High-risk patients with atrial fibrillation: The importance of protection

In this patient population with a high incidence of co-morbidities in ROCKET AF, the rate of stroke or systemic embolism was 1.7% per year in patients treated with rivaroxaban, compared with 2.2% per year in patients treated with warfarin (p<0.001 for non-inferiority). Rates of non-major clinically relevant bleeding were also comparable with warfarin, with lower rates of intracranial or fatal bleeding events with rivaroxaban treatment. A retrospective analysis showed that rivaroxaban was associated with a favourable net clinical benefit compared with warfarin. When analysed in separate subgroups of patients, the efficacy and safety profile was consistent in patients aged ≥75 years, and in patients with HF, moderate renal impairment, diabetes, and prior stroke or TIA. Subgroup analyses of the ARISTOTLE trial have also demonstrated a consistent benefit–risk profile for apixaban in patients with AF and multiple co-morbidities, history of CAD, HF, prior stroke or TIA and hypertension, with greater absolute benefits in elderly patients. Similarly, history of HF or stroke and higher CHADS₂ scoredid not affect the efficacy and safety profile of dabigatran in RE-LY, and results from ENGAGE AF-TIMI 48 were consistent irrespective of history of HF and stroke or TIA, and greater benefit was demonstrated in elderly patients and in those with a history of CAD. In summary, the NOACs were evaluated in distinct populations with varying degrees of risk. To offer the best protection, consider choosing a NOAC that has been thoroughly tested in high-risk patients, and has been proven to work in patients like yours.

How are high-risk patients with AF managed in real-world clinical practice?

Current guidelines recommend use of a NOAC for the treatment of patients with non-valvular AF and a CHA₂DS₂-VASc score ≥2 (≥3 for female patients), considering individual characteristics and patient preferences. If a patient is ineligible for NOAC treatment, vitamin K antagonists (VKAs) are recommended. Large-scale registries indicate that, in clinical practice, a high proportion of patients with AF are in this high risk category, with ≥85% of patients having a CHA₂DS₂-VASc score ≥2. Treatment of these patients has evolved over time as more options have become available and guidelines have changed, and in 2016, 69% and 87% of patients with a CHA₂DS₂-VASc score ≥2 in the GARFIELD-AF and ORBIT-AF II registries, respectively, were treated with a NOAC. These observations highlight a wide regional variation in treatment of high-risk patients, with substantially more patients receiving NOACs in the US-based ORBIT-AF II registry compared with the worldwide (primary non-US) GARFIELD-AF registry. Variability in the proportion of patients also varies at the country level in GARFIELD-AF and at the state level in ORBIT-AF II. The overall shift from anti-platelet or VKA treatment to NOACs is promising; however, there are still opportunities to improve the implementation of guideline-based recommendations for treatment of high-risk patients with AF.

Summary

The majority of patients with AF have co-morbid conditions that increase their risk of stroke and other CV events. To reduce this risk, is it important that these patients are treated with the appropriate anticoagulation therapy based on their individual patient characteristics and preferences. Phase III trials have shown that NOACs have a consistent benefit–risk profile in patients with AF with co-morbidities. Based on this evidence, current guidelines recommend the use of NOACs in patients with AF and a CHA₂DS₂-VASc score ≥2 (≥3 for female patients), or VKAs if they are ineligible for NOAC therapy. Despite these guidelines, many patients in the real-world are undertreated for their risk of stroke. Overall, the management of complex and vulnerable patients with AF requires expertise to see the bigger picture, and the ability to make informed decisions to improve their outcomes.