Data from the independent KYOTO HEART study, presented recently at the European Society of Cardiology Congress in Barcelona, Spain, and published online in the European Heart Journal demonstrated that the addition of the angiotensin receptor blocker (ARB) Diovan (valsartan) to a non-ARB-based treatment regimen for high blood pressure provided a significant 45% relative risk reduction in cardiovascular events including stroke, compared to conventional non-ARB treatment regimen.
A total of 3,031 Japanese patients with uncontrolled high blood pressure either with no treatment or on a previous non-ARB-based regimen and with one or more pre-defined cardiovascular risk factors (e.g. existing diabetes, obesity, smokers, or a history of cardiovascular disease) took part in the study.
“These findings are useful to Canadian physicians who are working with their patients to prevent long-term complications of high blood pressure, such as stroke” said Peter Lin, Toronto, Ontario. “This study followed high risk patients commonly seen in clinical practice and while the results reinforce that getting blood pressure down is important, choosing the right treatment to get there is vital because some medicines have additional protective benefits.”
“The KYOTO HEART study confirms that valsartan can significantly reduce the incidence of the composite of heart, brain and vascular complications in patients at high risk of cardiovascular events, independent of its blood pressure-lowering efficacy,” said Hiroaki Matsubara, professor of cardiovascular medicine at the Kyoto Prefectural University of Medicine, Kyoto, Japan and principal investigator of the KYOTO HEART study. “In addition, the study also confirms that the numerous benefits of blockade of the renin angiotensin system extend to East Asian patients.”
While the cardiovascular risk profile of Japanese patients has historically been different to that of Caucasians and African-Americans, general changes in lifestyle throughout East Asia in recent years have resulted in the Japanese risk profile becoming more similar to that of western populations.
“KYOTO HEART enrolled patients with high rates of metabolic syndrome and obesity, and numerous smokers,” said professor Gordon T McInnes, Clinical Pharmacology, University Division of Cardiovascular and Medical Sciences, Western Infirmary, Glasgow, UK. “For this reason, the results of this study may not only be relevant to patients with high blood pressure in Japan, but also other populations where such risk factors are highly prevalent.”
More details on the study
The study participants were randomised to receive either Diovan add-on therapy or a non-ARB-based regimen, with dose increases and add-on therapies allowed in both arms to achieve optimal blood pressure-lowering efficacy. The primary study endpoint was a composite of defined cardio- and cerebrovascular events including stroke, myocardial infarction, and hospitalisation for heart failure or angina.
Significant, double-digit blood pressure reductions were observed in both treatment arms (133/76mmHg in both arms at study end). However, compared to the non-ARB-based therapy group, significantly fewer individuals in the Diovan add-on group experienced a primary endpoint (HR=0.55, p=0.00001). The reduction in the composite primary endpoint was largely due to a 45% reduction observed in the risk of stroke (HR=0.55, p=0.0149) and a 49% reduction in the risk of angina (HR=0.51, p=0.0106). Importantly, the number of adverse events was low overall, and there was no significant difference in tolerability between the two treatment groups.
The KYOTO HEART study was conceived, designed and conducted by an independent steering committee representing the Kyoto Prefectural University School of Medicine, and was funded by the Kyoto Foundation for the Promotion of Medical Science. Novartis Pharmaceuticals Canada had no role in the study’s conception or design, or in carrying out the study, including data collection, data analysis, data planning or data interpretation, or in the writing of the study report.
Novartis Pharma K K Japan has already made several research grants to the Kyoto Prefectural University School of Medicine.
More details on Diovan
The results from KYOTO HEART extend the existing wealth of evidence from multiple studies and patient populations of the clinical value of Diovan, which remains the only ARB indicated in Canada for post-myocardial infarction and heart failure patients, in addition to its proven powerful blood pressure lowering efficacy. An additional, large-scale outcomes study – NAVIGATOR – is currently ongoing which will assess whether Diovan or the oral antidiabetic nateglinide can reduce the incidence of cardiovascular events and reduce and delay the progression to clinical diabetes in patients with impaired glucose tolerance or ‘pre-diabetes’ at high risk of cardiovascular events.
Approved in Canada in 1997, Diovan is a selective ARB, and is indicated for the treatment of mild to moderate essential hypertension. Diovan may be administered alone, or in combination with thiazide diuretics or as a fixed dose combination called Diovan-HCT. Diovan is also approved to reduce cardiovascular mortality in clinically stable patients with signs and symptoms of left ventricular dysfunction in conjunction with acute myocardial infarction when the use of an angiotensin-converting enzyme inhibitor (ACEI) is not appropriate. Diovan is also approved for use in patients with chronic heart failure who have been shown to be intolerant to an angiotensin converting enzyme inhibitor.
There is no evidence that Diovan provides added benefits when it is used with ACE inhibitors. Diovan is not approved to reduce the risk of stroke or angina pectoris.