Ticagrelor pharmacokinetics and pharmacodynamics in patients with NSTEMI after a 180-mg loading dose.
The pharmacokinetics after a 180-mg loading dose (LD) of ticagrelor has not been thoroughly investigated in NSTEMI patients. We aimed to compare the ticagrelor uptake and on-treatment platelet reactivity between non-ST-segment elevation myocardial infarction (NSTEMI) patients and a control group of patients with stable coronary artery disease (SCAD) undergoing elective percutaneous coronary intervention. We performed an observational, prospective, single-center study including 40 NSTEMI patients and 20 SCAD controls. Key exclusion criteria included ongoing opioid treatment. Both groups received a 180-mg ticagrelor LD, and blood samples were taken pre-dose and 1, 2, 3, 4, 5, and 6 hours post-LD. Plasma concentrations of ticagrelor and its active metabolite AR-C124910XX were determined by validated methods. Platelet aggregation was tested using ADP-induced multiple electrode aggregometry. The primary endpoint was the time to maximal ticagrelor concentration (Tmax). Clinical trial registration identifier number: NCT02292277. None of the pharmacokinetic variables differed significantly between the groups, including the Tmaxof ticagrelor (2.0h [1.0-3.0] versus 2.0h [2.0-3.0], p = 0.393) and the active metabolite AR-C124910XX (3.0 [2.0-4.0] versus 3.0 [2.5-4.0], p = 0.289). High on-treatment platelet reactivity (HPR) was defined as > 46 aggregation units and was at one hour seen in 15% of the NSTEMI patients versus 10% of the controls (p = 1.0). At two hours post the 180-mg ticagrelor LD, 3% of the NSTEMI patients had HPR compared with none of the controls (p = 1.0). In conclusion, the uptake of ticagrelor was not significantly slower in NSTEMI patients not receiving opioids compared with the SCAD controls, leading to adequate onset of platelet inhibition in both groups.
a Department of Cardiothoracic Surgery and Anesthesiology , Karolinska University Hospital, Stockholm, Sweden.|b Department of Molecular Medicine and Surgery , Karolinska Institutet, Stockholm, Sweden.
Manne
M
Holm
c Department of Science and Education, Södersjukhuset (Stockholm South General Hospital) , Karolinska Institutet , Stockholm , Sweden.
Per
P
Tornvall
a Department of Cardiothoracic Surgery and Anesthesiology , Karolinska University Hospital, Stockholm, Sweden.
Julia
J
Westerberg
a Department of Cardiothoracic Surgery and Anesthesiology , Karolinska University Hospital, Stockholm, Sweden.
Shaym
S
Rihan Hye
a Department of Cardiothoracic Surgery and Anesthesiology , Karolinska University Hospital, Stockholm, Sweden.|b Department of Molecular Medicine and Surgery , Karolinska Institutet, Stockholm, Sweden.
Jan
J
van der Linden
D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001711:Biotransformation; D001792:Blood Platelets / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072658:Non-ST Elevated Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D013548:Sweden; D000077486:Ticagrelor
C561701:AR C124910XX; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000244:Adenosine Diphosphate; D000077486:Ticagrelor; D000241:Adenosine
Myocardial Infarction; pharmacokinetics; platelet inhibitor