title: Efficacy and safety of early versus late titration of fixed-dose irbesartan/hydrochlorothiazide: ACTUAL study.
abstract: Hypertension management guidelines recommend titrating antihypertensive drugs stepwise every 4-6 weeks.We compared efficacy and safety of early versus late titration after 10 weeks' treatment with irbesartan/hydrochlorothiazide. Hypertensive patients uncontrolled on monotherapy were randomized into two groups. In the early titration group (E), patients received irbesartan/hydrochlorothiazide 150/12.5 mg for 2 weeks; uncontrolled patients were up-titrated to 300/25 mg at weeks 2 and 6. In the late titration group (L), patients received 150/12.5 mg for 6 weeks; uncontrolled patients were up-titrated to 300/25 mg at week 6 (W6). The change of mean systolic (SBP) and diastolic blood pressure (DBP) from baseline to week 10 (W10) were studied using a covariance analysis model. The percentage of controlled patients at W10 was compared between groups using Fisher's exact test. Of 833 patients enrolled from 14 countries, the intent-to-treat (ITT) population included 795 (mean age 58 +/- 12 years, female 60%, obesity 38%, diabetes 22%). AtW6, mean SBP decrease was: E - 28.8 mmHg vs L - 26.3 mmHg (p = 0.02). At W10, there was similar mean SBP decrease: E - 29.5 mmHg vs L- 31.0 mmHg (p = 0.14). The control rate at W10 was 58% (E) and 64% (L), p = 0.06. Serious adverse events were more frequent in E (2.5% vs 0.7%, p= 0.044). Both early and late titration regimens provide similar BP decrease and control rate.
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service Endocrinologie, Unité de Prévention Cardiovasculaire, Paris, France. xavier.girerd@psl.aphp.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Girerd
authors.forename: David
authors.initials: D
authors.lastname: Rosenbaum
authors.forename: Joseph
authors.initials: J
authors.lastname: Aoun
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects*; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; C505809:hydrochlorothiazide, losartan drug combination; D006852:Hydrochlorothiazide; D019808:Losartan