monotherapy

• Published in: Clinical therapeutics Vol. 36; no. 10; pp. 1402 - 1411
• Main Authors: Suh, Soon Yong, MD, PhD, Ahn, Taehoon, MD, PhD, Bae, Jang-Ho, MD, PhD, Lim, Do-Sun, MD, PhD, Lee, Seoung Uk, MD, PhD, Kim, Young Kwon, MD, PhD, Hyon, Min Su, MD, PhD, Kim, Won Ho, MD, PhD, Han, Kyoo Rok, MD, PhD, Park, Hoon Ki, MD
• Format: Journal Article
• Language: English
• Published: Bridgewater, NJ Elsevier Inc 01-10-2014; Elsevier; Elsevier Limited
• Subjects: Adult; amlodipine; Amlodipine - administration & dosage; Amlodipine - adverse effects; Amlodipine - therapeutic use; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Cholesterol; Double-Blind Method; Drug Combinations; Drug dosages; Drug therapy; Female; Heart attacks; Humans; Hydrochlorothiazide - administration & dosage; Hydrochlorothiazide - adverse effects; Hydrochlorothiazide - therapeutic use; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Internal Medicine; Laboratories; losartan; Losartan - administration & dosage; Losartan - adverse effects; Losartan - therapeutic use; Male; Medical Education; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Population; Treatment Outcome; losartan; hypertension; amlodipine; Antianginal agent; Imidazole derivatives; Benzothiadiazine derivatives; Tetrazole derivatives; Toxicity; Calcium antagonist; Peptide hormone; Non peptide compound; Cardiovascular disease; Diuretic; Octapeptide; Losartan; Dihydropyridine derivatives; Angiotensin II; Human; Hypertension; Treatment efficiency; Hydrochlorothiazide; Renin angiotensin system; Biphenyl derivatives; Sulfonamides; Amlodipine; Antihypertensive agent; Sartan derivatives; Angiotensin antagonist; Thiazide; Monotherapy; Comparative study
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2014.07.003

Abstract Purpose The aim of this study was to determine whether the efficacy and tolerability of amlodipine camsylate/losartan 5/100 mg/d (AML/LOS) are noninferior to those of losartan/hydrochlorothiazide 100/12.5 mg/d (LOS/HCTZ) fixed-dose combination in hypertensive patients unresponsive to losartan 100-mg/d monotherapy. Methods Male and female patients aged ≥18 years with hypertension despite 4-week, stable treatment with losartan 100-mg/d monotherapy were eligible for inclusion in this multicenter, randomized, double-blind study. Patients were randomly assigned to receive AML/LOS or LOS/HCTZ once daily for 8 weeks. The primary end point was the change from baseline to week 8 in sitting diastolic blood pressure (ΔsiDBP), and the secondary end points were the changes from baseline to 4 weeks in siDBP and sitting systolic BP (ΔsiSBP) and changes from baseline to 4 and 8 weeks in BP response rate. Tolerability was evaluated by physical examination, including vital sign measurement; laboratory analysis; and ECG. Findings Of 275 patients screened at 9 cardiovascular centers, 199 were enrolled (AML/LOS, n = 101; LOS/HCTZ, n = 98), and 183 completed the study. The demographic characteristics were similar between the 2 groups (mean age, 51.56 [9.97] years; men, 70.53%). At 8 weeks, the mean ΔsiDBP values were –11.54 (7.89) and –9.05 (6.57) mm Hg in the AML/LOS and LOS/HCTZ groups, respectively (both, P < 0.0001 vs baseline). The mean difference between the 2 groups was –2.57 mm Hg, a nonsignificant difference, meaning that AML/LOS was noninferior to LOS/HCTZ with regard to the primary end point. At 8 weeks, the mean uric acid level was changed significantly from baseline in the LOS/HCTZ group (+0.41 [0.80] mg/dL; P < 0.0001) but not in the AML/LOS group (–0.12 [0.82] mg/dL), representing a significant intergroup difference ( P < 0.0001). Nineteen patients each in the AML/LOS (18.81%) and LOS/HCTZ (20.00%) groups experienced ≥1 adverse event, with 4 (3.96%) and 3 (3.16%) patients, respectively, experiencing 1 or more events considered by the investigators to have been treatment related. Implications The efficacy and tolerability of AML/LOS 5/100 mg/d was found to have been noninferior to those of LOS/HCTZ 100/12.5 mg/d in these hypertensive patients nonresponsive to losartan 100-mg/d monotherapy.