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Hydrochlorothiazide and atenolol combination antihypertensive therapy: effects of drug initiation order.

ABSTRACT: For combination antihypertensive therapy with thiazide diuretics and beta-blockers, the effect of the order of initiation of the drugs on the outcome has not been tested. Patients with uncomplicated hypertension were randomized to receive either hydrochlorothiazide (HCTZ) or atenolol monotherapy, followed by addition of the alternative drug. Blood pressure (BP) responses were evaluated by race and order of drug initiation. A total of 368 participants received combination therapy. Among the participants, blacks showed a greater BP-lowering effect than whites did with HCTZ monotherapy (-13.0/-7.4 mm Hg vs. -8.0/-4.2 mm Hg, P < 0.001) but a smaller BP-lowering effect than did whites with atenolol monotherapy (-1.1/-2.9 mm Hg vs. -9.9/-9.2 mm Hg, P < 0.0001). These differences were not evident during combination therapy. However, both groups showed greater response to HCTZ + atenolol than to atenolol + HCTZ (-19.1/-14.2 mm Hg vs. -15.6/-11.3 mm Hg, P < 0.0001). Despite optimal dosing of HCTZ + atenolol, only two-thirds of the participants achieved BP control. In HCTZ/atenolol combination antihypertensive therapy, the order in which the drugs are initiated affects total BP lowering during the first 4-6 months of therapy.

SUBMITTER: Johnson JA

PROVIDER: S-EPMC2765524 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Hydrochlorothiazide and atenolol combination antihypertensive therapy: effects of drug initiation order.

Johnson J A JA Gong Y Y Bailey K R KR Cooper-DeHoff R M RM Chapman A B AB Turner S T ST Schwartz G L GL Campbell K K Schmidt S S Beitelshees A L AL Boerwinkle E E Gums J G JG

Clinical pharmacology and therapeutics 20090701 5

For combination antihypertensive therapy with thiazide diuretics and beta-blockers, the effect of the order of initiation of the drugs on the outcome has not been tested. Patients with uncomplicated hypertension were randomized to receive either hydrochlorothiazide (HCTZ) or atenolol monotherapy, followed by addition of the alternative drug. Blood pressure (BP) responses were evaluated by race and order of drug initiation. A total of 368 participants received combination therapy. Among the parti ...[more]

PMID: 19571804

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Project description:BackgroundChlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites vs blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients.MethodsWe compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks; 25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional 6 weeks) of PEAR-2 (n = 326) clinical trials, in 17-65-year-old mild-moderate uncomplicated hypertensive whites and blacks.ResultsMean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10-6 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval, 0.07-0.37; P = 3.4e-7).ConclusionCompared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting that the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks.

Project description:This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ?100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were -9.50 (8.46) mmHg in the OM/AML/HCTZ group and -4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).

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Hydrochlorothiazide and atenolol combination antihypertensive therapy: effects of drug initiation order.

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Hydrochlorothiazide and atenolol combination antihypertensive therapy: effects of drug initiation order.

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