title: Combination angiotensin-receptor blocker (ARB)/calcium channel blocker with HCTZ vs the maximal recommended dose of an ARB with HCTZ in patients with stage 2 hypertension: the exforge as compared to losartan treatment in stage 2 systolic hypertension (EXALT) study.
abstract: This study compared the efficacy and safety of combination angiotensin-receptor blocker (ARB)/calcium-channel blocker (CCB) with hydrochlorothiazide (valsartan/amlodipine/HCTZ 160/5/2mg) vs maximal available combination doses of an ARB with HCTZ (losartan/HCTZ 100/25 mg) in the management of stage 2 hypertension. After 1 to 2 weeks of antihypertensive drug washout, patients with a mean sitting systolic blood pressure (MSSBP) of ≥ 160 mm Hg and <200 mm Hg were randomized to valsartan/amlodipine 160/5 mg (n = 241) or losartan 100 mg (n = 247). At week 3, HCTZ 25 mg was added to both treatments. The primary end point, reduction in MSSBP from baseline to week 6, was significantly greater in the valsartan/amlodipine group than in the losartan group (least-squares [LS] mean change, -31.8 mm Hg vs -26.4 mm Hg; P<.001). Additional reductions occurred after titrating to 320/10/25 mg at week 6 in the valsartan/amlodipine group and switching from losartan/HCTZ to valsartan/amlodipine/HCTZ (week 6, 160/5/25 mg; week 9, 320/10/25 mg) in the losartan group. Achievement of blood pressure <140/90 mm Hg also favored the valsartan/amlodipine group. Dizziness was the only adverse event reported in >5% of patients (5.4% valsartan/amlodipine group, 3.6% losartan group). Moderate doses of an ARB/CCB combination with HCTZ reduced blood pressure more effectively than the maximal dose of an ARB with HCTZ.
authors.affiliation: Pacific Heart Institute, Santa Monica, CA 90404, USA. rwright@pacificheart.com
authors.forename: Richard F
authors.initials: RF
authors.lastname: Wright
authors.forename: Daniel
authors.initials: D
authors.lastname: Duprez
authors.forename: Das
authors.initials: D
authors.lastname: Purkayastha
authors.forename: Rita
authors.initials: R
authors.lastname: Samuel
authors.forename: Keith C
authors.initials: KC
authors.lastname: Ferdinand
mesh_terms: D017311:Amlodipine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine; D019808:Losartan