title: Efficacy and tolerability of a combination tablet of candesartan cilexetil and hydrochlorothiazide in insufficiently controlled primary hypertension--comparison with a combination of losartan and hydrochlorothiazide.
abstract: This randomized, double-blind study compared the antihypertensive effect, safety and tolerability of a candesartan cilexetil/hydrochlorothiazide (candesartan/HCT; 16/12.5 mg) combination tablet with that of a losartan/HCT (50/12.5 mg) combination tablet in patients with mild-to-moderate primary hypertension insufficiently controlled on previous monotherapy. Men and women, aged 20-80 years, with a sitting diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg and sitting systolic blood pressure (SBP) < or = 200 mmHg during treatment with any kind of antihypertensive monotherapy for at least 4 weeks were randomized to candesartan/HCT or losartan/HCT once daily for 12 weeks. All BP measurements were performed 24 h after previous dose. Mean values and standard deviations (SD) or confidence intervals (CI) are given. A total of 340 patients were enrolled, of whom 299 (144 women and 155 men, mean age 59.5 [10.5] years) were randomized to candesartan/HCT (n = 151) or losartan/HCT (n = 148). BPs at randomization were 159.5 (15.4)/98.4 (5.8)mmHg and 160.5 (16.1)/98.5 (5.4)mmHg, respectively. There was a greater reduction in BP with candesartan/HCT than with losartan/HCT: DBP -10.4 (-11.8; -8.9) vs -7.8 (-9.3; -6.3) mmHg, difference between treatments -2.6 (-4.7; -0.5) mmHg (p = 0.016); SBP -19.4 (-22.1; -16.7) vs - 13.7 (-16.5; - 10.9) mmHg, difference between treatments -5.7 (-9.6; -1.8) mmHg (p = 0.004). The proportion of patients achieving a DBP < or = 90 mmHg was greater in the candesartan/HCT group: 60.9 (53.1; 68.7) vs 49.3 (41.3; 57.4)% (p = 0.044). There were 12 withdrawals in the candesartan/HCT group, of which 8 were due to adverse events, and 17 and 12, respectively in the losartan/HCT group. We conclude that the combination of candesartan and HCT reduces BP effectively and is well tolerated. BP was normalized in 61% of these patients who had insufficient response to previous monotherapy. The reduction in BP and the proportion of patients with normalized BP were greater with the candesartan/HCT 16/12.5 mg combination than with the losartan/ HCT 50/12.5 mg combination.
authors.affiliation: Department of Medicine and Care, Faculty of Health Sciences, University Hospital, Linköping, Sweden. peter.ohman@astrazeneca.com
authors.forename: K P
authors.initials: KP
authors.lastname: Ohma
authors.forename: H
authors.initials: H
authors.lastname: Milon
authors.forename: K
authors.initials: K
authors.lastname: Valnes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C077793:candesartan cilexetil