The KYOTO HEART Study, which took place in Japan between January 2004 and January 2009, shows that the addition of valsartan to conventional antihypertensive treatment to improve blood pressure control is associated with an improved cardiovascular outcome in Japanese hypertensive patients at high risk of CVD events.

It remains to be determined whether the evidence found in Western countries for the benefit of blockade of the renin-angiotensin system could be directly applied in East Asian populations as a long-term strategy. The KYOTO HEART Study was designed to investigate the add-on effect of valsartan (an angiotensin II receptor antagonist, ARB) versus non-ARB optimal antihypertensive treatment on cardiovascular morbidity and mortality in Japanese hypertensive patients with uncontrolled blood pressure and high cardiovascular risks.

The KYOTO HEART Study was a multicentre, prospective, randomized comparison study with a response-dependent dose titration scheme. More than 3000 Japanese patients were assessed for eligibility (43% female, mean age 66 years); all had uncontrolled hypertension and one or more cardiovascular risk factors (such as diabetes, smoking habit, lipid metabolism abnormality, a history of ischemic heart disease, cerebrovascular disease or peripheral arterial occlusive disease, obesity (BMI>25) and left ventricular hypertrophy on electrocardiogram). 3031 patients were randomized to receive either additional treatment with valsartan or non-ARB conventional therapies.

The primary endpoint was a composite of defined cardio- or cerebrovascular events such as stroke/transient ischemic attack, myocardial infarction, hospitalization for heart failure, hospitalization for angina pectoris, aortic dissection, lower limb arterial obstruction, emergency thrombosis, transition to dialysis, or doubling of serum creatinine levels.

The study was prematurely stopped after a median observation time of 3.27 years. This was for ethical reasons because of unequivocal benefit in the valsartan group.

• Compared with non-ARB arm, fewer individuals in the valsartan arm reached a primary endpoint (83 vs. 155; HR 0.55, 95% CI 0.42-072, p=0.00001). This difference in primary endpoint rate was mainly attributable to reduced incidences of angina pectoris (22 vs. 44; HR 0.51,95% CI 0.31-0.86, p=0.01), stroke/TIA (25 vs. 46; HR 0.55, 95% CI 0.34-0.89, p<0.05).
• Differences in acute myocardial infarction (7 vs. 11), heart failure (12 vs. 26), arteriosclerosis obliterance (11 vs. 12), and aortic dissection (3 vs. 5) were not significant. In addition, rates of all-cause mortality (22 in valsartan arm vs. 32 in non-ARB arm) and cardiovascular mortality (8 vs. 13) were not significant.
• Blood pressure at baseline was 157/88 mmHg in the both groups. Mean blood pressure during the treatment period was 133.1/76.1 mmHg in the valsartan add-on arm and 133.3/76.0 mmHg in the non-ARB arm.

Says principal investigator Professor Hiroaki Matsubara, "The KYOTO HEART Study was first designed to evaluate whether the addition of valsartan to conventional antihypertensive treatment to improve blood pressure control influences the cardiovascular outcome in Japanese high-risk hypertensive patients. The study showed that valsartan has the additional benefits of cardiovascular event prevention for hypertensive patients in East Asia with metabolic syndrome or high-risks."