TY - JOUR
T1 - Vorapaxar and diplopia
T2 - Possible off-target PAR-receptor mismodulation
AU - Serebruany, Victor L.
AU - Fortmann, Seth D.
AU - Rao, Sunil V.
AU - Tanguay, Jean Francois
AU - Lordkipanidze, Marie
AU - Hanley, Daniel F
AU - Can, Mehmet
AU - Kim, Moo Hyun
AU - Marciniak, Thomas A.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, has been evaluated in the successful TRA2P trial and the failed TRACER trial. The drug is currently approved for post myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The FDA ruled that the vorapaxar safety profile is acceptable. However, both trials revealed excess diplopia (double vision) usually reversible after vorapaxar. The diplopia risk appears to be small (about 1 extra case per 1,000 treated subjects), but real. Overall, there were 10 placebo and 34 vorapaxar diplopia cases (p=0.018) consistent for TRACER (2 vs 13 cases; p=0.010) and for TRA2P (8 vs 21 cases; p=0.018). Hence, we review the FDA-confirmed evidence and discuss potential causes and implications of such a surprising adverse association, which may be related to off-target PAR receptor mismodulation in the eye.
AB - Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, has been evaluated in the successful TRA2P trial and the failed TRACER trial. The drug is currently approved for post myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The FDA ruled that the vorapaxar safety profile is acceptable. However, both trials revealed excess diplopia (double vision) usually reversible after vorapaxar. The diplopia risk appears to be small (about 1 extra case per 1,000 treated subjects), but real. Overall, there were 10 placebo and 34 vorapaxar diplopia cases (p=0.018) consistent for TRACER (2 vs 13 cases; p=0.010) and for TRA2P (8 vs 21 cases; p=0.018). Hence, we review the FDA-confirmed evidence and discuss potential causes and implications of such a surprising adverse association, which may be related to off-target PAR receptor mismodulation in the eye.
KW - Adverse events
KW - Clinical trials
KW - Diplopia
KW - PAR receptor
KW - Safety
KW - Vorapaxar
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U2 - 10.1160/TH15-11-0882
DO - 10.1160/TH15-11-0882
M3 - Article
C2 - 26887783
AN - SCOPUS:84964835087
SN - 0340-6245
VL - 115
SP - 905
EP - 910
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 5
ER -