Hypertension Increase Risk Factors For New-Onset Diabetes

Further analysis of patients who developed diabetes during the Anglo-Scandinavian Cardiac Outcomes Trial – Blood Pressure Lowering Arm (ASCOT-BPLA) has allowed investigators to create a risk score that appears to discriminate those at highest risk for development of new-onset diabetes (NOD) during antihypertensive therapy. Assignment to amlodipine with or without perindopril therapy was associated with a lower risk for NOD in that trial, a 34% reduction in risk relative to those taking atenolol with or without bendroflumethiazide, they report.

Peter S. Sever, PhD, from the Imperial College, in London, United Kingdom, stated that, other factors associated with new diabetes risk that were perhaps "not a surprise" were elevated baseline fasting plasma glucose and triglycerides and decreased HDL cholesterol..

"Overall, almost 10% of patients in the trial developed diabetes, so if you’re hypertensive, you really are at increased risk of getting diabetes, and if you’re on a beta blocker, it’s even worse," Prof. Sever said.

The ASCOT trial was designed to provide further data on outcomes with newer agents over standard therapy with beta blockers and diuretics and begin to provide some information on combinations of agents. The trial enrolled 19,257 hypertensive patients with at least 3 other cardiovascular risk factors from 650 general practices in the United Kingdom, Ireland, Sweden, Finland, Denmark, Norway, and Iceland.

Patients were randomized to 1 of 2 antihypertensive regimens: amlodipine (5/10 mg) (Norvasc, Pfizer), with perindopril (4/8 mg) (ACEON, CV Therapeutics/Solvay Pharmaceuticals; Coversyl, Servier) added as required; or atenolol (50/100 mg) (Tenormin, AstraZeneca), with or without the thiazide diuretic bendroflumethiazide (1.25 – 2.5 mg). Further treatment with other agents could be added as required to reach a target blood pressure (BP) of 140/90 mm Hg or less.

A reduction in all-cause mortality seen with the amlodipine/perindopril strategy caused the trial to be stopped in November 2004. A 10% reduction in nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), the primary end point of the trial, did not reach statistical significance, a finding that the researchers attribute to the early stop of the trial.

Recent British recommendations for the treatment of hypertension no longer include beta blockers as first-line or even second- or third-line drugs for patients with uncomplicated hypertension, although they are still recommended for patients who also have CHD.

A variety of secondary analyses of the ASCOT data have subsequently been published or reported. In the present analysis, investigators determined risk predictors for NOD, which had been a prespecified end point in the trial, and hoped to develop a risk score that might help to identify those at higher risk.

In the amlodipine/perindopril treatment group, 7074 patients were not diabetic at the start of the trial, similar to 7046 in the atenolol/diuretic group. As previously reported, more patients on atenolol-based therapy developed NOD than in the amlodipine-based therapy arm.

Fasting plasma glucose (FPG) was the most robust risk factor and antihypertensive therapy with amlodipine with perindopril was the strongest protective factor among baseline predictors of NOD. Body-mass index (BMI), HDL-cholesterol (HDL-C), and triglyceride levels were also important baseline predictors.

They then divided the population into quartiles for risk based on these factors and showed that in the highest quartile, the risk for NOD was almost 20 times higher than in the lowest quartile.

In each quartile, those in the group taking atenolol with or without thiazide had a higher risk for NOD than those taking amlodipine with or without perindopril, the authors noted.

"Compared with use of atenolol with or without thiazide, the use of amlodipine with or without perindopril is associated with a 34% reduction in the risk for NOD, and this decrease is irrespective of the baseline risk category," Dr. Gupta concluded. "The risk model developed is robust, has an excellent discriminative ability, and could potentially play an important role in clinical practice."

A variety of factors must be considered when an antihypertensive therapy is chosen for individual patients, Dr. Zamorano concluded; whether the patient has heart failure, is post-MI, or has diabetes or renal failure. "We need to add new-onset diabetes to factors considered when selecting the optimal treatment for patients," he said.

This analysis from ASCOT-BPLA was presented in Barcelona, Spain at the World Congress of Cardiology 2006 by Ajay K. Gupta, MD, also from the Imperial College in London.

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FACT:
New Hypertension Pills Cut Diabetes Risk by A Third: Researchers have reported that patients given a specific combination of new blood pressure drugs are one-third less likely to develop diabetes than those on older pills. Read and print the full news article at: https://www.diabetesincontrol.com/modules.php?name=News&file=article&sid=4129