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KYOTO HEART Study - KYOTO HEART Study
Description:
RETRACTION: The editors of the European Heart Journal have retracted the article reporting data/results of the KYOTO HEART Study, and discourage citations of it. Critical problems existed with some of the data reported in the paper.
The goal of the trial was to evaluate the efficacy of add-on valsartan therapy in addition to conventional treatment compared with conventional treatment without an ARB among Japanese patients with uncontrolled hypertension and one or more cardiovascular risk factors.
Hypothesis:
Addition of the angiotensin receptor blocker (ARB) valsartan on top of conventional treatment will be associated with a reduction in cardiovascular events compared with conventional treatment alone without an ARB among Japanese patients with uncontrolled hypertension and one or more cardiovascular risk factors.
Study Design
Patients Enrolled: 3031
Mean Follow Up: Median 3.27 years
Mean Patient Age: Mean age 66 years
Female: 43
Mean Ejection Fraction: Mean 63%
Patient Populations:
Japanese hypertensive patients whose blood pressures had been uncontrolled for at least 4 weeks (SBP ≥140 mm Hg and/or DBP ≥90 mm Hg) with one or more of the following risk factors: diabetes, smoking, lipid metabolism abnormality, history of CAD or CVD >6 months prior to screening, BMI ≥25, left ventricular hypertrophy on ECG
Exclusions:
Treated with ARB before randomization, history of worsening heart failure, unstable angina, MI, PCI, or CABG within the preceding 6 months
Primary Endpoints:
Composite of stroke, TIA, acute MI, angina, new or worsening heart failure, aorta aneurysm dissection, lower limb arterial obstruction, emergency thrombosis, transition to dialysis, and doubling of plasma Cr levels.
Secondary Endpoints:
All-cause mortality, worsening of cardiac function, new occurrence or exacerbation of arrhythmias, new occurrence or exacerbation of diabetes mellitus or impaired glucose tolerance, and uncontrolled blood pressure
Drug/Procedures Used:
Patients were randomized in an open-label manner to valsartan plus usual therapy (n = 1517) with the initial dose of 40-80 mg titrated up to 160 mg or conventional therapy without an ACE-inhibitor or ARB (n = 1514). Endpoints were adjudicated by an event committee blinded to treatment assignment.
Principal Findings:
At baseline, calcium channel blockers were used in 54-55% of patients, beta-blockers in 17-18%, and ACE-inhibitors in 19-20%. In the conventional therapy group at 12 months, calcium channel blocker use increased to 63% and beta-blockers to 21%. Mean blood pressure at baseline was 157/88 mm Hg. During the study period, mean blood pressure was reduced to 133/76 mm Hg in both groups, with no difference in blood pressure between the randomization arms. The blood pressure reduction was evident by 12 months and maintained throughout the study follow-up.
The primary composite endpoint of cardiovascular events was significantly lower in the valsartan plus conventional therapy group compared with the non-ARB conventional therapy group (5.5% vs 10.2%, hazard ratio [HR] 0.55, 95% CI 0.42-0.72, p<0.001). Among the components of the composite endpoint, there was a significant reduction in stroke/TIA (HR 0.55, 95% CI 0.34-0.89, p=0.015) and angina (HR 0.51, 95% CI
0.31-0.86, p=0.01); other components did not differ, including MI (0.5% in the valsartan group vs 0.7%, HR 0.65, 95% CI 0.2-1.8, p=0.39). New onset diabetes occurred less frequently in the valsartan add-on group (n=56 vs n=86, p=0.028). There was no difference in all-cause mortality (p=0.33) or CV death (p=0.37). There was also no difference between the groups in adverse events (3.2% vs 3.8%), which were infrequent in both arms.
Interpretation:
Among Japanese patients with uncontrolled hypertension and one or more cardiovascular risk factors, treatment with add-on valsartan therapy in addition to conventional treatment was associated with a reduction in the primary composite endpoint of cardiovascular events at a median follow-up of 3.3 years compared with conventional treatment without an ARB. The reduction in the primary endpoint was driven by angina and stroke, with no difference between groups in MI.
Several previous trials have shown mixed results for benefit with ARB add-on therapy. These trials have generally enrolled few Japanese patients. Cardiovascular disease differs in Japanese patients, with generally less fatal cardiac disease and more fatal stroke. The results of the present study are similar to those of the JIKEI-Heart Study, which studied the effect of add-on valsartan therapy in Japanese hypertensive patients and showed a reduction in cardiovascular events with valsartan add-on compared to non-ARB add-on therapy. HIJ-CREATE, another large ARB trial of Japanese hypertensive patients, did not show a significant difference with candesartan therapy, suggesting that there may be differences in treatment effect within the ARB class. Alternatively, variation in study design may also explain part of the differences in the results.
References:
Sawada T, Yamada H, Dahlöf B, Matsubara H. Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J 2009;30:2461-9.
Presented by Dr. Hiroaki Matsubara at the European Society of Cardiology Congress, Barcelona, Spain, September 2009.
Keywords: Hypertrophy, Left Ventricular, Angiotensin Receptor Antagonists, Stroke, Follow-Up Studies, Lipid Metabolism, Risk Factors, Electrocardiography, Valine, Tetrazoles, Calcium Channel Blockers, Smoking, Body Mass Index, Angiotensin II Type 1 Receptor Blockers, Benzimidazoles, Hypertension, Diabetes Mellitus
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