Add-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)

• New Onset or Recurrence of Stroke [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• New Onset or Recurrence of Transient Ischemic Attack [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• New Onset or Recurrence of Acute Myocardial Infarction [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• 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 [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• 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 [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• Operation of PCI or Bypass Operation [ Time Frame: five years ] [ Designated as safety issue: No ]
  
• New Onset of Acute Dissecting Aneurysm of the Aorta [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• New Onset, Recurrence or Worsening of Arteriosclerosis Obliterans [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• Transition to Dialysis, Doubling of Plasma Cr Levels [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  

• All Cause Mortality [ Time Frame: five years ] [ Designated as safety issue: No ]
  
• Worsening of Cardiac Function [ Time Frame: five years ] [ Designated as safety issue: No ]
  
• New Onset or Worsening of Arrhythmias [ Time Frame: five years ] [ Designated as safety issue: No ]
  
• New Onset or Worsening of Diabetes Mellitus or IGT [ Time Frame: five years ] [ Designated as safety issue: No ]
  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.
  
  
• Uncontrolled Blood Pressure, Etc. [ Time Frame: five years ] [ Designated as safety issue: No ]
  

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.