Differential effects of dual antiplatelet and dual antithrombotic therapy on hemostasis in chronic coronary syndrome patients: the DEFINE CCS study

Optimal long term antithrombotic treatment in high-risk chronic coronary syndrome (CCS) patients remains uncertain. Both ticagrelor (60 mg BID) and low-dose rivaroxaban (2.5 mg BID) in addition to low-dose aspirin resulted in significant reductions in major cardiovascular events in high-risk patients at the expense of increased bleeding risk. We aimed to compare the effects of both strategies on bleeding time, fibrin clot lysis time and inflammatory biomarkers in CCS patients with history of acute coronary syndrome. Twenty aspirin-treated patients were recruited into a randomized crossover study to receive ticagrelor 60 mg BID in 1 week and rivaroxaban 2.5 mg BID in the other with a 2-week washout period in between. Outcome measures were determined at the start and end of each treatment week. Two-way ANOVA was used to determine difference in treatment effect. Data are presented as mean ± SD. At baseline, there was no significant difference in any studied outcome measure. Bleeding time was significantly longer with ticagrelor compared to rivaroxaban (Ticagrelor: 897 ± 481secs vs. Rivaroxaban: 440 ± 184 secs; p = .0001). Fibrin clot lysis time was not impacted by ticagrelor but significantly dropped post treatment with rivaroxaban (Ticagrelor: 5743 ± 2590 secs vs. Rivaroxaban: 4309 ± 2308 secs; p = .0049). Neither treatment had an impact on levels of high-sensitivity CRP or white cell count. In conclusion, ticagrelor 60 mg BID has greater impact on bleeding time compared to rivaroxaban 2.5 mg BID. Whereas rivaroxaban, positively modulates fibrin clots, rendering them more prone to lysis. Patients with history of having heart attacks remain at risk of further major cardiovascular events. To mitigate this risk, blood thinners are required. Typically, long term aspirin is recommended for the majority of patients beyond the first year after suffering a heart attack. In patients who are deemed to be high risk, additional blood thinners may be required. Two therapies have been shown to improve outcomes, ticagrelor and rivaroxaban. It is not known, which is more effective or safest in terms of bleeding risk. We assessed the effects of both treatments on markers of bleeding tendency and thrombosis risk. Twenty patients were recruited into this study to receive 1 week of treatment with ticagrelor and another week of rivaroxaban with 2 weeks in-between. We studied the time it takes for bleeding to stop after puncturing the forearm with a lancet and the time it takes for clots formed in plasma samples to lyse. For the first time, we showed ticagrelor to result in greater increase in bleeding time compared to rivaroxaban, whereas rivaroxaban resulted in clots that are easier to dissolve. Larger trials will be needed to assess whether these effects translate into differences in clinical outcomes.