Rosuvastatin Effect on Serial Echocardiographic Measurement of Coronary Flow Velocity Reserve

Hypertension Clinical Trial

— RESERVE  

Official title:

Effect of Rosuvastatin on Coronary Flow Reserve in Hypertensive Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01490398
• Other study ID #: 2011-0865
• Status: Completed
• Phase: Phase 4
• First received: December 9, 2011
• Last updated: May 8, 2014
• Start date: December 2011
• Est. completion date: October 2013

Study information

• Verified date: May 2014
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

In ASCOT study, lipid lowering with a statin provided additional beneficial effects in hypertensive patients with average levels of serum total cholesterol. However, the underlying mechanism of statins to improve clinical outcomes in hypertension is unclear and the effect of statins on coronary flow reserve (CFR) has not been examined in hypertensive patients. Therefore, it is clinically important and timely project to measure CFR non-invasively using echocardiography and to elucidate the mechanism of clinical benefits of statins in hypertensive patients with cardiovascular risk. The investigators try to evaluate the effect of rosuvastatin on CFR by measuring the change of CFR after 1 year treatment of rosuvastatin, and to correlate CFR with LDL-cholesterol and CRP.

Description:

In hypertensive patients with high risk, lipid lowering with a statin provided additional beneficial effects in hypertensive patients with average levels of serum total cholesterol. However, the underlying mechanism of statins to improve clinical outcomes in hypertension is unclear. In patients with hypercholesterolemia or coronary atherosclerosis, several studies reported that level of LDL-cholesterol was inversely correlated with coronary blood flow reserve and suggested that statin improved coronary blood flow. Although it is speculated that statin may improve coronary blood flow by decreasing LDL cholesterol level and stabilizing atherosclerotic plaque in coronary atherosclerosis, the effect of statins on coronary flow reserve (CFR) has not been examined in hypertensive patients.

LDL cholesterol is expected to significantly decrease when rosuvastatin 20mg is administered. In addition to LDL-cholesterol lowering effect, the stabilization of atherosclerotic plaque and the regression of atheroma are observed during rosuvastatin treatment. Because of these beneficial effects of rosuvastatin, it may be expected that rosuvastatin will improve coronary blood flow even in hypertensive patients without hypercholesterolemia and the efficacy of rosuvastatin on CFR needs to be investigated in hypertensive patients with cardiovascular risk.

Morphologic assessment for the measurement of coronary lumen in the invasive coronary angiography is used as a gold standard to assess the stenosis in coronary diseases. However, as decrease of myocardial blood flow due to coronary artery disease could not be exactly evaluated by morphologic stenosis, the functional test was required to assess the significance of coronary artery stenosis, and CFR could be directly measured using Doppler guide wire since mid-1990s. Since the pathophysiological implication of coronary stenosis can be assessed using CFR measurement, CFR value is widely used in clinical practice as a very useful indicator to assess coronary stenosis severity in performing percutaneous coronary intervention. As a high frequency transducer with excellent resolution has been used, coronary artery can be directly imaged, and coronary flow velocity can be measured using echo-Doppler technique. As a result, CFR is easily measured in an echocardiography lab which could be measured only in a cardiac catheterization lab using Doppler guide wire in the past. It was confirmed that CFR values obtained by Doppler technique were same as those invasively obtained in a cardiac catheterization lab. The clinical usefulness and accuracy of the technique have been verified also in the diagnosis of coronary artery disease.

Therefore, it is clinically important and timely project to measure CFR non-invasively using echocardiography and to elucidate the mechanism of clinical benefits of statins in hypertensive patients with cardiovascular risk. We try to evaluate the effect of rosuvastatin on CFR by measuring the change of CFR after 1 year treatment of rosuvastatin, and to correlate CFR with LDL-cholesterol and CRP.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

Inclusion Criteria:

• Controlled Hypertension: treated SBP < 140 mmHg and DBP < 90 mmHg

• LDL cholesterol > 130 mg/dL

• Patients with statin-naive state, defined as receiving no statin therapy for more than 3 months during the previous 12 months

• Any 1 of these cardiovascular risk factors required: smoking, Type 2 DM, age over 55 (men) or 65 (women), peripheral vascular disease, 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, Transient ischemic attack < 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 respiratory, hematological, gastrointestinal, hepatic, renal or other disease

• Pregnant or lactating women and those of child-bearing potential

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Risk Factors
• Hypertension

Intervention

Drug:
• Rosuvastatin
After baseline assessment, the starting dose of rosuvastatin 10 mg will be given to study patients. If tolerated and LDL-C is > 100mg/dL after 2-4 weeks, the dose will be increased to 20 mg. Rosuvastatin treatment is scheduled to continue for 1 year without no further dose titration, and each patient will be followed at 2 months, 6 months and 1 year.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	AstraZeneca

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of coronary flow velocity reserve	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	No
Secondary	Change of averaged peak diastolic velocity	Change of averaged peak diastolic velocity from baseline to study end.	12 months	No
Secondary	Change of CRP	Change of CRP from baseline to study end.	12 months	No
Secondary	Change of LDL cholesterol	Change of LDL cholesterol from baseline to study end.	12 months	No