Jikei Heart Study - Jikei Heart Study

Description:

RETRACTION: The editors of the European Heart Journal have retracted the article reporting data/results of the Jikei 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 treatment with usual care plus the angiotensin II receptor blocker (ARB) valsartan compared with usual care alone among Japanese patients with heart failure, ischemic heart disease, or hypertension.

Hypothesis:

Valsartan will improve morbidity and mortality when added to conventional therapy.

Study Design

  • Randomized

Patients Enrolled: 3,081
Mean Follow Up: 3 years
Mean Patient Age: Mean age 65 years
Female: 34

Patient Populations:

Age 20 to 79 years and either: 1) essential hypertension diagnosed ≥3 months prior to enrollment, and actively receiving antihypertensive treatment, or 2) ischemic heart disease (newly developed or history of), or 3) heart failure (New York Heart Association classes II–IV) treated for ≥4 weeks

Primary Endpoints:

Onset of any cardiovascular event

Secondary Endpoints:

Death, changes in left ventricular size and function, renal function, changes in neurohormonal levels, and quality-of-life assessments

Drug/Procedures Used:

Following a run-in phase with non-ARB conventional therapy, patients in Japan were randomized to usual care plus valsartan (80 mg/d, titrated to 40-160 mg/d) (n = 1,541) or usual care alone (n = 1,540). ARBs including valsartan were not permitted in the usual care group, but other medications were at the discretion of the investigator. Patients were stratified by presenting syndrome (heart failure, ischemic heart disease, or hypertension).

Principal Findings:

Mean baseline systolic blood pressure was 139 mm Hg. Hypertension was present in 88% of patients at baseline, coronary heart disease in 33%, and heart failure in 11%. Medications at baseline included angiotensin-converting enzyme inhibitors (36%), beta-blockers (32%), and calcium channel blockers (68%). The average dose of valsartan during the study was 75 mg/d.

The trial was discontinued early at the recommendation of the Data Safety Monitoring Committee due to evidence of benefit. Blood pressure at follow-up was reduced by 8.2 mm Hg/4.7 mm Hg in the valsartan group and 7.2 mm Hg/3.7 mm Hg in the control group. The primary endpoint of any cardiovascular event was significantly lower in the valsartan group compared with the control group (hazard ratio [HR] 0.61, p = 0.00021). Among the components of the composite endpoint, stroke was lower in valsartan group (HR 0.60, p = 0.028), as was heart failure hospitalizations (HR 0.54, p = 0.029) and angina hospitalizations (HR 0.35, p < 0.0001). There was no difference in mortality (all-cause or cardiovascular) or in myocardial infarction.

Interpretation:

Among Japanese patients with heart failure, ischemic heart disease, or hypertension, addition of valsartan to usual care was associated with a reduction in the primary composite endpoint of cardiovascular events compared with usual care alone at a median 3-year follow-up.

The benefit seen with the reduction in cardiovascular events in the valsartan group cannot be fully explained by the blood pressure reduction, which was only minimally larger than in the usual care group (8.2/4.7 mm Hg vs. 7.2/3.7 mm Hg), suggesting another mechanism of action with valsartan. The overall results were noteworthy, but several questions remain including what medications were used in the control group and whether the results were similar for each of the three presenting syndromes (heart failure, ischemic heart disease, and hypertension).

References:

The Lancet Editors. Retraction—Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 2013;382:843.

Mochizuki S, Dahlöf B, Shimizu M, et al. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet. 2007 Apr 28;369(9571):1431-9.

Presented by B. Dahlof and S. Mochizuki, European Society of Cardiology Scientific Congress, September 2006.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Angiotensin Receptor Antagonists, Stroke, Myocardial Infarction, Follow-Up Studies, Valine, Tetrazoles, Calcium Channel Blockers, Angiotensin II Type 1 Receptor Blockers, Research Personnel, Heart Failure, Hypertension


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