Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study.
BACKGROUND
Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease. However, evidence for this effect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease.


METHODS
We initiated a multicentre, prospective, randomised controlled trial of 3081 Japanese patients, aged 20-79 years, (mean 65 [SD 10] years) who were undergoing conventional treatment for hypertension, coronary heart disease, heart failure, or a combination of these disorders. In addition to conventional treatment, patients were assigned either to valsartan (40-160 mg per day) or to other treatment without angiotensin receptor blockers. Our primary endpoint was a composite of cardiovascular morbidity and mortality. Analysis was by intention to treat. The study was registered at clintrials.gov with the identifier NCT00133328.


RESULTS
After a median follow-up of 3.1 years (range 1-3.9) the primary endpoint was recorded in fewer individuals given valsartan than in controls (92 vs 149; absolute risk 21.3 vs 34.5 per 1000 patient years; hazard ratio 0.61, 95% CI 0.47-0.79, p=0.0002). This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack (29 vs 48; 0.60, 0.38-0.95, p=0.028), angina pectoris (19 vs 53; 0.35, 0.20-0.58, p<0.0001), and heart failure (19 vs 36; 0.53, 0.31-0.94, p=0.029) in those given valsartan than in the control group. Mortality or tolerability did not differ between groups.


CONCLUSIONS
The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment. These benefits cannot be entirely explained by a difference in blood pressure control.
Mochizuki
Seibu
S
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. Electronic address: m_seibu@jikei.ac.jp.
Dahlöf
Björn
B
Institute of Medicine, Department of Emergency and Cardiovascular Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden.
Shimizu
Mitsuyuki
M
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Ikewaki
Katsunori
K
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Yoshikawa
Makoto
M
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Taniguchi
Ikuo
I
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Ohta
Makoto
M
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Yamada
Taku
T
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Ogawa
Kazuhiko
K
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Kanae
Kiyoshi
K
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Kawai
Makoto
M
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Seki
Shingo
S
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Okazaki
Fumiko
F
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Taniguchi
Masayuki
M
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Yoshida
Satoru
S
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Tajima
Naoko
N
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D007564:Japan; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine