EDITORIAL Recent Changes in Practice Guidelines for Atrial Fibrillation Management Lisa Charneski,* and James M. Hollands Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy at University of the Sciences, Philadelphia, Pennsylvania
KEY WORDS atrial fibrillation, arrhythmia, guidelines, anticoagulation, stroke. (Pharmacotherapy 2014;**(**):**–**) doi: 10.1002/phar.1498
Updated treatment guidelines for the management of patients with atrial fibrillation were recently released by the American College of Cardiology/American Heart Association Task Force.1 Although ventricular rate control and anticoagulation still remain the cornerstone of treatment for most patients, several changes set forth in these guidelines will likely have a major impact on the care of patients with atrial fibrillation. Switching from the CHADS2 scoring system (1 point each for congestive heart failure, hypertension, age 75 years or older, or diabetes mellitus, and 2 points for previous stroke or transient ischemic attack [TIA]) to CHA2DS2VASc (1 point each for congestive heart failure, hypertension, diabetes mellitus, vascular disease, age 65–74 years, or female sex, and 2 points each for age 75 years or older or previous stroke or TIA) for risk stratification and the emergence of the newer oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban contribute to most of the changes in the new guidelines, whereas optimal heart rate targets remain controversial.1, 2 The opinions expressed in this editorial are those of the author and do not necessarily represent the position of Pharmacotherapy or the American College of Clinical Pharmacy. Invited editorials are not peer reviewed. *Address for correspondence: Lisa Charneski, Associate Professor of Clinical Pharmacy, Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy at University of the Sciences, 600 S. 43rd Street, Box 34, Philadelphia, PA 19104; e-mail: [email protected]. Ó 2014 Pharmacotherapy Publications, Inc.
Previous guidelines classified a CHADS2 score of 2 or higher as high risk for stroke and recommended vitamin K antagonist (VKA) therapy; a CHADS2 score of 1 was considered intermediate risk, with aspirin or VKA therapy as treatment options; and a CHADS2 score of 0 was considered low risk, with aspirin therapy preferred.2 The new guideline–recommended therapy is based on the CHA2DS2-VASc score. No therapy is recommended for patients with a CHA2DS2VASc of 0.1 Patients with a CHA2DS2-VASc score of 1 may receive no therapy or aspirin, VKA (specifically warfarin), or NOAC therapy; all patients with scores 2 or above should receive anticoagulation with either warfarin or an NOAC.1 The new guidelines assume that basing anticoagulation therapy decisions on CHA2DS2-VASc scoring maintains the same benefit-risk ratio observed in clinical trials that utilized CHADS2 scoring. In addition, the adoption of CHA2DS2VASc to assess stoke risk will result in more patients qualifying for anticoagulation therapy. The greatest impact will be seen in patients who would have been scored 0 or 1 when using CHADS2 scoring. Results from a nationwide cohort study conducted in Denmark evaluated stroke and thromboembolism rates in patients scored as CHADS2 0 or 1.3 Of the patients with a CHADS2 score of 0, ~21% (4169 of 19,444 patients) would have had a CHA2DS2-VASc score of 2 or higher; of the patients with a CHADS2 score of 1, ~92% (25,809 of 28,132 patients) would have had a CHA2DS2-VASc score of 2 or higher. This serves to highlight just
2
PHARMACOTHERAPY Volume **, Number **, 2014
how many additional patients may be treated with more aggressive therapy when the new guidelines are used. Treating additional patients based on CHA2DS2-VASc will, in theory, decrease the number of cardioembolic strokes. However, bleeding risk scores such as HASBLED (hypertension, abnormal renal or liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age 65 yrs or older], or concomitant drug [antiplatelets or nonsteroidal antiinflammatory drugs] or alcohol use) are not endorsed by the newest guidelines.1 Making therapy decisions for the increased number of patients eligible for anticoagulation treatment without an objective way to assess bleeding risk could lead to more clinically significant bleeds. The new guidelines recommend NOAC therapy for patients who are “unable to maintain a therapeutic INR level with warfarin.” Some may interpret this as a simple solution to a situation that is often complex. It is important to identify the reasons that patients are unable to maintain a therapeutic INR while taking warfarin. Patient noncompliance or nonadherence is often a reason for the difficulty in maintaining a therapeutic INR. Patients who are intermittently compliant with VKA therapy may not be the best candidates for NOAC therapy and might actually have an increased risk of stroke. Patients who miss a couple of days of VKA therapy may still have a therapeutic INR, but given the short half-lives of the newer agents, missing a couple doses of an NOAC could result in subtherapeutic anticoagulation. For other patients, the barrier to maintaining a therapeutic INR is unwillingness or inability to undergo frequent INR monitoring. In the Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study that compared apixaban with aspirin in patients who were unsuitable for VKA therapy, 43% of patients were included because their “INR could not or was unlikely to be measured at the required intervals.”4 Having the guidelines recommend NOAC therapy for patients “unable to maintain a therapeutic INR level with warfarin” may have a negative impact on patient outcomes. Patients receiving VKA therapy have frequent visits (at least monthly) with a care provider to monitor their INR, which gives the provider the opportunity to assess patients’ bleeding risks and to reinforce and educate
