Antihypertensive Effect and Safety of a Candesartan/Hydrochlorothiazide Combination in Patients with Uncontrolled Hypertension: A Prospective Multicenter Observational Study （Chikushi Anti –Hypertension Trial –Ecard(R): CHAT– E Study）

Background：Diuretics cause fewer side effects when administered at low doses and exert synergistic antihypertensive activity in combination with other antihypertensive agents. We investigated the ef ficacy and safety of a combination drug containing candesartan（8 mg） and low dose of hydrochlorothiazide（6.25 mg）（candesartan/HCTZ）in daily medical practice. Methods：A prospective, multicenter, observational study was conducted by 263 medical practitioners using our hospital as the core institution. Patients receiving antihypertensive therapy that included an angiotensin II receptor blocker（ARB） who had not achieved the target clinical blood pressure were switched to candesartan/HCTZ. The primary end– point was the changes of blood pressure and pulse rate. Secondary end– points included adverse events, cardiovascular events, and changes of laboratory test results. Results：One hundred sixteen patients（mean age: 69±11 years; 64 men［55％］） were analyzed and 24 patients dropped out. Major adverse events included hypotension in 4 patients and skin rash in 3 patients. At 6 months, the systolic and diastolic blood pressures were reduced by 20±20 mmHg and 9±12 mmHg（both p＜0.0001）, respectively, while the change of pulse rate was minimal. The target blood pressure was achieved at6 months in 33 patients（35％）. Logistic regression analysis revealed that concomitant diabetes mellitus, chronic kidney disease, dyslipidemia, and a higher baseline diastolic blood pressure were significantly related to not achieving the target blood pressure. Conclusions：In patients with hypertension poorly controlled by ARB– based antihypertensive therapy, candesartan/HCTZ showed a rapid and strong antihypertensive effect that was not influenced by associated cardiovascular risk factors. Candesartan/HCTZ is an effective second – line antihypertensive agent.