BMJ  2004;329:1403-1404 (11 December), doi:10.1136/bmj.329.7479.1403-d

Letter

The PROGRESS trial three years later

HOPE trial may shed some light

EDITOR—Wennberg and Zimmermann are correct in pointing out that it is simplistic, and potentially misleading, to interpret PROGRESS as indicating that patients with stroke benefit from the combination of perindopril and indapamide.¹ In applying these results clinically, doctors need to know whether the benefit in stroke reduction is due mainly to indapamide or to some synergistic effect of the two. After all, given the prevalence of polypharmacy and the cost, why give two drugs when one might suffice?

To sort out this question it is helpful to compare the results of PROGRESS with those of HOPE, in which ramipril was found to cause a significant relative risk reduction in stroke of 32% (95% confidence interval 16% to 44%) compared with placebo.² This reduction was sustained for fatal and non-fatal strokes and for ischaemic strokes.³

How are clinicians to reconcile the beneficial effect of ramipril monotherapy in HOPE with the non-significant effect of perindopril monotherapy in PROGRESS? The answer may lie in the profile of those enrolled in PROGRESS. Since this was an Australian, New Zealand, and Southeast Asian collaboration, almost 40% of participants in PROGRESS were oriental. The profile of cardiovascular disease among Asians is very different from that among white people.⁴ Ischaemic heart disease predominates in white people, whereas cerebrovascular disease predominates in Asians.

Ethnic variation in blood pressure and response to anti-hypertensive agents has been noted before in other groups—for example, African Americans.⁵ At least part of the disparity between HOPE and PROGRESS may therefore be due to potentially different mechanisms of vascular disease in Asians compared with white people, and perhaps differing response to angiotensin converting enzyme inhibitors.

Rather than being a source of confusion and debate, such conflicting results should prompt new hypotheses, in this case, that potential ethnic variation should be explored. Using the methods of genetic epidemiology in this setting may hold the key to greater understanding of the genetic and environmental factors in vascular disease.

John.Attia{at}newcastle.edu.au, Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW 2300, Australia

Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW 2300, Australia

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Competing interests: None declared.

References

1. Wennberg R, Zimmerman C. The PROGRESS trial three years later: time for a balanced report of effectiveness [with commentary by S MacMahon, B Neal, A Rodgers, J Chalmers]. BMJ 2004;329: 968-71. (23 October.)[Free Full Text]
2. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342: 145-53.[Abstract/Free Full Text]
3. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B, et al. Use of ramipril in preventing stroke: double blind randomised trial. BMJ 2002;324: 1-5.[Abstract/Free Full Text]
4. Menzies Centre for Population Health Research. Profile of cardiovascular diseases, diabetes mellitus and associated risk factors in the western pacific region. Manila: World Health Organization, 1999.
5. Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. N Engl J Med 1993;328: 914-21.[Abstract/Free Full Text]

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