Valsartan Vs. Amlodipine in Prevention of Type 2 Diabetes

Valsartan is significantly superior to amlodipine for prevention of new-onset type-2 diabetes in high-risk patients with hypertension.Tesaglitazar Shows Promise in This protective effect for valsartan is most pronounced in patients with the highest risk scores, said the researchers.
Sverre E. Kjeldsen, MD, PhD, Associate Chairman of the VALUE trial, Chief Physician and Professor in Cardiology, Department of Cardiology, Ullevaal Hospital, University of Oslo, Norway, and Adjunct Professor, Department of Cardiovascular Medicine, University of Michigan, Michigan, United States, presented the results of the international, multicenter, randomized, double-blind study on behalf of the VALUE trial Investigators.

The present analysis arose from indications during the VALUE trial that older therapies (beta blockers and diuretics) development of diabetes mellitus compared to newer therapies (calcium channel blockers, angiotensin II receptor blocker and angiotensin converting enzyme inhibitors).

The VALUE trial enrolled 15,313 men and women with treated or untreated hypertension, aged 50 years or older; and with one or more defined cardiovascular risk factors or disease.

For their analysis of new-onset diabetes, Dr. Kjeldsen and colleagues exclude the 5250 patients with diabetes at baseline. The baseline characteristics of the remaining nondiabetic patients remained well matched between the 5032 subjects in the valsartan group and 4963 in the amlodipine group.

Their qualifying risk factors were also well matched: high cholesterol, 35.3%/35.9%; current smoking, 25.7%/26.3%; proteinuria, 19.7%/19.5%; LVH without strain, 13.0%/12.6%; elevated serum creatinine, 3.8%/3.3%. Similarly, the associated diseases were: coronary heart disease, 48.9%/48.8%; peripheral artery disease, 14.7%/14.8%; stroke or transient ischemic attack, 22.0%/21.4%; and LVH with strain, 6.3%/6.6%.

This analysis included three pre-specified protocols for detection of new-onset diabetes within the VALUE population without diabetes at randomization: adverse events database (AED); concomitant medication database (CMD); final fasting glucose 7.0 mmoles/L or greater (IFFG). Patients could qualify through any single or combinatorial criteria, but were only counted once.

Subjects were randomized to treatment with the once-daily angiotensin II receptor blocker valsartan 80/160 mg or the calcium channel blocker amlodipine 5/10 mg for 72 months. After 2 months, the diuretic hydrochlorothiazide 12.5/25 mg once daily or other add-on medication could be used at the discretion of the investigators.

There was no significant difference between regimens for the primary composite cardiac endpoint of the full VALUE trial, (valsartan vs. amlodipine hazard ratio (HR), 1.03; P =.49).

With an average follow-up of 4.2 years, there was significantly more new-onset diabetes in the amlodipine arm (14.5% vs. 11.5%; P <.0001). When analysed according to the individual criteria, this significant increase with amlodipine remained (AED, 6.5%/8.8%, P < .0001; CMD, 5.0%/6.0%, P = .0365); IFFG, 6.2%/7.8%, P = .002).

Univariate analysis identified 28 potential predictors of new-onset diabetes, with 14 of them highly significant (P < .001). At the multivariate level, six of these variables remained — glucose level, body mass index, prior beta-blocker/diuretic treatment, white race, age, and heart rate.

With the two study arms providing very similar risk models, their combination was divided into tertiles according to this risk modeling. In the higher risk tertiles, the percentages of patients who developed new-onset diabetes were highly influenced by these factors, with the odds ratios (OR) for valsartan versus amlodipine of: 1st tertile (low risk; n = 3331), 4.1%, OR 0.91 (P = .5704); 2nd tertile (medium risk; n = 3332), 8.5%, OR 0.71 (P = .0058); 3rd tertile (high risk; n = 3332), 26.4%, OR 0.77 (P = .0007).

In summarizing, Dr Kjeldsen indicated that this more pronounced benefits of valsartan over amlodipine in patients with the greatest susceptibility for developing diabetes may well arise from a beneficial effect of valsartan on glucose metabolism.

[Study title: Effects of Valsartan Compared to Amlodipine on Preventing Type 2 Diabetes in High-Risk Hypertensive Patients. The VALUE trial. Abstract 3B1] Presented June 18th at the 15th European Meeting on Hypertension (EMH).

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