Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications.
OBJECTIVE
To correlate inhibition of platelet aggregation (IPA) with bleeding events assessed by TIMI, GUSTO, and BleedScore scales in a large cohort of patients with coronary artery disease (CAD) and ischaemic stroke (IS) treated with chronic low-dose aspirin plus clopidogrel. Data from recent trials and registries suggest a link between increased risk of bleeding and cardiovascular mortality. However, the potential association of bleeding risk and IPA is not established. It may play a critical role for the safety of more aggressive platelet inhibition or/and individual tailoring of antiplatelet strategies.


RESULTS
Secondary post hoc analyses of 5 microM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore scales in a combined data set consisting of patients with documented CAD (n = 246) and previous IS (n = 117). Demographic characteristics differ substantially depending on the underlying vascular disease; however, IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious haemorrhagic events, where the TIMI scale was the most exclusive, whereas BleedScore was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during two to three distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. Inhibition of platelet aggregation >50% strongly correlates with minor (r(2) = 0.58, P < 0.001; c-statistic = 0.92), but not severe (r(2) = 0.11, P = 0.038; c-statistic = 0.57), bleeding events.


CONCLUSIONS
Chronic oral combination antiplatelet regimens are associated with a very high (56.5-60.7%) prevalence of superficial bleeding episodes, which are grossly underestimated in trials and registries. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. Although IPA is well suited for defining the risk of minor complications, prediction of more severe bleeding events may be challenging.
HeartDrug Research Laboratories, Johns Hopkins University Towson, 7600 Osler Drive, Towson, MD 21204, USA. heartdrug@aol.com
Victor
V
Serebruany
Sunil V
SV
Rao
Matthew A
MA
Silva
Jennifer L
JL
Donovan
Abir O
AO
Kannan
Leonid
L
Makarov
Shinya
S
Goto
Dan
D
Atar
D000368:Aged; D001780:Blood Coagulation Tests / Q000379:methods; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000145:classification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine