"Based on the guidelines, these selected Japanese patients were optimally treated from the beginning," lead investigator Dr Björn Dahlöf (Göteborg University, Sweden) told heartwire. "We wanted to test the effects of more aggressive blood-pressure control with valsartan vs just further optimizing the therapy they were on. . . . With the results, we can say that the addition of the angiotensin-receptor blocker was a good choice."

The study, known as the JIKEI HEART study, was presented last week at the World Congress of Cardiology 2006.

In JIKEI HEART, investigators randomized 3081 Japanese patients with hypertension, coronary heart disease, and/or heart failure to conventional therapy or conventional therapy plus valsartan. The aim of the prospective, randomized, open-label, blinded-end-point study was to reduce blood-pressure levels to 130/80 mm Hg, the hypothesis being that the addition of the angiotensin receptor blocker would further improve outcomes. The primary end point was a composite of cardiovascular morbidity and mortality, including stroke or transient ischemic attack, hospitalization for heart failure or angina, dissecting aneurysm of the aorta, lower-limb arterial obstruction, doubling of serum creatinine, or transition to dialysis.

Speaking with heartwire, Dahlöf noted that patients were well matched in both treatment arms. Compared with previous trials in hypertensive patients, blood pressure was well treated from the beginning, with an average baseline blood pressure of 139/81 mm Hg. At randomization, 67% of patients were treated with a calcium-channel blocker, 35% with an ACE inhibitor, and 32% with a beta blocker and 10% were taking diuretics. Approximately one third of patients were treated with statins. In the valsartan-treatment arm, the recommended dose was 40 to 160 mg/day, with 75 mg the average dose prescribed.

Overall, there was no significant difference in blood-pressure reduction or heart rate between the valsartan-treated patients and patients treated without the angiotensin-receptor blocker. The trial, however, was halted early, with a significant cardiovascular benefit observed among those treated with valsartan. In addition to the 39% reduction in the primary end point, significant reductions in stroke, angina, and heart failure were observed. There was no mortality benefit, including cardiovascular mortality, nor was there a reduction in the risk of MI.

Dahlöf said the findings justify the addition of an angiotensin-receptor blocker in Japanese patients, a population with a high prevalence of stroke.

"This was quite a substantial benefit observed over a short period of time," said Dahlöf. "I think the clinical relevance of this trial is that this is the first time the clinical benefit of adding valsartan for blood-pressure control is extended to an Asian population, specifically the Japanese population. This is highly relevant for clinical practice. I think we have to consider even more aggressive blood-pressure control, and not only that, but what kind of agent we use to achieve that control."

Commenting on the results of the study during the hotline session, Dr Xavier Girerd (Broussais Hospital, Paris, France) noted that the reduction in systolic and diastolic blood pressure was much less than that observed in other trials, including the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study, a finding likely attributable to the lower baseline blood-pressure values. As Dahlöf observed, Girerd said that it is still unknown whether or not the benefit of effect is attributable to the maximum blockade of the renin-angiotensin system or through the interaction of valsartan with the calcium-channel blockers or diuretics.

In addition, further analyses are needed to explain the lack of MI benefit despite the 65% reduction in angina pectoris. While the findings are positive and support the use of angiotensin-receptor blockers in the Japanese population, studies are still needed to support the addition of the drugs in European and other populations, said Girerd.