Atrial Fibrillation, Bleeding and Stroke
Dilip Elangbam, MD, CMD, FACP
Jane is an 85-year-old lady who lives alone. She fell and could not get up by herself. Her neighbor found her laying on the floor. The whole of the left side of the body was black and blue. She was admitted to the hospital, deemed not fit to live alone, and now admitted to a long-term living facility. She was taking Coumadin for atrial fibrillation.
Atrial fibrillation is fairly common in elder population, and unfortunately is always associated with fairly complex medical comorbidities. Geriatricians and providers in post-acute the long-term care specialty have to resume the role of cardiologist, endocrinologist, neurologist, nephrologist, hematologist and pharmacist. And
the rest of it. If you remember, in early1990s , it was a question of aspirin or Warfarin for someone with atrial fibrillation. Stroke being the final endpoint of the disease spectrum. Warfarin was a dreaded word - rat poison with bleeding complications, going to anticoagulation clinic all four seasons, every month if you are lucky and drug interactions with anything you are taking. Bruised skin, gastrointestinal bleeding, blood transfusion are
on higher scale of complications. If there is any possible risk of bleeding, we always opted for aspirin and convinced ourselves why Warfarin is not a choice. It was a skill of gut feeling, doing the right thing.
Sooner, aspirin was found not to be effective to prevent stroke, and was no more an option.
Who really needs Warfarin?
CHA2DS2-VASc score was born ( earlier version is CHADS2). This will determine who will benefit from taking anticoagulants. Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, Stroke/TIA, Vascular disease, Age 65-74 years, and Sex being the driving forces in this equation. Each condition is given a score of one point, except age 75 years or above and stroke, valued two points each. The maximum score is nine. As the score goes up, risk of stroke goes up, roughly 16 percent with highest score of nine and three percent with a score of three. Anyone with lone atrial fibrillation, with a score of 0 points in this score does not need anticoagulation. This has been a very popular tool and has been found useful in other cardiac evaluations, more so in preoperative cardiac evaluations. Any trial on atrial fibrillation should use this score, however, it is poor in predicting any of the bleeding complications.
"Comparative Validation of Novel Risk Score for Predicting Bleeding Risk in Anticoagulated Patients with Atrial Fibrillation: The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score,” a paper by Dr Gregory Y H Lip et al, was published in the Journal of American College of Cardiology, 2011 January issue. This has been a very valuable clinical tool. Of the nine conditions, five can be modified or controlled - hypertension, labile INR, bleeding tendency, drugs, and alcohol. This predictive score was validated during the study involving some 7000 patients with atrial fibrillation in the SPORTIF (Stroke Prevention Using an ORal Thrombin Inhibitor in Atrial Fibrillation) clinical trials.
"The Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED Bleeding Risk-Prediction Scores in Patients with Atrial Fibrillation Undergoing Anticoagulation: The AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients with Atrial Fibrillation) Study," a paper by Stavros Apostolakis et al published in the Journal of American, Cardiology, 2012 August issue used three methods of predicting major bleeding. The HAS -BLED score outperformed other risk prediction scores in patients with atrial fibrillation undergoing anticoagulation - HEMORR(2) HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation). The performance was modest at the best, and only the HAS- BLED score demonstrated significant predictive performance for intracranial bleeding. In addition, its simplicity earned recognition from subsequent trials
Below, stroke and bleeding risk stratification with the CHA2DS2-VASc and HAS -BLED schemas from “Use of the CHA2DS2-VASc and HAS-BLED Scores to Aid Decision Making for Thromboprophylaxis in Nonvalvular Atrial Fibrillation,” a study by Deirdre Lane et al published in Circulation, August 2012.
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The American College of Cardiology also offers a free app entitled AnticoagEvaluator, which calculates these scores as well as creatinine clearance based on four parameters - Age, Sex, Weight, and Serum Creatinine. I personally find it very valuable during busy clinic hours.
Mr. Simpson is 75 years old, has slate gray colored skin, and takes amiodarone. There are plenty of drug-drug interactions. He sees an ophthalmologist once a year to make sure there are no corneal deposits. Thyroid test, renal panel, and liver function tests are done on regular basis. Pulmonary function test and chest x ray are done every year or earlier if symptomatic. If there is scarring or pulmonary fibrosis, stopping the medicine is the best approach. So early detection is important. In summary, it is a fairly dangerous drug which is now used very commonly for atrial fibrillation. The goal of the treatment for atrial fibrillation was rate control and anticoagulation. Attempts with cardioversion are made earlier to bring back to sinus rhythm. Chemical cardioversion became more prevalent, and amiodarone earned its place. FDA also approved cardiac ablation when sinus rhythm cannot be achieved. This procedure is commonly performed by electrophysiologists in large numbers.
