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Managing anticoagulation during the COVID-19 pandemic

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Keeping it simple: Single drug approaches to VTE treatment

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Supporting the treatment of patients with low-risk pulmonary embolism at home

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Time for a change? Switching anticoagulants in patients with AF or VTE

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

Patients with AF frequently have co-morbidities

Atrial fibrillation (AF) is associated with many serious co-morbidities, including diabetes chronic kidney disease, heart failure (HF), hypertension and coronary artery disease (CAD).

Patients with these co-morbidities often have an increased risk of stroke compared with patients who only have AF, so it is important that their risk of cardiovascular (CV) events is well managed. However, as every patient with AF is different, expertise to see the bigger picture is required to ensure that patients get the right dose at the right time for the right reason.

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Increased risk of stroke in patients with AF and co-morbidities. The increased risk is shown for selected co-morbidities.

By using scoring tools such as the CHA2DS2-VASc score (incorporating age, sex and history of HF, hypertension, stroke/transient ischaemic attack (TIA)/thromboembolism, vascular disease and diabetes), the overall increase in the risk of stroke in patients with AF and co-morbidities can be calculated. This risk ranges from 0.2–0.3% per year for a patient with AF and no co-morbidities to 12.2–17.4% per year if a patient is aged ≥75 years, female and has all of the co-morbidities included in the score.

 

As patients age, their risk of developing both AF and associated co-morbidities increases, and ageing can also have an effect on the safety of treatments used to manage AF. So what evidence is available to guide treatment options for these complex patients?

For more information on diabetes and renal impairment in patients with AF, please see our newsletters on diabetes renal impairment and co-morbid diabetes and renal impairment.

What did we learn from clinical trials?

Non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) are a common treatment choice for stroke prevention in patients with AF, and have been shown to have a favourable benefit–risk profile in phase III clinical trials in this setting. The ARISTOTLE, RE-LY, ENGAGE AF-TIMI 48 and ROCKET AF studies all included patients ≥75 years of age and with co-morbidities, but the proportion of patients with co-morbidities was highest in ROCKET AF, reflected by a higher mean CHADS2 score.

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Mean CHADS2 score for patients included in phase III NOAC trials in patients with AF

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 recommendedLarge-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.

Treatment of patients with AF undergoing PCI

Among patients with AF and CAD, an estimated 20–25% require coronary revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting surgery. Guidelines recommend triple therapy (oral anticoagulant [NOAC or VKA], clopidogrel and aspirin) for as short as possible before dual therapy (OAC plus clopidogrel or aspirin), or dual therapy immediately in select patients. The 2019 guidelines of the European Society of Cardiology now recommend that a NOAC is used in preference to a VKA in combination with antiplatelet therapy in patients who are eligible for a NOAC. The PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS and ENTRUST-AF PCI trials investigated the efficacy and safety of NOACs in patients with AF undergoing PCI (and/or with a recent acute coronary syndrome in the AUGUSTUS trial). These trials demonstrated that use of a NOAC with a single antiplatelet agent leads to a reduced or similar risk of bleeding whilst maintaining efficacy compared with VKA-based dual or triple therapy.

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Bleeding and efficacy outcome rates with NOAC dual therapy versus VKA-based dual or triple therapy in the PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI trials

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