Editor—Taylor speculates that the reason that the HOPE (heart outcomes prevention evaluation) study did not show a significant relation between blood pressure and outcome was because ramipril was taken at bedtime.1
We believe that this assertion is incorrect for several reasons.
Firstly, the population studied in the paper by Svensson et al differed substantially from the overall HOPE population.2 This substudy focused on 38 patients who had peripheral arterial disease whereas only 43% of the overall HOPE population had such disease. Moreover, the patients recruited from the one centre participating in this substudy had blood pressures that were appreciably different from those in the overall trial (150/79 mm Hg v 139/79 mm Hg).
Secondly, even if a blood pressure reduction were extrapolated from the substudy by Svensson et al (which we believe is not appropriate), the degree of blood pressure reduction may at most be underestimated by 40%. With this taken into account, the blood pressure reduction between ramipril and placebo would be an estimated 4/3 mm Hg, and the effect on myocardial infarction still remains larger than that expected on the basis of epidemiological data.
Thirdly, studies that have assessed two different approaches to blood pressure—for example, the LIFE (losartan intervention for endpoint reduction in hypertension) study examining the effect of angiotensin receptor blockers v β blockers3—show that blockers of the renin-angiotensin-aldosterone system provide greater clinical benefit when blood pressure reduction is identical. Furthermore, other blood pressure lowering agents, such as calcium channel blockers, have been previously studied in populations similar to HOPE with no evidence of clinical benefit.4
Finally, the results of the HOPE study have now been confirmed by other large independent studies.5
Competing interests: Both authors have acted as consultants and have received funding for research from the sponsors of the HOPE study, as well as having attended and presented papers at symposia with support from the sponsoring agencies. The HOPE study was funded by the Medical Research Council of Canada (now Canadian Institutes for Health Research), Hoechst-Marion Roussel (now Aventis), Astra-Zeneca, King Pharmaceuticals, Natural Source Vitamin E Association, Negma, and the Heart and Stroke Foundation of Ontario.
References
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