NVAF research roundup

Approximately 90% of people aged 50 years and older in Australia with atrial fibrillation (AF) have non-valvular AF (NVAF). Of these more than half (~57%) are at high risk of stroke, ~30% are at moderate risk and ~13% at low risk.1 Here are some highlights of recent research in stroke prevention in NVAF.

Genetic testing for warfarin sensitivity

Warfarin remains the most widely used anticoagulant despite being associated with serious bleeding complications.2 Genetic testing could identify approximately 40% of patients with NVAF who are at increased risk of over-coagulation and bleeding in the first few months of warfarin therapy, according to a 2015 study. In this study of 14,348 patients with NVAF, 61.7% of warfarin users responded normally, 35.4% were sensitive responders, and 2.9% were highly sensitive to the therapy.2

Compared with normal responders, sensitive and highly sensitive responders were significantly more likely to be overcoagulated during the first 90 days of therapy and to have an increased risk of bleeding (P<0.0001 for both analyses).2
 
Dabigatran vs. warfarin

Pooled analysis from a 2016 observational study comparing clinical and safety findings of dabigatran vs. warfarin, found that although dabigatran 150 mg was not superior in preventing stroke (P=0.066), it had a significantly lower risk of intracranial bleeding (P<0.001).3

Compared with warfarin, dabigatran 150 mg was associated with a significantly greater risk of gastrointestinal (GI) bleeding (P=0.041), potentiated in patients ≥75 years vs. <75 years (P=0.020).3
Rivaroxaban and stroke prevention

XANTUS was the first large-scale observation study investigating the safety and efficacy of a non-Vitamin K antagonist (VKA) anticoagulant in the real-world setting. Average age among the 6784 patients treated with rivaroxaban was 71.5 years and mean treatment duration was 329 days.4
 
The overall number of major bleeding and thromboembolic events and all-cause deaths were low. A total of 11 patients (0.2%) had a haemorrhagic stroke and 32 (0.5%) an ischaemic stroke (see Table). Medication persistence is important in stroke prevention because discontinuation of anticoagulant therapy potentially leaves patients unprotected from stroke risk. In XANTUS, the persistence rate with rivaraboxan at 1 year was 80%. In XANTUS, the incidence of major GI bleeding was lower than seen in a Phase III trial of rivaraboxan (0.9, vs. 2 events/100 patient years, respectively).4

Table. XANTUS: key treatment-emergent thromboembolic/bleeding events.4

  Incidence, n (%) Incidence per 100-pt years (95% CI)
All-cause death 118 (1.7) 1.9 (1.6-2.3)
Thromboembolic events* 108 (1.6) 1.8 (1.5-2.1)
Stroke/SE 51 (0.8) 0.8 (0.6-1.1)
Stroke 43 (0.6) 0.7 (0.5-0.9)
Primary haemorrhagic 11 (0.2)  
Primary ischaemic 32 (0.5)  
SE 8 (0.1) 0.1 (0.1-0.3)
Trans-ischaemic attack 32 (0.5) 0.5 (0.4-0.7)
Myocardial infarction 27 (0.4) 0.4 (0.03-0.6)
Major bleeding 128 (1.9) 2.1 (1.8-2.5)
Intracranial haemorrhage 26 (0.4)
0.4 (0.3-0.6)
*Stroke, systemic embolism, trans-ischaemic attack, myocardial infarction
 
1.Baker IDI Heart & Diabetes Institute. (Accessed March 3, 2016, at www.tinyurl.com/z42d82e).
2. Mega JL, et al. Lancet 2015;385:2280-7.
3. Romanelli RJ, et al. Circ Cardiovasc Qual Outcomes 2016.
4. Camm AJ, et al. Eur Heart J 2015.