Coagulation Dynamics During Coronary Angiography in Patients Receiving Chronic Direct Oral Anticoagulants: Insights from the Randomized POPular MEASURE Study.

BACKGROUND: The role of periprocedural unfractionated heparin (UFH) in patients receiving chronic direct oral anticoagulants (DOACs) undergoing coronary angiography (CAG) remains uncertain. OBJECTIVE: To investigate whether omission of UFH affects thrombin generation and coagulation dynamics. METHODS: In this prospective, randomized, mechanistic study, 120 patients undergoing elective CAG were included: 80 on chronic DOAC therapy randomized to UFH (DOAC + UFH, N=39) or placebo (DOAC + placebo, N=41), and a parallel reference cohort without oral anticoagulation receiving UFH (N=40). Blood samples were collected at baseline, 30, 120, and 240 minutes after UFH administration. Primary endpoint was peak thrombin generation assessed by prothrombin fragment 1+2 (F1+2), with non-inferiority of DOAC + placebo versus reference tested against a prespecified margin of 100 pmol/L. RESULTS: Peak F1+2 levels were lower in DOAC + placebo versus reference (165.5 vs 248.7 pmol/L; mean difference -133.0 pmol/L), with the upper bound of the one-sided 97.5% confidence interval (-36.4 pmol/L) below the non-inferiority margin (p<0.001). No difference was observed between DOAC + placebo and DOAC + UFH (165.5 vs 166.2 pmol/L; p=0.93). Secondary markers were consistent: thrombin generation was lower in DOAC-treated patients versus reference, with no difference in fibrin formation or platelet activation. UFH prolonged clot initiation without affecting clot strength or fibrinolysis. CONCLUSIONS: In patients on chronic DOAC therapy undergoing CAG, omission of periprocedural UFH was not associated with increased thrombin generation. DOAC therapy alone provided sustained suppression of coagulation activation, questioning the routine use of UFH in this setting.