Phenylpropanolamine and the risk of hemorrhagic stroke.
BACKGROUND
Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study.


METHODS
Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient.


RESULTS
There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants.


CONCLUSIONS
The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.
Kernan
W N
WN
Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn 06520-8025, USA.
Viscoli
C M
CM
Brass
L M
LM
Broderick
J P
JP
Brott
T
T
Feldmann
E
E
Morgenstern
L B
LB
Wilterdink
J L
JL
Horwitz
R I
RI
D000293:Adolescent; D000328:Adult; D001067:Appetite Depressants / Q000009:adverse effects*; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D003139:Common Cold / Q000188:drug therapy; D003371:Cough / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014663:Nasal Decongestants / Q000009:adverse effects; D010665:Phenylpropanolamine / Q000009:adverse effects*; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000139:chemically induced*
D001067:Appetite Depressants; D014663:Nasal Decongestants; D010665:Phenylpropanolamine