Oral anticoagulants as stroke prevention in the setting of atrial fibrillation and cancer

Abstract: Background Cancer patients have elevated risk of both stroke and bleeding in comparison to individuals without cancer. The general population is ageing and the group of patients with atrial fibrillation (AF) and cancer concomitantly becomes larger; however, there is lack of stroke prevention guidelines addressing these patients. The aim of this thesis was to describe stroke prevention with oral anticoagulants (OACs) in AF patients with cancer and to estimate net benefit. Methods and Results Register data on all patients with at least one registered diagnosis of AF in the Swedish Patient Register between 1 July 2005 and 31 December 2017 were cross-matched with the Drug Register, the Cancer Register, the Cause of Death Register, and the Riksstroke Register. Patients with a new cancer diagnosis within the past year and patients without a cancer diagnosis in the last five years were included. Study I: Propensity score matching for the likelihood of being on OAC treatment after having been diagnosed with AF was used to study patients with and without OAC treatment. Cancer (n=14,472) and non-cancer (n=304,286) patients were analysed separately. Amongst cancer patients, there was an overall net benefit of OAC use for the composite outcome of ischaemic stroke, extracranial arterial thromboembolism, bleedings, and death (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.78–0.85). This result is driven by patients with at least intermediately increased stroke risk. Limiting follow-up to one year and accounting for the competing risk of death, there was a net cerebrovascular benefit for OACs generally (subhazard ratio [sHR]: 0.67, CI: 0.55–0.83) and for non-vitamin K antagonist OACs (NOACs) (sHR: 0.65, CI: 0.48–0.88) over warfarin. Study II: In Riksstroke we identified all AF patients who had suffered an ischaemic stroke. Amongst cancer patients (n=1,518) the proportion prescribed OACs at discharge increased by 40.2% after NOACs were introduced, compared with 69.3% in non-cancer patients (n=50,953), even though stroke and bleeding risk scores remained similar between the patient groups. OAC dispensation during the following year increased less in cancer patients (43.8% to 64.5%) than in non-cancer patients (46.0% to 74.9%), and the median time to OAC dispensation was significantly longer (94 vs. 30 days) after the introduction of NOACs. Study III: There was no difference in net cerebrovascular benefit amongst patients with cancer (n=8,228) and without cancer (n=323,394) during the year following OAC initiation adjacent to AF diagnosis accounting for the competing risk of death (sHR: 1.12, CI: 0.98– 1.29). Cancer patients had a higher risk of non-fatal bleedings (sHR: 1.69, CI: 1.56–1.82). NOACs were associated with lower risk of both cerebrovascular events and bleedings compared to warfarin. Amongst NOAC treated, cancer was not a predictor of intracranial bleedings. Conclusions AF patients with cancer have a net benefit from OAC treatment and may be treated according to current AF guidelines for the general AF population, but they should be monitored closely for bleedings. NOACs appear safer than warfarin, but seem underutilised as secondary prevention after ischaemic stroke amongst cancer patients.