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

Add-on Effects of Valsartan on Morbi- Mortality in High Risk Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Stroke; Hypertension; Ischemic Heart Disease; Congestive Heart Failure
• Intervention / Treatment: Drug: Non-ARB; Drug: Valsartan

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.

• Study Type: Interventional
• Enrollment (Actual): 3031
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 602-8566
    • Kyoto Prefectural University of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non-ARB; 'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs	Drug: Non-ARB; 'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs; Other Names: Conventional anti-hypertensive treatment
Experimental: Valsartan; Valsartan add-on treatment	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	five years
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.	five years
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.	five years
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.	five years
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.	five years
Operation of PCI or Bypass Operation		five years
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.	five years
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.	five years
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.	five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	five years
Uncontrolled Blood Pressure, Etc.		five years

Collaborators and Investigators

• Sponsor: Kyoto Prefectural University of Medicine
• Investigators: Study Chair: Hiroaki Matsubara, MD,PhD, Kyoto Prefectural University of Medicine

Publications and helpful links

General Publications

• Sawada T, Takahashi T, Yamada H, Dahlof B, Matsubara H; KYOTO HEART Study Group. Rationale and design of the KYOTO HEART study: effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high risk of cardiovascular events. J Hum Hypertens. 2009 Mar;23(3):188-95. doi: 10.1038/jhh.2008.116. Epub 2008 Sep 18. Erratum In: J Hum Hypertens. 2013 Sep;27(9):580.
• Sawada T, Yamada H, Dahlof B, Matsubara H; KYOTO HEART Study Group. Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J. 2009 Oct;30(20):2461-9. doi: 10.1093/eurheartj/ehp363. Epub 2009 Aug 31.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 6, 2005
• First Posted (Estimate): September 8, 2005

Study Record Updates

• Last Update Posted (Estimate): December 12, 2012
• Last Update Submitted That Met QC Criteria: December 9, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Ischemic heart disease; High risk hypertension; Angiotensin receptor blockers; Cardiovascular mortality- morbidity; KYOTO HEART Study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Failure; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Hypertension; Molecular Mechanisms of Pharmacological Action; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Antihypertensive Agents
• Other Study ID Numbers: KHS2004