From Medscape Medical News-a professional news service of WebMD

Barcelona, Spain - 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 of NOD in that trial, a 34% reduction in risk relative to those taking atenolol with or without bendroflumethiazide, they report.

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, ASCOT co-principal investigator Dr Peter S Sever (Imperial College, in London, UK) said.

"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," Sever said.

This analysis from ASCOT-BPLA was presented here at the World Congress of Cardiology 2006 by Dr Ajay K Gupta (Imperial College).

New-onset diabetes

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.

ASCOT-BPLA: New onset diabetes by treatment group

	Atenolol-based therapy	Amlodipine-based therapy
n (%)	799 (11.4)	567 (8.0)

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. BMI, HDL-cholesterol, and triglyceride levels were also important baseline predictors.

ASCOT-BPLA: Multivariate Cox proportional hazard model for risk of new-onset diabetes

Factor	Hazard ratio	95% CI	p
Age >55 y (per 5 y)	0.94	0.90-0.96	.006
FPG >5 mmol/L	5.80	5.24-6.43	<0.001
Male sex	0.98	0.84-1.14	0.750
BMI (per 5 units increase)	1.49	1.38-1.62	<0.001
SBP (per 10 mm Hg)	1.07	1.04-1.10	<0.001
Amlodipine+perindopril	0.66	0.59-0.74	<0.001
HDL-C (per mmol/L)	0.72	0.58-0.89	0.002
Triglyceride (per mmol/L)	1.12	1.07-1.17	<0.001
Total cholesterol (per mmol/L)	0.89	0.84-0.94	<0.001
Use of non-CAD medication (Y/N)	1.25	1.11-1.40	<0.001
Alcohol intake (unit/wk)	0.99	0.99-1.00	.017

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.

ASCOT-BPLA: New-onset diabetes by risk quartiles

Quartile	Hazard ratio (95% CI)
First	Referent
Second	2.5 (1.8-3.5)
Third	5.0 (3.7-6.8)
Fourth	19.0 (14.3-25.4)

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+thiazide, the use of amlodipine+perindopril is associated with 34% reduction in the risk for NOD, and this decrease is irrespective of the baseline risk category," Gupta concluded. "The risk model developed is robust, has an excellent discriminative ability, and could potentially play an important role in clinical practice."

Choosing optimal antihypertensive therapy

Invited discussant for this paper was Dr Jose L Zamorano Gomez (Hospital Clinico San Carlos and the Hospital 12 de Octubre de Madrid, Spain). Zamorano said the end point of NOD has been considered in a number of recent antihypertensive trials such as VALUE and ALLHAT, and although NOD was seen to be increased by certain antihypertensive medications, this did not translate into increased clinical events that make up the primary end points of these trials. However, it is likely that longer follow-up will show that the development of new diabetes does actually increase risk, he said.

"Combining the 11 most important risk factors for NOD" reported in this paper by the ASCOT investigators, he said, "it is possible to calculate a risk score that was extremely good at discriminating between risk groups presented in quartiles."

A variety of factors must be considered when an antihypertensive therapy is chosen for individual patients, 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.

The principal sponsor of ASCOT is Pfizer Inc, New York, with support provided by Servier Research Group, Paris, France, and Leo Laboratories, Copenhagen, Denmark. The trial was jointly coordinated by the Imperial College London (International Center for Circulatory Health, National Heart and Lung Institute at St Mary's Hospital, London, United Kingdom) and the Scandinavian Coordinating Center (Scandinavian CRI AB), Göteborg, Sweden.

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