patients on the importance of adherence to their anticoagulation therapy. Patients receiving NOACs miss out on this extra interaction with the health care team. As stated in the new guidelines, certain patient populations are not suited for therapy with NOACs. All of the new agents are renally eliminated and therefore contraindicated in patients with end-stage renal disease.1 In addition, patients with mechanical heart valves were shown to have increased thromboembolic and bleeding complications with dabigatran over warfarin in one study.5 Until convincing data show otherwise, NOACs should be avoided in patients with mechanical valves.1 However, the guidelines do not offer anticoagulation recommendations for all patient populations commonly encountered in clinical practice, such as those with hepatic dysfunction or patients with extremes of weight.1 These populations have historically been underrepresented in clinical trials. Until substantially more evidence and experience with NOACs is available, VKA therapy should remain the treatment of choice for many patients because efficacy and safety of anticoagulation therapy can be continually assessed with careful INR monitoring. Limited data are now available to help guide the clinician in one of the more common clinical conundrums when treating patients with atrial fibrillation: which antithrombotic regimen to choose in the patient with atrial fibrillation and coronary artery disease who has recently received a coronary stent, particularly a drugeluting stent. Because these patients require dual oral antiplatelet therapy with aspirin and a P2Y12 receptor antagonist (clopidogrel, prasugrel, or ticagrelor), the addition of an anticoagulant can put the patient at a substantially increased risk of bleeding events.6 Although the limited data suggest the safety and efficacy of using clopidogrel and warfarin without aspirin in this setting,7 additional data would be required before this strategy could be recommended for all cases. The guidelines generically mention that it might be reasonable to use clopidogrel concurrently with “anticoagulants” in this patient population,1 but it should be noted that the supporting data are only with warfarin and not the newer agents.7 Data are also lacking for the use of NOACs with the newer P2Y12 receptor antagonists (prasugrel and ticagrelor). Because of the more potent platelet inhibition with these agents over clopidogrel, data with clopidogrel and NOACs should not be extrapolated to the
EDITORIAL: ATRIAL FIBRILLATION GUIDELINES Charneski new P2Y12 receptor antagonists; therefore, concomitant use should be avoided. One of the limitations of the new guidelines is that they fail to clearly address the role for dual antiplatelet therapy for stroke prevention in patients with atrial fibrillation. The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-A) trial compared clopidogrel plus aspirin versus aspirin alone in patients with atrial fibrillation who were not candidates for warfarin.8 Although the clopidogrel plus aspirin group experienced an increase in major bleeding events (2%/yr vs 1.3%/yr, p
KEY WORDS atrial fibrillation, arrhythmia, guidelines, anticoagulation, stroke. (Pharmacotherapy 2014;**(**):**–**) doi: 10.1002/phar.1498
Updated treatment guidelines for the management of patients with atrial fibrillation were recently released by the American College of Cardiology/American Heart Association Task Force.1 Although ventricular rate control and anticoagulation still remain the cornerstone of treatment for most patients, several changes set forth in these guidelines will likely have a major impact on the care of patients with atrial fibrillation. Switching from the CHADS2 scoring system (1 point each for congestive heart failure, hypertension, age 75 years or older, or diabetes mellitus, and 2 points for previous stroke or transient ischemic attack [TIA]) to CHA2DS2VASc (1 point each for congestive heart failure, hypertension, diabetes mellitus, vascular disease, age 65–74 years, or female sex, and 2 points each for age 75 years or older or previous stroke or TIA) for risk stratification and the emergence of the newer oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban contribute to most of the changes in the new guidelines, whereas optimal heart rate targets remain controversial.1, 2 The opinions expressed in this editorial are those of the author and do not necessarily represent the position of Pharmacotherapy or the American College of Clinical Pharmacy. Invited editorials are not peer reviewed. *Address for correspondence: Lisa Charneski, Associate Professor of Clinical Pharmacy, Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy at University of the Sciences, 600 S. 43rd Street, Box 34, Philadelphia, PA 19104; e-mail: [email protected]. Ó 2014 Pharmacotherapy Publications, Inc.
