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CLINICAL STUDY: ANGIOTENSIN ANTAGONISM

Effect of long-term therapy with ramipril in high-risk women

Eva Lonn, MD, MSc, FACC^*,*, Rosa Roccaforte, MD, Qilong Yi, MSc, Gilles Dagenais, MSc, MD, FACC, Peter Sleight, MD, DM, FACC^||, Jackie Bosch, MSc^*, Pamela Suhan, BSN^¶, Mary Micks^*, Jeffrey Probstfield, MD, FACC^#, Victoria Bernstein, MD^**, Salim Yusuf, MBBS, DPhil, FACC^* HOPE Investigators

^* Department of Medicine, Division of Cardiology and Population Health Institute, McMaster University, Hamilton, Ontario, Canada
Fate Benefratelli Hospital, Milan, Italy
Princess Margaret Hospital, Toronto, Ontario, Canada
Quebec Heart Institute, Laval University, Ste-Foy, Quebec, Canada
^|| John Radcliffe Hospital, Oxford University, Oxford, England, United Kingdom
^¶ Cleveland Clinic Foundation, CIeveland, Ohio, USA
^# University of Washington, Seattle, Washington, USA
^** Vancouver Hospital and Health Sciences Centre, Vancouver, British Columbia, Canada

Manuscript received February 12, 2002; revised manuscript received April 19, 2002, accepted May 7, 2002.

^* Reprint requests and correspondence: Dr. Eva Lonn, Hamilton Health Sciences, General Site, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2.
lonnem{at}mcmaster.ca

OBJECTIVES: We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on major cardiovascular (CV) outcomes in high-risk women.

BACKGROUND: The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported.

METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of ramipril in women in the HOPE study. The study randomized 2,480 women aged 55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years.

RESULTS: Treatment with ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of ramipril was similar in women and men.

CONCLUSIONS: Treatment with ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.

Abbreviations and Acronyms   ACE   angiotensin-converting enzyme   AT1   angiotensin II type 1 receptor   CAD   coronary artery disease   CI   confidence interval   CV   cardiovascular   CVD   cardiovascular disease   HOPE   Heart Outcomes Prevention Evaluation trial   LV   left ventricle   MI   myocardial infarction   RR   relative risk

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