What's New in Research: April 8, 2002
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"Effects of angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high risk patients," by Salim Yusuf and 6 others, for the Heart Outcomes Prevention Evaluation Study investigators, New England Journal of Medicine, 342(3):145-53, 20 January 2000.

[Authors' affiliation (project office): Hamilton General Hospital, Ontario, Canada]

Abstract: "Background. Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure. Methods. A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper. Results. A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.0 percent vs. 18.3 percent; relative risk, 0.85; P=0.002), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.63; P=0.03), heart failure (9.0 percent vs. 11.5 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs 7.6 percent; relative risk, 0.84; P=0.03). Conclusions. Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure."

This 2000 report from the New England Journal of Medicine was cited 37 times in current journal articles indexed by ISI during November-December 2001. With its citation total during that two-month span, this was the third-most-cited paper in medicine (excluding reviews) published in the last two years. Prior to the most recent bimonthly count, citations to the paper have accrued as follows:

September-October 2001: 27 citations
July-August 2001: 25
May-June 2001: 45
March-April 2001: 29
January-February 2001: 15
November-December 2000: 26
September-October 2000: 14
July-August 2000: 8
May-June 2000: 8
March-April 2000: 2

Total citations to date: 236

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