Stroke and aspirin non-responder patients: relation with hypertension and platelet response to adenosine diphosphate.
Despite its widespread use, there are many concerns about the efficacy of aspirin in the secondary prevention of cardiovascular events after stroke, leading to the concept of aspirin non-response (ANR). Although the mechanisms of ANR remain uncertain, it is expected to be due to a combination of clinical, biological and genetic characteristics affecting platelet function. In this study, we investigated whether clinical and/or biological factors such as hypertension and platelet response to ADP could contribute to the ANR. As a secondary objective, we determine whether ANR and collagen/ADP closure time (CADP-CT) could be related to platelet glycoprotein single nucleotide polymorphisms (SNPs). One hundred patients on aspirin (160 mg/day) were enrolled. ANR was measured with a platelet function analyzer (PFA-100); genotyping of four SNPs (GP IIIa, GP Ia, P2Y12 and GP VI) was performed using a tetra-primer amplification refractory mutation system. Using a collagen/epinephrine-coated cartridge on the PFA-100, the prevalence of ANR was 15% (n = 15). In the ANR group, (i) CADP-CT was significantly shorter and (ii) hypertension was an independent clinical predictive factor of ANR (OR = 4.25; 95%CI: 1.06-17.11). No clear relation was found between CADT-CT and platelet gene polymorphism as well as ANR status and SNPs. In conclusion our study confirms the independent relationship between hypertension, platelet hypersensitivity to ADP and aspirin (160 mg/day) non-response. The differential sensitivity to aspirin may have potential clinical implications, where adaptation of antiplatelet therapy is necessary according to a patient's clinical and genetic characteristics.
Département de Neurologie, CHU Poitiers, Poitiers Cedex, France.
G
G
Godeneche
N
N
Sorel
S
S
Ragot
J C
JC
Chomel
J P
JP
Neau
L
L
Macchi
D000244:Adenosine Diphosphate / Q000627:therapeutic use*; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D001241:Aspirin