Original papers: Therapeutic aspectsThe PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure – a prospective, randomized, controlled prevention trial of the German Hypertension LeagueLüders, Stephanb,e; Schrader, Joachimb; Berger, Jürgenc; Unger, Thomasj; Zidek, Walterk; Böhm, Michaeld; Middeke, Martinf; Motz, Wolfgangg; Lübcke, Corneliab; Gansz, Andreae; Brokamp, Ludmerb; Schmieder, Roland Eh; Trenkwalder, Peteri; Haller, Herrmannl; Dominiak, Petera PHARAO study groupAuthor Information aDepartment of Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany bDepartment of Internal Medicine, St.-Josefs-Hospital, Cloppenburg, Germany cMedical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg-Eppendorf, Germany dDepartment Internal Medicine III–Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Homburg/Saar, Germany eInstitute for Hypertension and Cardiovascular Research, Cloppenburg, Germany fBlood Pressure Institute, Munich, Germany gKarlsburg Cardiovascular Center, Heart and Diabetes Center Mecklenburg-Vorpommern, Germany hDepartment of Nephrology and Hypertension, University Erlangen-Nürnberg, Erlangen-Nürnberg, Germany iMedical Clinic, Klinikum Starnberg, Starnberg, Germany jCenter for Cardiovascular Research (CCR) and Institute of Pharmacology Charité, Universitätsmedizin Berlin, Berlin, Germany kDepartment of Nephrology, Charité Campus Benjamin Franklin, Berlin, Germany lCenter for Internal Medicine, Nephrology, Hannover Medical School (MHH), Hannover, Germany Correspondence to Dr Stephan Lüders, INFO GmbH-Institute for Hypertension and Cardiovascular Research, Krankenhausstr. 13, 49661 Cloppenburg, Germany Tel: +49 4471 16 2951; fax: +49 4471 16 1931; e-mail: [email protected] Journal of Hypertension: July 2008 - Volume 26 - Issue 7 - p 1487-1496 doi: 10.1097/HJH.0b013e3282ff8864 Buy Metrics Abstract Background The prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure study addresses the issue of whether progression to manifest hypertension in patients with high-normal blood pressure can be prevented with treatment. Methods A total of 1008 participants with high-normal office blood pressure were randomized to ramipril treatment group (n = 505) and a control group (n = 503). The patients were followed up for 3 years. Primary endpoint was to prevent or delay the progression to manifest hypertension. Secondary endpoints were reduction in the incidence of cerebrovascular and cardiovascular events, as well as the development of hypertension as defined by ambulatory blood pressure monitoring. Findings One hundred and fifty-five patients (30.7%) in the ramipril group, and 216 (42.9%) in the control group reached the primary endpoint (relative risk reduction 34.4%, P = 0.0001). Ramipril also proved to be more effective in reducing the incidence of manifest office hypertension in patients with baseline ambulatory blood pressure monitoring high-normal blood pressure. The incidence of cerebrovascular and cardiovascular events showed no statistically significant differences between the two groups. Cough was more frequent in the ramipril group (4.8 vs. 0.4%). Interpretation There is now good clinical evidence that patients with high-normal blood pressure (prehypertension) are more likely to progress to manifest hypertension than patients with optimal or normal blood pressure. Additional ambulatory blood pressure monitoring seems to be essential to achieve correct diagnosis. Treatment of patients with high-normal office blood pressure with the angiotensin-converting enzyme inhibitor was well tolerated, and significantly reduced the risk of progression to manifest hypertension. © 2008 Lippincott Williams & Wilkins, Inc.