Refining the treatment of women with unstable angina--a randomized, double-blind, comparative safety and efficacy evaluation of Integrelin versus aspirin in the management of unstable angina.
BACKGROUND
Although women typically develop coronary artery disease several years after men, once they have symptomatic disease their thromboembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unknown. We previously studied platelet functions in siblings from patients with premature coronary artery disease. We observed that platelets from women are responsive than their male counterparts. In particular, platelets from women stimulated ex vivo with various agonists bind more fibrinogen molecules than platelets from men.


OBJECTIVE
We hypothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men.


METHODS
To test this hypothesis, we investigated retrospectively the results of a trial on Integrelin in unstable angina.


RESULTS
We report that platelet aggregation and Holter-detected ischemic episodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggregation and Holter-detected ischemic events are well controlled in men with unstable angina treated with standard therapy including aspirin.


CONCLUSIONS
Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data are consistent with the concept that the platelets from women require stronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery disease.
Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
P J
PJ
Goldschmidt-Clermont
S P
SP
Schulman
P F
PF
Bray
N C
NC
Chandra
D
D
Grigoryev
K R
KR
Dise
M
M
Sagar
R J
RJ
Fox
L D
LD
Coleman
C
C
Richardson
F C
FC
Dorsey
C
C
du Mee
M M
MM
Kitt
P
P
Ouyang
K L
KL
Baughman
G
G
Gerstenblith
D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000188:drug therapy*; D001241:Aspirin / Q000627:therapeutic use*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D008297:Male; D010455:Peptides / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D012449:Safety; D012737:Sex Factors
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077542:Eptifibatide; D001241:Aspirin