Secondary or malignant hypertension |
Inter-arm BP difference: SBP > 20 mmHg or DBP > 10 mmHg |
Symptomatic orthostatic hypotension |
Cardiovascular history |
MI, congestive heart failure (NYHA class III or IV), CABG, PTCA, or angina < 3 months before enrollment |
Severe cerebrovascular disease (stroke, cerebral infarction, or cerebral hemorrhage) |
Arrhythmia (significant ventricular tachycardia, atrial fibrillation, or atrial flutter) |
Significant valvular disease: aortic stenosis or mitral stenosis |
Hypertrophic cardiomyopathy |
Type 1 DM or HbA1c > 9% at screening |
Significant renal or hepatic disease |
Dialysis, cirrhosis, biliary tract obstruction, cholestasis, or liver failure |
eGFR (MDRD) < 30 mL/min/1.73 m2, hyperkalemia (>5.5 mmol/L) or hypokalemia (<3.5 mmol/L) |
AST or ALT > 3 times the upper limit of normal |
Any chronic inflammatory disease requiring chronic anti-inflammatory treatment (including rheumatoid arthritis, systemic lupus erythematosus, or connective tissue disease) |
Moderate or malignant retinopathy < 6 months before enrollment (e.g. moderate or severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy) |
Surgical or medical disease that may affect drug absorption, distribution, metabolism, or excretion |
Cancer history with current treatment or treatment within five years |
Pregnancy, childbearing potential without adequate contraception, or breast-feeding |
Previous hypersensitivity reaction to renin-angiotensin system inhibitors |
Alcohol or drug abuse within the previous two years |
Poor compliance during placebo run-in period: < 70% |