By Michael H. Crawford, MD, Editor

SYNOPSIS: An observational study of patients with mechanical heart valves on oral anticoagulants who had an intracranial hemorrhage demonstrates that it generally is safe to resume anticoagulants after 14 days. However, in high-risk-for-thromboembolism patients, such as those with atrial fibrillation, restarting anticoagulants six to 13 days postoperative may be considered.

SOURCES: Kuramatsu JB, Sembill JA, Gerner ST, et al. Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves. Eur Heart J 2018;39:1709-1723.

Verheugt FWA. Anticoagulation resumption after intracranial haemorrhage with mechanical valves: A data-free zone. Eur Heart J 2018;39:1724-1725.

The optimal time to resume oral anticoagulation (OAC) in patients with mechanical heart valves who have suffered an intracerebral hemorrhage (ICH) is controversial. Kuramatsu et al performed a nationwide observational cohort study of patients on OAC who suffered an ICH and identified 137 patients with mechanical heart valves out of 2,504 collected between 2006 and 2015 from 22 centers (RETRACE I and II studies). Only those with an initial international normalized ratio (INR) > 1.5 who survived at least 72 hours were included. Patients were divided into two groups: no therapeutic anticoagulation (TA) during the hospitalization or only venous thromboembolism (TE) prophylaxis (n = 71) and TA (n = 66). The primary safety outcome was major hemorrhage (expanding ICH or extracranial) during hospitalization. Secondary outcomes included thromboemboli, 90-day mortality, functional status, and when TA resumed.

Optimal INR reversal (< 1.3 within four hours) was achieved in 25% of patients, but this was not associated with subsequent TE. Hemorrhagic complications were noted in 15% of patients and were higher in those restarted on TA after 72 hours (26%) vs. those not (5.6%; P = 0.001). There was a trend toward lower TE in those restarted on TA (1.5% vs. 9.9%; P = 0.06). A propensity score matching analysis showed that restarting TA increased the incidence rate of hemorrhagic complications (likelihood ratio, 8.0; 95% confidence interval, 2.73-28.54; P < 0.01). TA patients demonstrated an increased risk of hemorrhage until day 13 post-ICH and an increased risk of hemorrhage plus TE until day six. TA was not associated with mortality or functional outcome at discharge or at 90 days post-ICH. Patients with concomitant atrial fibrillation (AF) exhibited an increased rate of hemorrhagic and TE complications (34% vs. 16%; P = 0.02). AF patients restarted on TA did not show increased hemorrhage, but those not started on TA demonstrated higher rates of TE, which increased their combined endpoint (33% vs. 8%; P = 0.01). The authors concluded that optimal timing of the resumption of TA after ICH was 14 days, but the earliest starting point was six days in those at high risk of TE, such as those with concomitant AF.

COMMENTARY

This is the largest study so far of this issue, for which a randomized trial would be unethical. Although rare (0.5% per year), ICH is a serious complication of OAC therapy for mechanical heart valves and a complication that often proves fatal. Currently, mechanical heart valves must be anticoagulated by vitamin K antagonists and rapid reversal of their effects is difficult to achieve. Even in this study, which almost exclusively used prothrombin complex concentrates, complete reversal within four hours was achieved in only 25% of patients. Despite this, ICH expansion was reduced significantly through reversal of anticoagulation without an increase in TE. A unique feature of the study was a 72-hour hold before anticoagulants could be administered to prevent confusing disease outcomes with treatment effects. The main thrust of the study: When could anticoagulants be restarted safely?

Kuramatsu et al demonstrated that complete safety from major hemorrhage did not start until > 13 days after ICH. But with every day off anticoagulants, the risk of TE rose such that after six days, the risk of the combined endpoint of hemorrhage or TE was higher. Thus, the authors concluded that in those at high risk of TE, anticoagulation could be considered at six days. Such patients would include those with AF, with a prosthetic mitral valve, or with a caged-ball valve prosthesis. Interestingly, other studies of AF alone have shown that the optimal time for restarting anticoagulants is seven or eight weeks following ICH. The major limitation of the study, besides its retrospective and observational nature, is that there was no common protocol between the 22 centers. Further, each patient was treated according to the practice of the physicians taking care of him or her. Still, we are not likely to obtain better information than the data collected in this careful analysis. This study can inform our decision-making, but probably won’t change the current guidelines (European Society of Cardiology 2017, which state that heparin can be started on day three and vitamin K antagonists at day seven after ICH).1 The Kuramatsu et al study suggests this may be too aggressive.

REFERENCE

  1. Halvorsen S, Storey RF, Rocca B, et al; ESC Working Group on Thrombosis. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: Expert consensus paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J 2017;38:1455-1462.