BARCELONA — Add-on valsartan for control of high-risk hypertension resulted in a highly significant 45% reduction in the incidence of the primary cardiovascular end point compared with non–angiotensin receptor blocker add-on therapy in the randomized Kyoto Heart Study.
The estimated number of patients who would need to be treated (NNT) with valsartan (Diovan) instead of an alternative antihypertensive drug for 3.27 years to prevent one additional adverse cardiovascular event was 21, Dr. Hiroaki Matsubara reported at the annual congress of the European Society of Cardio-logy.
The combined primary end point consisted of stroke, MI, angina, hospitalization for heart failure, coronary revascularization, renal failure, or peripheral artery disease. The overall 45% decrease in the valsartan group was driven chiefly by reductions of 55% in the risk of stroke and 49% for angina, noted Dr. Matsubara of Kyoto (Japan) Prefectural University School of Medicine.
The Kyoto Heart Study randomized 3,042 hypertensive Japanese subjects at high cardiovascular risk to open-label add-on valsartan or non-ARB antihypertensive therapy. High risk was defined by the presence of diabetes, ECG evidence of left ventricular hypertrophy, obesity, smoking, or a history of coronary artery disease. With add-on therapy, patients achieved identical blood pressure lowering, going from a mean baseline of 157/88 mm Hg to 133/76 mm Hg. Although the target dose for valsartan was 160 mg/day—the maximum in Japan—the average dose was 88 mg/day.
The trial was halted early, after a median 3.27 years of follow-up, for ethical reasons because the combined primary end point had been reached by 10.2% of control patients compared with 5.5% of those in the valsartan group.
There were 25 strokes in the valsartan arm, compared with 46 in controls. Moreover, the valsartan group had 22 cases of angina pectoris, as determined by a blinded end point committee on the basis of ECG evidence and confirmatory coronary angiography, compared with 44 cases in controls. The NNT to prevent one stroke was 72; the NNT to prevent one case of angina was 69.
New-onset diabetes, a prespecified secondary end point, occurred in 86 controls, compared with 58 valsartan-treated patients, a highly significant difference.
However, rates of MI, heart failure hospitalization, and all-cause mortality were not significantly different in the two treatment arms.
The Kyoto Heart Study was undertaken because of a dearth of clinical trial data on the use of ARBs in Asian patients. For example, Asians comprised less than 4% of participants in the landmark Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) and Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trials, and not a single Japanese patient was included in either of these very large studies, Dr. Matsubara noted.
Cardiovascular disease in the Japanese population differs from that in the United States and Europe. Cardiovascular mortality is one-third that in the United States; however, stroke mortality is at least 50% greater. The Japanese have a much lower average body mass index than do Americans, but their salt intake is 2.5-fold greater. While the prevalence of hypertension is comparable in Japan and the West, calcium channel blockers account for more than 60% of all antihypertensive drug prescriptions in Japan.
The Kyoto findings suggest valsartan may be considered a vascular-specific ARB. It has the greatest selectivity of any ARB for the angiotensin type-1 receptor, and it appears to be particularly useful in treating hypertensive patients who have angina or who are at risk for stroke, according to Dr. Matsubara.
The Kyoto Heart Study was funded by Kyoto Prefectural University. Dr. Matsubara reported having no financial conflicts of interest regarding their presentations.