Top Ten Things Every Clinician Should Know About the 2018 Antithrombotic Therapy Atrial Fibrillation Guidelines

The American College of Chest Physicians (ACCP) recently updated their guideline recommendations for the use of antithrombotics for the prevention of stroke in patients with atrial fibrillation (aka the Chest Guidelines). Here’s what’s new, who shouldn’t receive treatment based on the CHA₂DS₂-VASc score, and why the guideline panel recommends calculating a patient’s SAME-TTR score.  Be sure to listen to the podcast for additional insights!

1. The CHA₂DS₂-VASc Score makes its CHEST debut. When stratifying risk for stroke and thromboembolism in the setting of atrial fibrillation (AF) the focus is to identify “low risk” patients (i.e. those that don’t require anticoagulation). Currently available data suggests that the CHA₂DS₂-VASc score is better than other risk scoring systems at identifying low-risk patients. To be considered low risk as a male you would need to have a CHA₂DS₂-VASc score of 0. Females are considered low risk if they have a CHA₂DS₂-VASc score of 1 since there is no difference in stroke risk based on sex until age 65. Male patients who score > 1 and females who score > 2 should be offered stroke prevention. This differs from the AHA/ACC/HRS guidance as they do not have sex-specific recommendations and stroke prevention is considered “optional” for patients with a CHA₂DS₂-VASc score of 1.

CHA₂DS₂-VASc Scoring System

2. Vitamin K antagonists are no longer a preferred option. In patients who are eligible for oral anticoagulation (OAC), the non-VKA oral anticoagulants (also referred to as direct oral anticoagulants, or DOACs) are now preferred over a vitamin K antagonist (VKA – most commonly warfarin in North America) for AF-related stroke prevention. This shift is driven predominantly by pooled evidence suggesting that DOACs are better at preventing stroke and embolic events than VKAs — however this is driven by decreases in hemorrhagic stroke (rates of ischemic stroke appear similar for DOACs vs VKAs). Data also suggests that DOAC use results in a lower risk of major bleeding as well as all-cause mortality compared to VKAs — however gastrointestinal bleeding is significantly increased. Additional benefits of DOACs compared to VKAs include rapid onset and offset, fewer drug interactions, more predictable anticoagulation effects which allow for fixed dosing with no routine monitoring, and lack of interactions with dietary vitamin K.

^{*Lower doses of edoxaban not indicated for stroke prevention}

3. The more things change, the more they should stay in the SAME-TTR. Although the 2018 guidelines favor the use of DOACs over VKAs in most situations, there are still patients for whom VKAs are both a reasonable and (perhaps even) preferred treatment option. Studies have shown that numerous factors contribute to a patient’s time in therapeutic range (TTR) while taking VKAs, including both patient-related and healthcare system-related factors. A new scoring system was developed to predict how likely a patient is to achieve a TTR of ≥65% while on VKAs. A score ≥2 suggest a patient has a lower likelihood of maintaining the INR in the target INR range.  Patients who are unable to maintain the INR in the target range would require more frequent INR checks, more frequent follow-up, and/or counseling. This scoring system has also been evaluated in numerous clinical trials, including patients who have been treated for venous thromboembolism (VTE), so it may hold similar predictive value in this patient population as well.

SAME-TT₂R₂ VKA Scoring System

4. In the absence of atherosclerotic disease, antiplatelet agents are no more. Given conflicting data regarding their benefit as well as limitations in study designs and the higher bleeding risk, mono- and dual-antiplatelet therapy are no longer recommended for stroke prevention in the setting of atrial fibrillation regardless of CHA₂DS₂-VASc score. It is important to note that this recommendation excludes patients with a compelling indication for antiplatelet therapy (e.g. acute coronary syndrome, stents). Patients with atherosclerotic disease and a CHA₂DS₂-VASc score that indicates anticoagulation is needed for stroke prevention should receive both an anticoagulant and antiplatelet agent(see item #5 below).

5. Balancing thrombotic and bleeding risk in patients with atrial fibrillation and coronary artery disease: The authors give weak recommendations on managing the need for both anticoagulation and antiplatelet therapy in the setting of coronary artery disease (see table below). The risk of bleeding, stroke, stent thrombosis, and recurrent cardiac ischemia should all be considered. DOACs are not preferred over VKAs in the setting of coronary artery disease due to limited data but overall bleeding risk appears to be lower with a DOAC. Clopidogrel is preferred over other P2Y12 inhibitors because the combination of ticagrelor and prasugrel with VKAs or DOACs are not well studied and observational data suggests there is a higher bleeding risk with these agents. The duration of concomitant antiplatelet-anticoagulant therapy should be based on the HAS-BLED score and the presence of acute coronary syndrome (ACS). In general, antiplatelet therapy should not be continued for more than 12 months post-PCI.

Recommendations in the Setting of Atrial Fibrillation and Coronary Artery Disease

^{OAC: oral anticoagulation, DAPT: dual antiplatelet therapy, SAPT: single antiplatelet therapy}

^{*Clopidogrel is preferred}

6. Some DOACs are preferred over other DOACs in patients following ACS or percutaneous coronary intervention (PCI). To date, the only DOACs with evidence supporting their use post-ACS or PCI are dabigatran 150 mg and 110 mg (NOTE – the 110mg dose is not FDA approved for stroke prevention) as well as rivaroxaban 15 mg. Studies have shown that DOACs in combination with aspirin are not as risky in terms of major bleeding when compared to VKAs in combination with aspirin. Thankfully, the HAS-BLED scoring system is predictive of bleeding risk in the setting of ACS/PCI-stenting.

7. Recommendations for women of child-bearing age are unchanged. The authors recommend against the use of DOACs in patients who are breast-feeding, attempting to get pregnant, or become pregnant. VKAs, low molecular weight heparin, and unfractionated heparin are still thought to be safe in lactating women. The guideline panel’s stance on continuing VKAs with frequent pregnancy tests over proactively switching to low molecular weight heparin in women who are trying to conceive has not changed. Given the unknowns with the DOACs, the guideline authors suggest switching to a VKA before attempting pregnancy.

8. DOAC reversal agents, FINALLY!  Some clinicians have been less inclined to prescribe DOACs due to the lack of specific reversal agents even though the majority of bleeds occurring in patients taking DOACs can be managed with medication discontinuation and supportive care alone. Patients and clinicians may be more at ease now that Praxbind and Andexxa are available. However, it’s important to note that these reversal agents are very costly, some hospitals don’t stock them, and they should be reserved for life-threatening bleeds.

9. Anticoagulation in patients with CKD. All available DOACs rely (in varying degrees) on renal elimination and this must be taken into account when selecting an oral anticoagulant. AF patients with chronic kidney disease (CKD) are more likely to experience an ischemic stroke compared to AF patients without CKD, but current stroke risk scoring systems don’t include CKD in their risk assessment but it’s a potentially discriminating factor. Conversely, CKD also increases a patient’s risk of major and intracranial bleeding, making anticoagulation in this population a tough balancing act. The guideline authors recommend that both male and female AF patients with a GFR 30-59 mL/min and a CHA₂DS₂-VASc score of at least 2 should receive anticoagulation therapy. A VKA or a renal dose-adjusted DOAC are both acceptable options.

10. What’s the deal with dabigatran 110 mg? The mid-level dose of dabigatran is now a suggested alternative oral anticoagulant (along with apixaban and edoxaban) for AF patients with a history of unprovoked bleeding or warfarin-associated bleeding, or who are otherwise at high-risk of bleeding. This recommendation is based on data demonstrating a lower risk of major bleeding with these agents compared to VKAs.  It should be noted that the 110 mg dose of dabigatran is currently only FDA approved for reducing the risk of DVT/PE following hip replacement surgery. The 110 mg dose received FDA approval in 2015, a full 5 years after the FDA approved the 75 mg and 150 mg doses of dabigatran for stroke in prevention. The decision to approve dabigatran 75 mg rather than the 110 mg dose (which was used in the RE-LY study) was a controversial one as the 75 mg dose had not been studied in humans. The 110mg dose is a more evidence-based choice.