2.JIKEI Heart Study(revised Edition)

The JIKEI Heart Study The largest cardiovascular intervention study in Asian population : 

The JIKEI Heart Study The largest cardiovascular intervention study in Asian population

Background : 

Background Drugs that inhibit the RAAS, such as the ARBs, have demonstrated clinical benefits in patients at risk for, or with existing, cardiovascular diseases Evidence of these benefits is largely lacking in Asian populations

The JIKEI HEART Study : 

The JIKEI HEART Study Investigator initiated and conducted Prospective, randomised, open-label, blinded end-point (PROBE) 3081 Japanese patients with high blood Pressure, coronary heart disease and/or heart failure Valsartan vs non-ARB-based therapy to achieve aggressive BP target of 130/80mm Hg FU 1-3.9 yr (median 3.1 yr)

Study hypothesis : 

Study hypothesis Study hypothesis Diovan will improve morbidity and mortality when added to conventional therapies in Japanese patients with hypertension and cardiovascular disease Primary endpoint Composite of CV mortality and morbidity Stroke or TIA, MI, Hospitalization for CHF or angina pectoris, dissecting aneurysm of the aorta, lower limb arterial obstruction, doubling of serum creatinine or transition to dialysis

Treatment schedule : 

Treatment schedule Run-In Conventional Treatment (Non ARB) + non ARB Diovan 80mg Diovan 40-160 mg + non ARB treatment arm + non ARB + non ARB + non ARB Diovan arm -4 week 0 week 8-12 week 12-16 week Screening Randomisation End of treatment titration titration

Treatment schedule : 

Treatment schedule

Slide 10: 

Lancet 2007

Blood pressure results : 

Blood pressure results

Unequivocal benefit : 

Unequivocal benefit On a recommendation from the DSMB (data safety monitoring board) the study was halted early for ethical reasons, after just over 3 years, due to unequivocal benefit from Valsartan

Primary endpoints : 

Primary endpoints Relative Risk Reduction 39% (95% CI: 0.47-0.79) months 343 368 657 689 1075 1092 1447 1441 Non ARB Valsartan 1540 1541 Valsartan arm 92 events Non- ARB arm 149 events Event rate (%) 0 5 10 15 0 12 24 36 48 HR=0.61,P=.00021 39% 344 368 835 855 1262 1257 1502 1505 6 18 30 42

New or recurrent stroke : 

New or recurrent stroke months Valsartan arm 29 events Non- ARB arm 48 events Event rate (%) 0 1.0 1.5 2.5 HR=0.60,P=.028 40% 2.0 0.5 343 368 657 689 1075 1092 1447 1441 Non ARB Valsartan 1540 1541 0 12 24 36 48 344 368 835 855 1262 1257 1502 1505 6 18 30 42 3.5 3.0 Relative Risk Reduction 40% (95% CI: 0.38-0.95)

Hospitalisation for Heart failure : 

Hospitalisation for Heart failure Relative Risk Reduction 46% (95% CI: 0.31-0.94) months Valsartan arm 19 events Non- ARB arm 36 events Event rate (%) 0 1.0 1.5 2.5 HR=0.54,P=.0029 46% 2.0 0.5 343 368 657 689 1075 1092 1447 1441 Non ARB Valsartan 1540 1541 0 12 24 36 48 344 368 835 855 1262 1257 1502 1505 6 18 30 42

Hospitalization for angina pectoris : 

Hospitalization for angina pectoris months Valsartan arm 19 events Non- ARB arm 53 events Event rate (%) 0 1 HR=0.35,P=.00007 65% 2 343 368 657 689 1075 1092 1447 1441 Non ARB Valsartan 1540 1541 0 12 24 36 48 344 368 835 855 1262 1257 1502 1505 6 18 30 42 4 3 Relative Risk Reduction 65% (95% CI: 0.20-0.58)

Effect of treatment on End Points : 

Effect of treatment on End Points 0.0002 0.0280 0.7515 0.0001 0.0293 0.0340 0.8966 0.7537 0.9545 Primary end points Composite endpoints Secondary endpoints Stroke or TIA MI Hospitalization for angina pectoris Hospitalization for heart failure Disconnecting aortic aneurysm Transition to dialysis, doubling serum Cr levels All cause mortality Cardiovascular mortality P Event .2 .4 .6 .8 1 1.2 Favors Diovan Favors non ARB

What did the study show? : 

What did the study show? “ An anthihypertensive regimen consisting of Valsartan added to conventional therapies improves morbidity and mortality in Japanese patients with hypertensions and cardiovascular disease.”

Clinical implications : 

Clinical implications For the first time, the clinical benefit of Diovan added to the benefits from blood pressure control, are extended to an Asian population The JIKEI Heart study results are highly relevant to clinical practice We have to consider not only aggressive blood pressure control but also which blood pressure drug is the best choice to prevent outcomes