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

Phase 4

Completed

Conditions: Hypertension
Ischemic Heart Disease
Congestive Heart Failure
Stroke

Interventions: Drug: Non-ARB
Drug: Valsartan

Registration Number: NCT00149227

Lead Sponsor: Kyoto Prefectural University of Medicine

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3031

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.)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-ARB	Non-ARB	'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs
Valsartan	Valsartan	Valsartan add-on treatment

Primary Outcome Measures

Name	Time	Method
New Onset or Recurrence of Stroke	five years	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	five years	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	five years	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	five years	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	five years	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	five years
New Onset of Acute Dissecting Aneurysm of the Aorta	five years	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	five years	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	five years	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.

Secondary Outcome Measures

Name	Time	Method
All Cause Mortality	five years
Worsening of Cardiac Function	five years
New Onset or Worsening of Arrhythmias	five years
New Onset or Worsening of Diabetes Mellitus or IGT	five years	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.	five years