title: Efficacy and safety of combination therapy using high- or low-dose hydrochlorothiazide with valsartan or other Angiotensin-receptor blockers.
abstract: Only a minority of patients treated for hypertension achieve controlled blood pressure (BP) levels. Therapy with fixed-dose combinations of an angiotensinreceptor blocker (ARB) and low-dose hydrochlorothiazide (HCTZ) is commonly prescribed but not always sufficient to achieve the target BP. The efficacy and safety of the fixed-dose combination of valsartan 160 mg and HCTZ 25 mg was evaluated in patients in whom BP had not been controlled with a fixed-dose combination of another ARB and low-dose HCTZ (12.5 mg) in a multicenter trial. After a wash-out period for antihypertensive drugs, patients with a mean sitting diastolic BP (DBP) at trough (3)100 mm Hg but <110 mm Hg were treated with candesartan cilexetil 16 mg plus HCTZ 12.5 mg or telmisartan 80 mg plus HCTZ 12.5 mg for 4 weeks (phase 1). Patients whose BP was still uncontrolled (DBP (3)90 mm Hg) after 4 weeks of therapy were then given valsartan 160 mg plus HCTZ 25 mg for an additional 4 weeks (phase 2). The primary efficacy parameter was the reduction in DBP between week 4 and week 8 in the intention-to-treat (ITT) population. BP reduction during phase 1 was -14.3+/-11.3/-7.5+/-3.9 mm Hg. DBP was controlled in 26% of the patients after phase 1. In patients treated with valsartan 160 mg plus HCTZ 25 mg during phase 2, DBP decreased by an additional 10.3+/-6.5 mm Hg and the mean sitting systolic BP (SBP) by an additional 11.0+/-11.7 mm Hg. The additional decrease was significant (P<.0001) for both parameters and independent of the fixed-dose combination used during phase 1. Among patients whose BP remained uncontrolled during phase 1, 74% achieved a controlled DBP after phase 2. The incidence of adverse events during both phases was comparably low and the results of laboratory tests were unremarkable. Treatment with valsartan 160 mg/HCTZ 25 mg offered a substantial benefit for patients with hypertension not controlled with the combination of candesartan cilexetil 16 mg or telmisartan 80 mg and low dose HCTZ, while maintaining a comparable safety and tolerability profile.
authors.affiliation: Sophien- und Hufeland-Klinikum, Weimar, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Fuenfstueck
authors.forename: R-D
authors.initials: RD
authors.lastname: Hempel
authors.forename: A
authors.initials: A
authors.lastname: Ansari
authors.forename: G
authors.initials: G
authors.lastname: Weidinger
authors.forename: S
authors.initials: S
authors.lastname: Klebs
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology; D001713:Biphenyl Compounds; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000077333:Telmisartan; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068756:Valsartan; D014633:Valine; C081643:candesartan; D000077333:Telmisartan