Previous guidelines classified a CHADS2 score of 2 or higher as high risk for stroke and recommended vitamin K antagonist (VKA) therapy; a CHADS2 score of 1 was considered intermediate risk, with aspirin or VKA therapy as treatment options; and a CHADS2 score of 0 was considered low risk, with aspirin therapy preferred.2 The new guideline–recommended therapy is based on the CHA2DS2-VASc score. No therapy is recommended for patients with a CHA2DS2VASc of 0.1 Patients with a CHA2DS2-VASc score of 1 may receive no therapy or aspirin, VKA (specifically warfarin), or NOAC therapy; all patients with scores 2 or above should receive anticoagulation with either warfarin or an NOAC.1 The new guidelines assume that basing anticoagulation therapy decisions on CHA2DS2-VASc scoring maintains the same benefit-risk ratio observed in clinical trials that utilized CHADS2 scoring. In addition, the adoption of CHA2DS2VASc to assess stoke risk will result in more patients qualifying for anticoagulation therapy. The greatest impact will be seen in patients who would have been scored 0 or 1 when using CHADS2 scoring. Results from a nationwide cohort study conducted in Denmark evaluated stroke and thromboembolism rates in patients scored as CHADS2 0 or 1.3 Of the patients with a CHADS2 score of 0, ~21% (4169 of 19,444 patients) would have had a CHA2DS2-VASc score of 2 or higher; of the patients with a CHADS2 score of 1, ~92% (25,809 of 28,132 patients) would have had a CHA2DS2-VASc score of 2 or higher. This serves to highlight just
2
PHARMACOTHERAPY Volume **, Number **, 2014
how many additional patients may be treated with more aggressive therapy when the new guidelines are used. Treating additional patients based on CHA2DS2-VASc will, in theory, decrease the number of cardioembolic strokes. However, bleeding risk scores such as HASBLED (hypertension, abnormal renal or liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age 65 yrs or older], or concomitant drug [antiplatelets or nonsteroidal antiinflammatory drugs] or alcohol use) are not endorsed by the newest guidelines.1 Making therapy decisions for the increased number of patients eligible for anticoagulation treatment without an objective way to assess bleeding risk could lead to more clinically significant bleeds. The new guidelines recommend NOAC therapy for patients who are “unable to maintain a therapeutic INR level with warfarin.” Some may interpret this as a simple solution to a situation that is often complex. It is important to identify the reasons that patients are unable to maintain a therapeutic INR while taking warfarin. Patient noncompliance or nonadherence is often a reason for the difficulty in maintaining a therapeutic INR. Patients who are intermittently compliant with VKA therapy may not be the best candidates for NOAC therapy and might actually have an increased risk of stroke. Patients who miss a couple of days of VKA therapy may still have a therapeutic INR, but given the short half-lives of the newer agents, missing a couple doses of an NOAC could result in subtherapeutic anticoagulation. For other patients, the barrier to maintaining a therapeutic INR is unwillingness or inability to undergo frequent INR monitoring. In the Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study that compared apixaban with aspirin in patients who were unsuitable for VKA therapy, 43% of patients were included because their “INR could not or was unlikely to be measured at the required intervals.”4 Having the guidelines recommend NOAC therapy for patients “unable to maintain a therapeutic INR level with warfarin” may have a negative impact on patient outcomes. Patients receiving VKA therapy have frequent visits (at least monthly) with a care provider to monitor their INR, which gives the provider the opportunity to assess patients’ bleeding risks and to reinforce and educate
patients on the importance of adherence to their anticoagulation therapy. Patients receiving NOACs miss out on this extra interaction with the health care team. As stated in the new guidelines, certain patient populations are not suited for therapy with NOACs. All of the new agents are renally eliminated and therefore contraindicated in patients with end-stage renal disease.1 In addition, patients with mechanical heart valves were shown to have increased thromboembolic and bleeding complications with dabigatran over warfarin in one study.5 Until convincing data show otherwise, NOACs should be avoided in patients with mechanical valves.1 However, the guidelines do not offer anticoagulation recommendations for all patient populations commonly encountered in clinical practice, such as those with hepatic dysfunction or patients with extremes of weight.1 These populations have historically been underrepresented in clinical trials. Until substantially more evidence and experience with NOACs is available, VKA therapy should remain the treatment of choice for many patients because efficacy and safety of anticoagulation therapy can be continually assessed with careful INR monitoring. Limited data are now available to help guide the clinician in one of the more common clinical conundrums when treating patients with atrial fibrillation: which antithrombotic regimen to choose in the patient with atrial fibrillation and coronary artery disease who has recently received a coronary stent, particularly a drugeluting stent. Because these patients require dual oral antiplatelet therapy with aspirin and a P2Y12 receptor antagonist (clopidogrel, prasugrel, or ticagrelor), the addition of an anticoagulant can put the patient at a substantially increased risk of bleeding events.6 Although the limited data suggest the safety and efficacy of using clopidogrel and warfarin without aspirin in this setting,7 additional data would be required before this strategy could be recommended for all cases. The guidelines generically mention that it might be reasonable to use clopidogrel concurrently with “anticoagulants” in this patient population,1 but it should be noted that the supporting data are only with warfarin and not the newer agents.7 Data are also lacking for the use of NOACs with the newer P2Y12 receptor antagonists (prasugrel and ticagrelor). Because of the more potent platelet inhibition with these agents over clopidogrel, data with clopidogrel and NOACs should not be extrapolated to the
EDITORIAL: ATRIAL FIBRILLATION GUIDELINES Charneski new P2Y12 receptor antagonists; therefore, concomitant use should be avoided. One of the limitations of the new guidelines is that they fail to clearly address the role for dual antiplatelet therapy for stroke prevention in patients with atrial fibrillation. The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-A) trial compared clopidogrel plus aspirin versus aspirin alone in patients with atrial fibrillation who were not candidates for warfarin.8 Although the clopidogrel plus aspirin group experienced an increase in major bleeding events (2%/yr vs 1.3%/yr, p
