Title

Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension
  • Phase

    Phase 4
  • Study Type

    Interventional
  • Intervention/Treatment

    valsartan ...
  • Study Participants

    3031
The KYOTO HEART Study is to assess the add-on effect of valsartan, an Angiotensin-Receptor Blocker, on top of the conventional treatment in high risk patients in Japan with hypertension in terms of the morbidity and mortality.
Although many reports show that ACE inhibitors and angiotensin II receptor blockers (ARB) are superior for prevention of cardiovascular events, previous data are not enough for the patients who have more than one risk factor and for anti-atherosclerotic effects of ARB. In Japan, there were only a few large-scale trials for cardiovascular disease prevention, and it has not been clarified whether the evidence in Western countries could be unqualifiedly applied to Japanese patients as a long-range strategy. The KYOTO HEART Study is to assess the add-on effect of valsartan, an Angiotensin-Receptor Blocker, on top of the conventional treatment in high risk patients with hypertension in terms of the morbidity and mortality.
Study Started
Jan 31
2004
Primary Completion
Jan 31
2009
Study Completion
Jan 31
2009
Results Posted
Dec 12
2012
Estimate
Last Update
Dec 12
2012
Estimate

Drug Valsartan

Valsartan add-on arm: valsartan 40-160 mg per day, and an additional antihypertensive drugs other than ARB and ACEI are administered if necessary.

  • Other names: Diovan

Drug Non-ARB

'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs

  • Other names: Conventional anti-hypertensive treatment

Non-ARB Active Comparator

'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs

Valsartan Experimental

Valsartan add-on treatment

Criteria

Inclusion Criteria:

Clinical diagnosis of hypertension
Clinical diagnosis of one or more risk factors, such as diabetes, smoking habit, lipid metabolism abnormality, history of ischemic heart disease (IHD) or cerebrovascular disease, obesity (BMI>25), chronic heart failure (NYHA II-III), and electrocardiogram (ECG) abnormality (LVH)

Exclusion Criteria:

Patients who have already been administered ARB
Patients with IHD within 6 months after percutaneous coronary intervention(PCI), and who are stable but are going to implement PCI or coronary artery bypass grafting(CABG)
Severe/malignant/secondary hypertensive patients
Pregnant women and women of childbearing potential
History of heart failure, unstable angina, myocardial infarction, PTCA, or CABG within the preceding 6 months
Arrhythmia needed to be treated or accompanied with symptoms, second or third degree AV block
Severe renal impairment (Serum creatinine >3.0 mg/dl)
Severe hepatic impairment (Hepatic failure, Cirrhosis, etc.)

Summary

Valsartan

Non-ARB

All Events

Event Type Organ System Event Term

New Onset or Recurrence of Stroke

Stroke events included brain hemorrhage, infarction, and TIA. They required hospitalization with neurological symptoms and were diagnosed by CT and/or MRI. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

25.0
event number

Non-ARB

46.0
event number

New Onset or Recurrence of Transient Ischemic Attack

Transient ischemic attack (TIA) was defined as hospitalization with sudden onset of neurological deficit persisting for less than 24 hrs, and without abnormal findings using by CT and/or MRI. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

6.0
event number

Non-ARB

4.0
event number

New Onset or Recurrence of Acute Myocardial Infarction

Acute myocardial infarction was diagnosed with hospitalization, ECG- change, and biomarkers for myocardial infarction. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

7.0
event number

Non-ARB

11.0
event number

Hospitalization Due to the New Onset, Recurrence or Worsening of Heart Failure and Additional Concomitant Use of Other Anti-heart Failure Agents or Increase of Dosage

Heart failure event was defined as requiring hospitalization and clinical symptoms together with left ventricular dysfunction by echocardiography according to the guidelines of the AHA/ACC. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

12.0
event number

Non-ARB

26.0
event number

Hospitalization Due to the New Onset, Occurrence or Worsening of Angina Pectoris and Additional Concomitant Use of Other Anti-anginal Agents or Increase of Dosage

Angina pectoris event required hospitalization and was diagnosed by both ECG changes corresponding with chest symptoms and coronary angiography showing 75% stenosis according to AHA/ACC guidelines. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Non-ARB

44.0
event number

Valsartan

22.0
event number

Operation of PCI or Bypass Operation

Outcome Measure Data Not Reported

New Onset of Acute Dissecting Aneurysm of the Aorta

Dissecting aneurysm of the aorta required hospitalization and was diagnosed by imaging technique, CT and/or MRI. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

3.0
event number

Non-ARB

5.0
event number

New Onset, Recurrence or Worsening of Arteriosclerosis Obliterans

Arteriosclerosis obliterans (ASO) event was diagnosed with symptoms and CT / MRI imaging. The first of any of these events to occur in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

11.0
event number

Non-ARB

12.0
event number

Transition to Dialysis, Doubling of Plasma Cr Levels

The first of any events, "transition to dialysis" or "doubling of plasma Cr levels compared to the entry", occurring in a specific patient was classified as an event to be counted in the primary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

6.0
event number

Non-ARB

14.0
event number

All Cause Mortality

Valsartan

22.0
patients

Non-ARB

32.0
patients

Worsening of Cardiac Function

Outcome Measure Data Not Reported

New Onset or Worsening of Arrhythmias

Outcome Measure Data Not Reported

New Onset or Worsening of Diabetes Mellitus or IGT

Diabetes mellitus was defined as fasting plasma glucose >=126 mg/dl, causal blood glucose >= 200 mg /dl, HbA1C >= 6.5%, and/or plasma glucose 2hr after 75g glucose load >= 200 mg/dl. The first of these events, "new onset diabetes" or "worsening diabetes following IGT", occurring in a specific patient was classified as an event to be counted in the secondary endpoint by the Endpoint Committee. We estimated the number of enrolled patients to validate the hypothesis under the assumption that the valsartan add-on group achieves a 20% risk reduction compared with the conventional treatment group and gives 80% statistical power for detecting a clinical significance with a two-tailed 5% statistical significant level.

Valsartan

58.0
event number

Non-ARB

86.0
event number

Uncontrolled Blood Pressure, Etc.

Outcome Measure Data Not Reported

Total

3031
Participants

Age Continuous

65.9
years (Mean)
Standard Deviation: 11.1

Region of Enrollment

Sex: Female, Male

Overall Study

Valsartan

Non-ARB