Investigating the mechanisms of hyporesponse to antiplatelet approaches.
Hyporesponsiveness, or resistance, to antiplatelet therapy may be a major contributor to poorer outcomes among cardiac patients and may be attributed to an array of mechanisms--both modifiable and unmodifiable. Recent evidence has uncovered clinical, cellular, and genetic factors associated with hyporesponsiveness. Patients with severe acute coronary syndromes (ACS), type 2 diabetes, and increased body mass index appear to be the most at risk for hyporesponsiveness. Addressing modifiable mechanisms may offset hyporesponsiveness, while recognizing unmodifiable mechanisms, such as genetic polymorphisms and diseases that affect response to antiplatelet therapy, may help identify patients who are more likely to be hyporesponsive. Hyporesponsive patients might benefit from different dosing strategies or additional antiplatelet therapies. Trials correlating platelet function test results to clinical outcomes are required. Results from these studies could cause a paradigm shift toward individualized antiplatelet therapy, improving predictability of platelet inhibition, and diminishing the likelihood for hyporesponsiveness.
Braunwald
Eugene
E
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, 350 Longwood Avenue, Boston, Massachusetts 02115, USA. ebraunwald@partners.org
Angiolillo
Dominick
D
Bates
Eric
E
Berger
Peter B
PB
Bhatt
Deepak
D
Cannon
Christopher P
CP
Furman
Mark I
MI
Gurbel
Paul
P
Michelson
Alan D
AD
Peterson
Eric
E
Wiviott
Stephen
S
D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D020022:Genetic Predisposition to Disease; D006801:Humans; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin