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Predictors for glucose change in hypertensive participants following short-term treatment with atenolol or hydrochlorothiazide.

ABSTRACT: To develop and validate a predictive model for glucose change and risk for new-onset impaired fasting glucose in hypertensive participants following treatment with atenolol or hydrochlorothiazide (HCTZ).Randomized multicenter clinical trial.A total of 735 white or African-American men and women with uncomplicated hypertension.Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) is a randomized clinical trial to assess the genetic and nongenetic predictors of blood pressure response and adverse metabolic effects following treatment with atenolol or HCTZ. To develop and validate predictive models for glucose change, PEAR participants were randomly divided into a derivation cohort of 367 and a validation cohort of 368. Linear and logistic regression modeling were used to build models of drug-associated glucose change and impaired fasting glucose (IFG), respectively, in the derivation cohorts. These models were then evaluated in the validation cohorts. For glucose change after atenolol or HCTZ treatment, baseline glucose was a significant (p<0.0001) predictor, explaining 13% of the variability in glucose change after atenolol and 12% of the variability in glucose change after HCTZ. Baseline glucose was also the strongest and most consistent predictor (p<0.0001) for development of IFG after atenolol or HCTZ monotherapy. The area under the receiver operating curve was 0.77 for IFG after atenolol and 0.71 after HCTZ treatment, respectively.Baseline glucose is the primary predictor of atenolol or HCTZ-associated glucose increase and development of IFG after treatment with either drug.

SUBMITTER: Moore MJ

PROVIDER: S-EPMC4227953 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Predictors for glucose change in hypertensive participants following short-term treatment with atenolol or hydrochlorothiazide.

Moore Mariellen J MJ Gong Yan Y Hou Wei W Hall Karen K Schmidt Siegfried O F SO Curry Robert Whitney RW Beitelshees Amber L AL Chapman Arlene A Turner Stephen T ST Schwartz Gary L GL Bailey Kent K Boerwinkle Eric E Gums John G JG Cooper-DeHoff Rhonda M RM Johnson Julie A JA

Pharmacotherapy 20140909 11

<h4>Study objective</h4>To develop and validate a predictive model for glucose change and risk for new-onset impaired fasting glucose in hypertensive participants following treatment with atenolol or hydrochlorothiazide (HCTZ).<h4>Design</h4>Randomized multicenter clinical trial.<h4>Patients</h4>A total of 735 white or African-American men and women with uncomplicated hypertension.<h4>Measurements and main results</h4>Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) is a randomize ...[more]

PMID: 25202885

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Project description:IntroductionIn most treated patients with hypertension, a two or more drug combination is required to achieve adequate blood pressure (BP) control. In our study we assessed whether the combination of zofenopril + hydrochlorothiazide (HCTZ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor, uncontrolled by a previous monotherapy.MethodsAfter a 2-week placebo washout, 361 treated hypertensive patients [office sitting diastolic BP (DBP), ≥90 mmHg], aged 18-75 years, were randomized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily, in an international, multicenter study. After the first 6 and 12 weeks, zofenopril and irbesartan doses could be doubled in non-normalized subjects. The primary study end point was the office sitting DBP reduction after 18 weeks of treatment. Secondary end points included office systolic BP (SBP), ambulatory BP and high sensitivity C-reactive protein (hs-CRP).ResultsThe between-treatment difference for office DBP averaged to +1.0 (95% CI -0.4, +0.8) mmHg (P = 0.150), the upper limit of the 95% confidence interval being inferior to the protocol-defined non-inferiority limit (3 mmHg). In the subset of patients with valid ambulatory BP, no difference in 24-h average DBP [n = 181; 6.7 (8.7, 4.6) zofenopril + HCTZ vs. 6.3 (8.8, 3.7) mmHg irbesartan + HCTZ, P = 0.810] and SBP reductions [11.7 (15.4, 8.0) vs. 12.6 (17.2, 8.0) mmHg, P = 0.758] were observed between the two treatment groups. hs-CRP was reduced by zofenopril + HCTZ [-0.52 (-1.05, 0.01) mg/L], while it was increased by irbesartan plus HCTZ [0.97 (0.29, 1.65) mg/L, P = 0.001 between treatments].ConclusionIn previously monotherapy-treated, uncontrolled patients with hypertension, zofenopril 30-60 mg + HCTZ 12.5 mg is as effective as irbesartan 150-300 mg plus HCTZ 12.5 mg, with the added value of a potential protective effect against vascular inflammation.

Dataset Information

Predictors for glucose change in hypertensive participants following short-term treatment with atenolol or hydrochlorothiazide.

Publications

Predictors for glucose change in hypertensive participants following short-term treatment with atenolol or hydrochlorothiazide.

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