Prompt and Sustained Antihypertensive Effectof a Losartan－hydrochlorothiazide Combination Drugin Hypertensive Patients Uncontrolled byAngiotensin Receptor Blockers in the ChikushiAnti－Hypertension Trial－Preminent（CHAT－P）

Objective：Development of combination drugs has been useful to achieve strict bloodpressure（BP）control to reduce cardiovascular events. The aim of the present study was toevaluate the antihypertensive effect and safety of a losartan－hydrochlorothiazide（HCTZ）combination drug.Methods：We are currently conducting a multicenter prospective observational studyin hypertensive outpatients whose BP have not been controlled by angiotensin receptorblocker（ARB）therapy without diuretics.Patients：A total of 672 hypertensive patients receiving ARB therapy at higher thanstandard doses whose BP remained above 140／90 mmHg were enrolled since October2007 and a losartan／HCTZ combination drug was prescribed for each patient.Results：After starting treatment with losartan／HCTZ, BP decreased significantlyfrom 157／87 mmHg（n＝627）to 138／78 mmHg（n＝583）in the 3rd month and 135／77mmHg in the 12th month（n＝507）. The mean pulse rate did not change throughout thestudy period from 73／min at baseline to 73／min in the 12th month. Subgroup analysisshowed that diabetes mellitus（DM）was a significant risk factor for blunting the antihypertensiveeffect of losartan／HCTZ. Laboratory tests revealed that the rates of hyponatremiaand a low eGFR（＜60 mL／min／1.73 m2）were significantly increased by losartan／HCTZtreatment, but this drug had no detrimental effect on uric acid or glucose metabolismduring the 12－month period.Conclusion：The present study conducted by community practitioners demonstrateda potent antihypertensive effect of losartan／HCTZ without major adverse events in hypertensivepatients who had not been controlled by ARB therapy. Concomitant DM was identifiedas a factor that blunted the antihypertensive effect of losartan／HCTZ.