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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-ARB | Active Comparator | 'Non-ARB' was defined as Conventional anti-hypertensive treatment except for ARB and ACEIs |
|
| Valsartan | Experimental | Valsartan add-on treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Valsartan | Drug | Valsartan add-on arm: valsartan 40-160 mg per day, and an additional antihypertensive drugs other than ARB and ACEI are administered if necessary. |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| All Cause Mortality | five years | |
| Worsening of Cardiac Function | five years | |
| New Onset or Worsening of Arrhythmias |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hiroaki Matsubara, MD,PhD | Kyoto Prefectural University of Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kyoto Prefectural University of Medicine | Kyoto | Kyoto | 602-8566 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18800142 | Background | 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. | |
| 19723695 |
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Among 3042 patients eligible, 4 patients were withdrawn due to refusal of informed consent, 7 were withdrawn due to incompatible object. Finally, 3031 patients were assigned to the treatment groups.
We recruited patients between January 2004 and June 2007. Participating centres included 31 associated hospitals led by physicians (cardiology specialists) from Kyoto Prefectural University School of Medicine.
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| ID | Title | Description |
|---|---|---|
| FG000 | Valsartan | For the valsartan add-on group, valsartan 80 mg once daily in the morning was administered to the patient as an initial dose, the dose was doubled after 4 weeks if the initial dose could not achieve the target blood pressure of less than 140/90 mmHg (in patients with diabetes or renal disease, target blood pressure was set to less than 130/80 mmHg). After 8 weeks, an additional administration of other antihypertensive drugs with flexible dosing regimen other than ARBs and ACE inhibitors was allowed if necessary. |
| FG001 | Non-ARB | For the conventional treatment group, the anti-hypertensive drugs other than ARB and ACE inhibitors were provided for the patients to reach the target blood pressure. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Valsartan | For the valsartan add-on group, valsartan 80 mg once daily in the morning was administered to the patient as an initial dose, the dose was doubled after 4 weeks if the initial dose could not achieve the target blood pressure of less than 140/90 mmHg (in patients with diabetes or renal disease, target blood pressure was set to less than 130/80 mmHg). After 8 weeks, an additional administration of other antihypertensive drugs with flexible dosing regimen other than ARBs and ACE inhibitors was allowed if necessary. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Analyses were made by the independent Statistical Analysis Organization based on the intention-to-treat principle. | Posted | Number | event number | five years |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Valsartan | For the valsartan add-on group, valsartan 80 mg once daily in the morning was administered to the patient as an initial dose, the dose was doubled after 4 weeks if the initial dose could not achieve the target blood pressure of less than 140/90 mmHg (in patients with diabetes or renal disease, target blood pressure was set to less than 130/80 mmHg). After 8 weeks, an additional administration of other antihypertensive drugs with flexible dosing regimen other than ARBs and ACE inhibitors was allowed if necessary. |
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The study was performed using PROBE design, which does not exclude possible bias for softer endpoints such as angina and TIA. However, all softer endpoints were diagnosed by CAG and CT/MRI. We believe that under reporting would be unlikely.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Hiroaki Matsubara | Department of Cardiology, Kyoto Prefectural University of Medicine | +81-75-251-5511 | matsubah@koto.kpu-m.ac.jp |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D017202 | Myocardial Ischemia |
| D006333 | Heart Failure |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D002561 | Cerebrovascular Disorders |
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| ID | Term |
|---|---|
| D000068756 | Valsartan |
| ID | Term |
|---|---|
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Non-ARB | Drug | 'Non-ARB' was defined conventional anti-hypertensive treatment except for ACEIs and ARBs |
|
|
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 |
| 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 |
| 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. |
|
| BG001 | Non-ARB | For the conventional treatment group, the anti-hypertensive drugs other than ARB and ACE inhibitors were provided for the patients to reach the target blood pressure. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Non-ARB | For the conventional treatment group, the anti-hypertensive drugs other than ARB and ACE inhibitors were provided for the patients to reach the target blood pressure. |
|
|
|
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Primary | Operation of PCI or Bypass Operation | Not Posted | Number | event number | five years |
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Primary | 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. | Posted | Number | event number | five years |
|
|
|
| Secondary | All Cause Mortality | Posted | Number | patients | five years |
|
|
|
| Secondary | Worsening of Cardiac Function | Not Posted | Number | event number | five years |
| Secondary | New Onset or Worsening of Arrhythmias | Not Posted | Number | event number | five years |
| Secondary | 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. | Posted | Number | event number | five years |
|
|
|
| Secondary | Uncontrolled Blood Pressure, Etc. | Not Posted | Number | patients | five years |
| 0 |
| 1,517 |
| 0 |
| 1,517 |
| EG001 | Non-ARB | For the conventional treatment group, the anti-hypertensive drugs other than ARB and ACE inhibitors were provided for the patients to reach the target blood pressure. | 0 | 1,514 | 0 | 1,514 |
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014633 |
| Valine |
| D000597 | Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |