Case 1: Anticoagulants for atrial fibrillation after percutaneous coronary intervention
An 81-year-old man is evaluated in the office 3 days following a percutaneous coronary intervention with placement of a bare metal stent in the left anterior descending artery for angina refractory to maximal medical therapy. He indicates that he feels well except for palpitations that were not present before the procedure. Medical history is significant for hypertension and type 2 diabetes mellitus. He has no risk factors for or history of significant bleeding. Medications are aspirin, clopidogrel, lisinopril, atorvastatin, and metformin.
On physical examination, the patient is afebrile, blood pressure is 110/60 mm Hg, pulse rate is 65/min, and respiration rate is 12/min. BMI is 32. Estimated central venous pressure is not elevated. The heart has an irregularly irregular rhythm. Lungs are clear without crackles.
An electrocardiogram shows atrial fibrillation with a heart rate of 65/min and no acute ischemic changes. An echocardiogram demonstrates a left ventricular ejection fraction of 30%.
Which of the following is the most appropriate therapeutic regimen for this patient?
A. Aspirin and clopidogrel
B. Aspirin and dabigatran
C. Aspirin and warfarin
D. Aspirin, clopidogrel, and warfarin
Case 2: Periprocedural anticoagulation
A 63-year-old man is scheduled for recommended repeat colonoscopy in follow-up of adenomatous polyps detected on screening 3 years ago. Medical history is significant for an unprovoked pulmonary embolism 5 years ago. He was initially treated with warfarin but switched to rivaroxaban 1 year ago because of fluctuating INR values with warfarin. He is otherwise healthy and has had no bleeding.
Laboratory studies show a normal complete blood count and a serum creatinine level of 0.8 mg/dL (70.7 µmol/L).
Which of the following is the most appropriate management of this patient's anticoagulation for undergoing colonoscopy?
A. Continue rivaroxaban without interruption
B. Stop rivaroxaban 1 day before colonoscopy without bridging
C. Stop rivaroxaban 1 day before colonoscopy and bridge with low-molecular-weight heparin
D. Stop rivaroxaban 5 days before colonoscopy without bridging
E. Stop rivaroxaban 5 days before colonoscopy and bridge with low-molecular-weight heparin
Case 3: Stroke and atrial fibrillation
A 57-year-old woman is evaluated in the emergency department 24 hours after new onset of left hemiparesis and left hemineglect. The patient has hypertension and functional class II New York Heart Association nonischemic heart failure. Medications are enalapril, furosemide, and metoprolol.
On physical examination, temperature is normal, blood pressure is 166/78 mm Hg, pulse rate is 68/min and irregular, and respiration rate is 12/min. A cough is noted. Cardiac examination confirms an irregularly irregular heart rhythm. Neurologic examination shows left visual and tactile extinction, left facial weakness, dysarthria, left arm and leg weakness (muscle strength, 4/5), and normal orientation and language function. She is unable to safely swallow water but can swallow thickened liquids.
Results of laboratory studies are notable for an INR of 1.1 and a serum LDL cholesterol level of 54 mg/dL (1.40 mmol/L).
A CT scan of the head shows an acute infarction in the right parietal and frontal lobes involving half of the hemisphere. An electrocardiogram (ECG) shows atrial fibrillation; an ECG obtained 1 year ago was normal. An echocardiogram shows a left ventricular ejection fraction of 50% without valvular disease or wall motion abnormalities. A chest radiograph and a carotid ultrasound show normal findings.
Which of the following is the most appropriate next step in treatment?
C. Intravenous heparin
Case 4: Perioperative care with a prosthetic valve
A 58-year-old man is seen for preoperative evaluation prior to umbilical hernia repair scheduled in 1 week. He has been in good health except for increasing pain at the site of his umbilical hernia. He has experienced no incarceration of his hernia. He exercises regularly without symptoms. He has no history of stroke or transient ischemic attack. Medical history is notable for aortic valve replacement with bileaflet mechanical prosthesis performed 3 years ago for a bicuspid aortic valve and decreasing exercise capacity. Medications are warfarin and low-dose aspirin.
On physical examination, blood pressure is 124/72 mm Hg, and pulse rate is 70/min. Cardiovascular examination reveals a regular rhythm, a mechanical S2, and a grade 1/6 early systolic crescendo-decrescendo murmur at the cardiac base without radiation.
Laboratory studies show a normal serum creatinine level.
An electrocardiogram performed 2 months ago showed normal sinus rhythm with normal intervals. An echocardiogram from 2 months ago showed normal left ventricular function and normal function of the mechanical aortic valve prosthesis.
In addition to continuing aspirin and stopping warfarin 5 days before surgery, which of the following is the most appropriate management for preoperative anticoagulation bridging?
A. Intravenous unfractionated heparin
B. Prophylactic-dose subcutaneous enoxaparin
C. Therapeutic-dose subcutaneous enoxaparin
D. No bridging anticoagulation
Case 5: Post-afib ablation
A 58-year-old woman is evaluated during a routine physical examination. She has a history of atrial fibrillation and had an atrial fibrillation ablation procedure 6 months ago. Before her ablation, she had persistent atrial fibrillation with palpitations and dyspnea. Since her ablation, she has been asymptomatic with no palpitations. Ambulatory electrocardiographic monitoring at 3 and 6 months after the ablation demonstrated no atrial fibrillation. Medical history is also significant for a transient ischemic attack, hypertension, and hyperlipidemia. Her medications are warfarin, metoprolol, candesartan, and simvastatin.
On physical examination, the patient is afebrile, blood pressure is 130/80 mm Hg, pulse rate is 64/min, and respiration rate is 16/min. BMI is 30. Heart rate and rhythm are regular.
An electrocardiogram shows normal sinus rhythm.
Which of the following is the most appropriate management?
A. Continue warfarin
B. Continue warfarin and add aspirin
C. Discontinue warfarin
D. Discontinue warfarin and start aspirin
E. Discontinue warfarin and start aspirin and clopidogrel
Answers and commentary
Correct answer: D. Aspirin, clopidogrel, and warfarin.
This patient should be treated with aspirin, clopidogrel, and warfarin (“triple therapy”). He has new-onset atrial fibrillation in the setting of recent bare metal stent placement for medically refractory angina. Patients with a bare metal stent should be treated with dual antiplatelet therapy for at least 1 month to allow endothelialization of the stent; with drug-eluting stents, the requirement for dual antiplatelet therapy is longer and depends upon the type of stent implanted. This patient is also at high risk of thromboembolic disease associated with atrial fibrillation. He has a CHA2DS2-VASc score of 5 (2 points for age >75 years, 1 point each for diabetes mellitus, hypertension, and vascular disease). Therefore, oral anticoagulant therapy is also indicated. Although triple therapy with two antiplatelet agents and systemic anticoagulation is associated with a significant increase in bleeding risk, this regimen is appropriate treatment in this patient for at least 1 month until stent endothelialization can be assured, at which time he can be transitioned to only aspirin and an oral anticoagulant to decrease bleeding risk but provide adequate thromboembolic prophylaxis. If warfarin is used as an anticoagulant during triple therapy, careful maintenance of the INR within the recommended range of 2.0 to 2.5 in patients without mechanical valves may reduce the overall bleeding risk.
Aspirin and clopidogrel are inferior to oral anticoagulation for the prevention of stroke in patients with an indication for anticoagulation for thromboembolism prophylaxis in atrial fibrillation.
Treatment with aspirin and dabigatran is not optimal for two reasons. First, in the Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) trial, there was a numeric excess of myocardial infarctions observed with dabigatran. More importantly, no data are available regarding the efficacy of aspirin and dabigatran for the prevention of stent thrombosis following an acute coronary syndrome.
Treatment with dual antiplatelet therapy is indicated in all patients with a coronary stent, with the recommended duration based on the underlying condition and type of stent placed. Therefore, treatment with aspirin and warfarin does not optimally prevent acute stent occlusion in a patient with stent placement.
- Patients with atrial fibrillation and recent stent placement should be treated with appropriate systemic anticoagulation and antiplatelet therapy as determined by risk scoring and the type of stent placed.
Correct answer: B. Stop rivaroxaban 1 day before colonoscopy without bridging.
The patient should stop rivaroxaban, a new oral anticoagulant (NOAC), the day before his scheduled colonoscopy. Because polypectomy or biopsy of lesions may become necessary during this patient's colonoscopy, interruption of anticoagulation is suggested in patients who are not at high risk for thromboembolic events, which includes this patient, because his thrombotic event occurred more than 3 months ago. Compared with warfarin, it is not yet known at what residual drug level procedures and surgeries can be safely performed without undue bleeding risk in patients taking an NOAC. In the absence of clinical data about when to stop these drugs before surgery, the half-life of the anticoagulant is the most frequently used parameter to decide when to stop the drug. Reported half-lives are 14 to 17 hours for dabigatran, 7 to 11 hours for rivaroxaban, 8 to 14 hours for apixaban, and 5 to 11 hours for edoxaban. For surgical procedures with standard risk for bleeding, the NOAC should be discontinued 2 to 3 half-lives beforehand, and in procedures with high bleeding risk, 4 to 5 half-lives beforehand. Close attention to kidney function is needed, because kidney impairment leads to prolonged half-lives of the NOACs. In this patient with normal kidney function, stopping rivaroxaban 24 to 36 hours before the procedure would be appropriate.
Bridging with low-molecular-weight heparin (LMWH) is not indicated, because LMWHs have half-lives of 4 to 7 hours, not much shorter than the NOACs. Additionally, this patient is not at high risk for thromboembolism and would not need preprocedural bridging even if he were taking warfarin.
- The new oral anticoagulants should be stopped 24 to 36 hours before surgeries with standard risk for bleeding and 2 to 4 days before surgeries with a high risk for bleeding in patients with normal kidney function.
Correct answer: A. Aspirin.
Aspirin should be added to this patient's medication regimen. She has had an acute ischemic stroke and has atrial fibrillation. No other obvious causes of stroke are present, and she is beyond the treatment window for recombinant tissue plasminogen activator therapy. According to two large clinical trials, aspirin administered within 48 hours of ischemic stroke onset modestly reduces the risk of recurrent ischemic stroke within the first 2 weeks without significantly increasing the risk of intracerebral hemorrhage. Administration of aspirin no later than the end of the second day after a stroke is an accepted quality-of-care core metric in primary and comprehensive stroke centers.
Anticoagulation with warfarin or a newer anticoagulant, such as dabigatran, is required to manage this patient's long-term risk of cardioembolic stroke. Some experts will initiate warfarin within 24 hours of stroke onset in medically stable patients with a small infarction, but withholding anticoagulation for 4 days to 2 weeks is typically recommended for patients with moderate to large infarctions. Until that time, patients are managed with aspirin.
In the acute ischemic stroke setting, intravenous heparin was ineffective compared with aspirin in patients with cardioembolic stroke in a randomized clinical trial. Furthermore, this patient's infarct is large enough to be associated with a risk of hemorrhaging into the bed of the infarct within the first 2 weeks of stroke.
- In patients with acute ischemic stroke who are ineligible for recombinant tissue plasminogen activator therapy, aspirin should be administered within 48 hours of the stroke to reduce the risk of recurrent ischemic stroke.
Correct answer: D. No bridging anticoagulation.
This patient should stop warfarin 5 days before his umbilical hernia repair surgery but requires no bridging anticoagulation. He is scheduled for an invasive procedure with a moderate or high risk of bleeding and therefore requires discontinuation of warfarin for surgery. Cessation of warfarin 5 days before surgery is typically sufficient to assure a normalized INR for the procedure. For patients requiring stoppage of chronic anticoagulation, the necessity of bridging anticoagulation must then be determined based on the patient's thromboembolic risk. Contemporary mechanical aortic valve prostheses have a low (<5%) annual risk of thromboembolism, and guidelines recommend no anticoagulation bridging for patients with these prostheses if they are in sinus rhythm and have no additional risk factors for arterial thromboembolism. Perioperative aspirin continuation in a patient whose only indication for antiplatelet therapy is a mechanical valve prosthesis is a matter of debate. The American College of Chest Physicians and the American College of Cardiology/American Heart Association both suggest that aspirin be continued throughout surgery in any patient in whom the antithrombotic benefits outweigh the bleeding risks. If aspirin is continued, the additional bleeding risk it confers should be factored into the decision making regarding bridging anticoagulation.
Both intravenous unfractionated heparin and therapeutic-dose subcutaneous enoxaparin are not appropriate in this patient. Either is an acceptable form of bridging anticoagulation for patients at intermediate or high risk of thromboembolism, but for patients with low thromboembolism risk, the potential bleeding complications of bridging outweigh the possible thromboembolism prevention. For bridging-eligible patients, low-molecular-weight heparin (LMWH) is often preferred because it can be administered in the outpatient setting and does not require laboratory monitoring; however, no evidence suggests any difference in outcomes with LMWH or unfractionated heparin.
Prophylactic-dose subcutaneous enoxaparin is only an acceptable choice for perioperative anticoagulation bridging in intermediate-risk (5%-10% annual rate of thromboembolism) patients on warfarin for a history of venous thromboembolism. For other chronic anticoagulation indications (atrial fibrillation and mechanical heart valves), no data are available to suggest a benefit from prophylactic-dose LMWH.
- Bridging anticoagulation is not indicated for patients who stop chronic warfarin therapy before surgery and have a low annual risk of thromboembolism.
Correct answer: A. Continue warfarin.
This patient should continue taking warfarin. She has a history of symptomatic atrial fibrillation and is now symptom-free without evidence of recurrent atrial fibrillation after catheter ablation. However, patients with successful ablation and elimination of symptoms may have transient asymptomatic atrial fibrillation with continued risk for atrial fibrillation–associated thromboembolic disease. Therefore, current consensus recommendations counsel that stroke prevention therapy following atrial fibrillation ablation be based on risk factors and not rhythm status, with the preferred risk stratification tool being the CHA2DS2-VASc risk score, which has improved predictive ability relative to the CHADS2 score. The patient is a 58-year-old woman with a prior transient ischemic attack (TIA) and hypertension. Accordingly, her CHA2DS2-VASc risk score is 4 (2 points for TIA, 1 point for hypertension, and 1 point for female sex). Current guidelines advocate oral anticoagulation for any patient with nonvalvular atrial fibrillation and a CHA2DS2-VASc score greater than 1. She has a history of a central nervous system event, and her annual risk of stroke is high (greater than 5% annually). Therefore, she should be continued on anticoagulation with warfarin.
Concomitant aspirin therapy with warfarin is reserved for patients with active coronary artery disease. This patient has risk factors for atherosclerosis, but she does not have a history of coronary artery disease or acute coronary syndromes. The addition of aspirin to warfarin significantly increases the risk of bleeding.
Discontinuation of warfarin and substitution with aspirin or dual antiplatelet therapy is not correct. Aspirin is insufficient therapy for a patient at high risk of stroke. The Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W) trial compared warfarin with therapy with aspirin and clopidogrel and found that aspirin with clopidogrel was inferior to warfarin for stroke prevention with no statistically significant difference in bleeding.
Anticoagulation with a novel oral anticoagulant (such as dabigatran, rivaroxaban, or apixaban) could be considered; however, these agents have been associated with increased gastrointestinal bleeding compared with warfarin.
- Stroke prevention therapy after catheter ablation of atrial fibrillation should be based upon risk stratification, not heart rhythm status.