Administration Time-dependent Antihypertensive Effects of Low Dose Aspirin in Well-controlled Hypertensive Patients

A Multi-center, Double-Blind Randomized, Cross-over, Active-control, Comparative Clinical Study to Evaluate the Administration Time-dependent Antihypertensive Effects of Low Dose Aspirin in Well-Controlled Hypertensive Patients (Phase IV)

The purpose of this study is to evaluate the influence of aspirin on blood pressure in well-controlled hypertensive patients who receive low dose aspirin at different times of the day

Recent studies showed that low dose aspirin exerts a significant administration time-dependent effect on blood pressure in previously untreated hypertensive patients. However, this effect has not been confirmed in patients taking low-dose aspirin in combination with antihypertensive medications. A multi-center, double-blind randomized, cross-over, active-control, comparative clinical study will be conducted to evaluate the influence of aspirin on blood pressure in well-controlled hypertensive patients who receive low dose aspirin at different times of the day.

Approximately 192 patients will be enrolled over 4 months in 8 centers nationwide.

After placebo run-in period, all subjects will be randomized into one of the following 3 groups.

Group I & II will take low dose aspirin for treatment period (for first and second 12 weeks)on awakening or before bed time. Group III will take placebo for treatment period.

After first 12 weeks' treatment period, the subjects will be informed whether she/he belongs to Group III. This will be done without breaking the double blinding in the other 2 groups.

The primary objective will be the evaluation of the influence of aspirin on blood pressure in well-controlled hypertensive patients who receive low dose aspirin at different times of the day.

The secondary objectives will be 1) comparison of the administration time-dependent effects of low dose aspirin on blood pressure between dipper and non-dipper patients and 2) the evaluation of the effects of low dose aspirin in Korean hypertensive patients.

A sub-study will be conducted in 3 centers to evaluate the effect of aspirin on endothelial function in patients with well-controlled hypertension.

Inclusion Criteria:

• Age : 30 - 70 (inclusive)
• Essential hypertension without complication
• Well-controlled blood pressure over 3 months with same antihypertensive medication without changes in dose and frequency
• Averages of two consecutive sitting diastolic and systolic blood pressures are <90 mmHg and <140 mmHg, respectively at screening and visit 1
• Differences in sitting diastolic and systolic blood pressures between screening and visit 1 are 10 mmHg and 20 mmHg, respectively.
• Willing and able to give informed consent

Exclusion Criteria:

• patients with sitting diastolic blood pressure < 70 mmHg
• patients with secondary or malignant hypertension
• patients with complication or high risk of complication
• proven coronary artery or peripheral vascular diseases
• Framingham CHD Risk Score (10 years) 20
• Fasting blood glucose 110 mg/dl
• Hyperlipidemia under treatment or treatment required
• patients with myocardial infarction or severe cerebrovascular disorder in last 6 months
• patients with chronic renal insufficiency
• patients with unstable angina
• patients with severe left ventricular abnormalities or valvular defect
• patients with bradycardia(pulse rate < 50 times/min) or chronic tachycardia (pulse rate 100 times/min), second degree AV-block
• SGOT, SGPT> 2.5 times upper limit range or serum creatinine > 1.5 times upper limit range
• patients with unresolved malignant tumor or systemic infection
• lactating or pregnant females or females of childbearing potential who do not undergo hysterectomy or are not willing to use "effective" method of contraception.
• known hypersensitivities to the investigational drug
• patients judged to have alcohol or other drug abuse by the investigator
• patients who takes contraindicated drug at study entry (visit 1) or needs to contraindicated drug throughout the study period(if judged by the investigator not to influence on the study due to the temporal administration etc.)
• patients judged to be inappropriate for this study be the investigator
• patients with gastrointestinal troubles to NSAIDs