Effect of sinus rhythm restoration on markers of thrombin generation in atrial fibrillation

Atrial fibrillation (AF) confers a hypercoagulable state; however, it is not clear whether restoration of sinus rhythm is associated with normalisation of markers of thrombogenesis. We studied the impact of sustained sinus rhythm on prothrombotic markers, and their predictive abilities in foreseeing rhythm outcome after cardioversion. In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion of persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion. Endogenous thrombin potential (ETP), prothrombin fragment 1 + 2 (F1 + 2) and D-dimer were measured before cardioversion and at end of study. These markers were also measured in a reference group comprising 49 subjects without AF. The markers remained unchanged in those 28 patients who maintained sinus rhythm. Discontinuation of warfarin treatment in a subset of 13 low-risk patients in sinus rhythm was associated with significantly higher levels of D-dimer and F1 + 2 compared to the reference group; D-dimer (456 ng/mL (276, 763) vs. 279 ng/mL (192, 348), p = 0.002) and F1 + 2 (700 pmol/L (345, 845) vs. 232 pmol/L (190, 281), p < 0.001). None of the markers were associated with rhythm outcome after electrical cardioversion. Sustained sinus rhythm for 6 months after cardioversion for AF had no impact on ETP, F1 + 2 or D-dimer levels. Discontinuation of warfarin in low-risk patients with sustained sinus rhythm was associated with significantly higher levels of D-dimer and F1 + 2 compared to the reference group. Our results suggest persistent hypercoagulability in AF patients despite long-term maintenance of sinus rhythm. The CAPRAF study was registered at clinicaltrials.gov (NCT00130975) in August 2005.