Novartis announced the results of VALUE (Valsartan Antihypertensive Long-term Use Evaluation Trial) a prospective, double-blind, randomised, active-controlled study, a company release said.

The VALUE trial complements the long-term cardioprotective profile of Diovan and suggests potential new benefits in lowering the incidence of new onset diabetes with Diovan in hypertensive patients at high cardiovascular risk. The study highlights the need for both aggressive blood pressure lowering as well as cardiac and metabolic protective regimens in this patient population.

VALUE was a study of a Diovan (valsartan)-based regimen vs. an amlodipine-based regimen in 15,245 high blood pressure patients at risk for cardiovascular complications because of co-existing diseases or risk factors such as diabetes, history of stroke, and coronary artery disease. The trial was designed to test, for the same level of blood pressure control, whether a Diovan-based treatment regimen would be more effective than an amlodipine-based treatment regimen in reducing cardiac mortality and morbidity in these high-risk patients.

There was no difference with respect to the incidence of the primary endpoint of cardiac mortality and morbidity between the two treatment groups (10.6% [n=810] for the Diovan regimen vs. 10.4% [n=789] for the amlodipine regimen; p=0.49), no statistically significant difference between the Diovan and amlodipine treatment groups in death from heart attack (0.86% [n=66] vs. 0.84% [n=64] respectively; p=0.81) and no statistically significant difference between the Diovan and amlodipine treatment groups in all-cause death (11.0% [n=841] vs. 10.8%, [n=818]; p=0.45). The two treatment regimens effectively lowered blood pressure.

Despite unintended blood pressure differences especially early in the trial in favour of amlodipine-based regimen, there was no statistically significant difference in the primary composite cardiac morbidity and mortality endpoint. However, these unintended differences make interpretation of the secondary endpoints difficult.

The Diovan-based regimen was associated with a reduction in new onset of diabetes by 23% vs. the amlodipine-based regimen (13.1% [n=690] vs. 16.4% [n=845]; p<0.001).

Patients in VALUE were men and women aged 50 or older with high blood pressure and additional cardiovascular risk factors or cardiovascular disease. The mean age of patients was 67.2 years. Co-existing risk factors and diseases for patients at the start of the study included coronary heart disease (45.8% of patients), type 2 diabetes (31.7%), and history of stroke or transient ischaemic attack (19.8%).

"Since hypertension regimens studied in previous trials may increase the risk of diabetes and as amlodipine is known to be neutral on glucose metabolism, this finding in VALUE is especially significant at a time when the prevalence of the condition continues to increase throughout the developed world," said Stevo Julius, VALUE lead investigator and professor, Internal Medicine and Physiology, Frederick G.L. Huetwell, professor of Hypertension, University of Michigan, Ann Arbor.

While the VALUE trial demonstrated better blood pressure control compared to certain other large-scale studies, 40 per cent of patients in this high-risk population did not achieve the predefined blood pressure goal (less than 140/90 mm Hg). This highlights the need for earlier and more aggressive dose titrations as well as add-on therapies with proven combination regimens that can get high risk cardiovascular patients to goal and protect them from adverse cardiovascular outcomes.

Patients in the Diovan-based group were half as likely (15% vs. 33%) to experience the most frequently reported side effect, peripheral oedema. Adverse events reported more frequently in the Diovan-based group vs. the amlodipine-based group respectively included dizziness and headache.

According to the release, the Diovan clinical trial programme is one of the world's largest in cardiovascular research, involving approximately 50,000 patients including more than 9,500 patients with diabetes. Besides VALUE, recently completed Diovan trials include VALIANT in post-heart attack patients and Val-HeFT in heart failure patients.

The study, presented at the European Society of Hypertension meeting and simultaneously published online in The Lancet, was conducted at 934 clinical sites in 31 countries.