eLetters: Evidenced Based Medicine hasn't reached FDA or HPB
In response to: Clinical Update: Phenylpropanolamine and hemorrhagic stroke in women

Lance De Foa
Email: lance_defoa@wawamedicalcentre.com
Affiliation: Wawa Medical Centre
Posted on: May 16, 2001

Editor:

While evidenced based medicine has caught on amongst physicians, it seems that regulatory agencies persist in generating hysteria based blanket recommendations.

PPA has been shown in a case-control study to be associated with increased risk of haemorrhagic stroke primarily in (presumably overwieght), HYPERSTENSIVE, LESS WELL EDUCATED, CIGARETTE SMOKING BLACK FEMALES, primarily when used repeatedly for appetite suppression (odds ratio (OR) of 16.58). That population seems also to be at some risk even at first use of PPA containing cough or cold remedies (OR 3.13). On that basis the FDA and Health Canada issued health advisories and announced they were taking steps to remove PPA from all drug products and requested that all drug companies stop marketing PPA-containing products.

Why? How many million patients find relief from using these medications each year, and what is their level of risk of stroke? The risk is not distributed evenly, since among men there was no increased association of hemorrhagic stroke with use of PPA-containing products. (This suggests to me that PPA may not be a factor in stroke at all. Perhaps those women suffering strokes were also all taking OCPs, which are know to increase stroke risk, particularly in smokers.)

What is the number needed to harm? Consider that since 1969, the use of PPA-containing products has been reported to the US FDA in association with the occurrence of hemorrhagic stroke in only about 60 cases (30+ published case reports and 22 spontaneous reports).1 That is about two reported strokes per year.

This isn't the first time good medicines have been killed because of regulatory over-reaction. The FAA and HPB removed cisapride from the market after fewer than one dozen deaths were observed in people with identifiable risk factors.

These agencies are somewhat inconsistent though - many dozens of men have accepted the well publicized risk of death from use of sildenafil (Viagra) and lost yet it remains on the market.

We place appropriate warning signs on cigarette packages and let smokers continue to place themselves at risk of stroke. Why not do the same with medications? When risk factors for serious harm become known they should be placed in bold type on the package and made well known to health care personel. PPA containing products should probably be placed behind the counter so pharmacists can advise those patients identifiably at increased risk to use other products, not banned from the marketplace.

Reference 1. Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000;343(25):1826-32.

Lance De Foa
P.O. box 1217
Wawa, ON P0S 1K0

I do not hold any securities in any manufacturer of PPA containing products, nor am I aware that any close relative or colleague holds such an interest.

Copyright 2001 Canadian Medical Association or its licensors