Effect of Pitavastatin on Coronary Flow Reserve in Hypertensive Patients

Study Overview
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Brief Summary
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Although statins reduce cardiac events in hypertensive patients with cardiovascular risk factors, the effect of statins on coronary flow reserve (CFR) has not been examined in such patients. The investigators hypothesize that pitavastatin added to standard antihypertensive therapy will be superior to placebo in improving CFR in hypertensive patients with cardiovascular risk, and try to examine this hypothesis in a double-blind, randomized comparison study using Doppler echocardiography.

Detailed Description
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Statin treatment improves coronary flow reserve (CFR) and decreases cardiac morbidity and mortality in patients with coronary artery disease (CAD) and hypercholesterolemia. Endothelial dysfunction and impairment in coronary microcirculation is also observed in hypertensive patients with cardiovascular risk factors. However, the measurement of CFR has rarely been performed in hypertensive patients without CAD, because CFR could be invasively measured using a Doppler guide wire in a cardiac catheterization laboratory. Recent advances in echocardiographic imaging techniques have made it possible to measure coronary flow velocity and CFR, which highly correlates with the CFR measured by invasive means. Lipid lowering with a statin provided beneficial effects in patients with average levels of serum total cholesterol in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) study conducted in hypertensive patients at cardiovascular risk. Improvements in endothelial dysfunction and CFR may be related to the beneficial effects of statins in hypertensive patients without hypercholesterolemia, but the effect of statins on CFR has not been examined in such patients. Accordingly, the investigators try to examine the hypothesis that pitavastatin added to standard antihypertensive therapy in hypertensive patients with cardiovascular risk will be superior to placebo in improving CFR in a double-blind, randomized comparison study using Doppler echocardiography.

Official Title
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Effect of Pitavastatin on Coronary Flow Reserve in Hypertensive Patients With Cardiovascular Risk

Conditions
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Hypertension, Cardiovascular Risk

Intervention / Treatment
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* Drug: Pitavastatin
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Controlled Hypertension: treated SBP<140 mmHg and DBP<90 mmHg LDL cholesterol ≥ 130mg/dL Patients with statin-naive state, defined as receiving no statin therapy for more than 6 months during the previous 12 months. Any 1 of these cardiovascular risk factors required: smoking, age over 55 (men) or 65 (women), history of cerebrovascular event, family history of early CHD before age 55, HDL cholesterol < 40 mg/dL Exclusion Criteria: A previous history of intolerance or hypersensitivity to statins Uncontrolled hypertension; SBP≥140 mmHg or DBP≥90 mmHg Previous MI or currently treated angina pectoris Stroke, TIA < 3 months Secondary hypertension Fasting serum triglyceride > 500 mg/dL Clinical congestive heart failure Uncontrolled arrhythmia Left ventricular hypertrophy: LV mass index >134g/m2 (male) or >110g/m2 (female) Concomitant clinically important hematological, gastrointestinal, hepatic, renal or other disease Pregnant or lactating women and those of child-bearing potential Diabetes Peripheral vascular disease Unwillingness or inability to comply with the procedures described in this protocol

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Patients continue taking their antihypertensive medication alone. | Other: Control<br>* Life style modification alone<br>|
| Active Comparator: Pitavastatin<br>Pitavastatin 4 mg is given to study patients after a baseline assessment and continued for 1 year without further dose titration. Patients continue taking their antihypertensive medication during the entire follow-up period. | Drug: Pitavastatin<br>* statin<br>* Other names: Livalo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the CFR value | Change of coronary flow velocity reserve from baseline to 1 year follow-up. For each patient, the averaged value of coronary flow velocity reserve will be obtained at baseline and 1 year follow-up. | 12 months | 
| Difference in mean CFR value | DIfference in CFR value at 12 month follow-up between pitavastatin and placebo arm | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of CRP | Change of CRP from baseline to 1 year follow-up. | 12 months | 
| Change of LDL-cholesterol | Change of LDL-cholesterol from baseline to 1 year follow-up. | 12 months | 
| Change of averaged peak diastolic velocity | Change of averaged peak diastolic velocity from baseline to study end. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Statin