Background: Evidence is lacking regarding anticoagulation management in patients with mechanical heart valves(MHV) after intracerebral hemorrhage(ICH). Aim of the study was to investigate incidence rates of hemorrhagic and thromboembolic complications according to anticoagulation strategies and to define an optimal time-window to restart therapeutic anticoagulation(TA).
Methods: Pooled individual-data(n=2504) from the German-wide multicenter study (RETRACE-program) were used to identify patients with MHV(n=166) and ICH under oral anticoagulation(OAC). The primary outcome comprised frequencies and incidence rates of new hemorrhagic complications according to treatment (restarted TA vs. no TA). Secondary outcomes consisted of thromboembolic complications, composite outcome (hemorrhagic & thromboembolic), timing of restarted anticoagulation. Incidence rates were compared by conditional maximum likelihood(CML)estimates. Adjusted analyses included ps-matching and multivariable Cox-regressions to identify an optimal timing of TA.
Findings: Overall, 137 MHV-patients were eligible for outcome analyses and 66 restarted TA compared to 71 without TA during hospital stay. Patients on TA showed a significantly increased rate of hemorrhagic complications (TA=17/66(25·8%) versus no-TA=4/71(5·6%);p<0·01). Controlling for treatment crossover by analyzing actual days on treatment provided a significant CML-incidence rate-ratio of 10·31([95%CI:3·67-35·70];p<0·01) in disadvantage of TA. Adjusted analyses of TA-timing provided significant harm until day 14 after ICH(HR=7·06,[95%CI:2·33-21·37];p<0·01). Balancing both complications(hemorrhagic and thromboembolic) showed that TA was significantly associated with an increased rate for this composite outcome until day 6 after ICH(HR=2·51,[95%CI:1·10-5·70];p=0·03).
Interpretation: In patients with MHV and anticoagulation-associated ICH restarted TA was related to increased hemorrhagic complications until two weeks after ICH. Optimal weighing - between least risks for thromboembolic and hemorrhagic complications - provided an earliest starting point of TA at day 6 which should be reserved for patients at high thromboembolic risk.