Now a decade later.
"Evaluation of the Age, Biomarkers, and Clinical History- Bleeding Risk Scores in Patients With Atrial Fibrillation With Combined Aspirin and Anticoagulation Therapy Enrolled in the ARISTOLE and RE-LY Trials." This original investigation is authored by Dr. Ziad Hijazi et al and was published in JAMA Network on September 16, 2020. This study examined a total of 24,349 patients with atrial fibrillation from two randomized clinical trials. This also introduced recently developed ABC (Age, Biomarkers, and Clinical History) - bleeding risk score for patients with atrial fibrillation.
ARISTOLE (Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation) study was done between 2006 and 2010, with total enrollment of 14,980 patients with atrial fibrillation. Between 2005 and 2009 in the RE-LY( Randomized Evaluation of Long-term Anticoagulation Therapy) study, 9,369 patients were enrolled. Out of the robust data from this study, one thing was very clear. In the days of precision medicine, ABC-bleeding risk score is the clear winner. This is now even included in European AF and Dual Antiplatelet Therapy guidelines as a possible tool to estimate risk of major bleeding in patients with atrial fibrillation. It even outperformed HAS -BLED risk score. ABC- bleeding risk score biomarkers include growth differentiation factor -15 (GDF-15), and high sensitive cardiac troponin T and N- terminal prohormone of brain natriuretic peptide(NT-proBNP) levels. This is commercially available from Roche Diagnostics.
The landmark non -vitamin K antagonist oral anticoagulants( NOAC) trials have shown the lower risks of major bleeding in comparison with patients taking coumadin. This has changed the landscape of anticoagulation in atrial fibrillation. NOACs have almost replaced coumadin. Of course, this comes with some price, there are no antidotes available to NOACs, unlike coumadin.
Paxlovid is available for treatment of COVID 19 infection, when symptomatic. It also has plenty of drug - drug interactions with almost all of the cardiac medications including NOACs. Metabolism of each of these new drugs are different, some of them are inducer, and could lead to higher bioavailability, causing unwanted side effects. Should we hold them while on Paxlovid or lower the dose? There is no good way of knowing it. Leave it to your pharmacist.
This year.
Annals of Internal Medicine has published an original research article in January edition of 2023, “Left Atrial Mechanical Dysfunction and Risk for Ischemic Stroke in People Without Prevalent Atrial Fibrillation or Stroke, a prospective Cohort Study led by Dr Ankit Maheshwari, MD. Left atrium enlargement is the hallmark in the diagnosis of atrial fibrillation in echocardiographic studies. Recently attention is to atrial myopathy. Fibrotic myocardial remodeling is the mechanism underlying the structural and functional change. Lower left atrial strain has been associated with higher degree of atrial fibrosis. In their study, significant number of patients had ischemic strokes, without atrial enlargement, or atrial fibrillation but had low left atrial strain. Is the ischemic stroke due to the dysrhythmia of atrial fibrillation versus the underlying atrial myopathy? This will be a thoughtful debate for years to come.
The Journal of Clinical Medicine published “Prospective Assessment of Cerebral Microbleed with Low Field Magnetic Resonance Imaging (0.55 Tesla MRI)” by Dr. Thilo Rusche et al. in February 2023. Cerebral microbleeds (2-10 mm in diameter) on MRI are subgroups of ischemic stroke patients with atrial fibrillation with high intracranial bleeding risk. Its prevalence has been somewhere between seven to 30 percent.
The present study shows no significant differences in overall image quality and diagnostic quality between
low field MRI at 0.55 Tesla and 1.5 Tesla scanners. They have similar accuracy in detecting cerebral microbleeds. This is a great potential as a resource - efficient alternative in the near future. This concept is somewhat comparable to low dose CT scan for detection of lung cancer.
In summary, it is not too much to say, evaluation of atrial fibrillation starts with plain old EKG, CHA2DS2-VASc, ABC-bleeding score, Echocardiography with left atrium strain, and low field MRI of brain.
My neighbor John also has atrial fibrillation and diabetes mellitus. He is 75 years old. He lives alone, drives his Mercedes, cooks for himself, and has a very active lifestyle. He wears a fit bit and an alarm. His son visits him every Christmas. He has never fallen, that I know of. He is a member of our local ambulance. His social security has an eight percent raise this year. Without copay, he pays $ 4.00 a gallon for gas, $6.00 for a dozen of eggs, $800.00 for a month's supply of Eliquis, and $900.00 for Ozempic. Life is good.
Any views or opinions presented in this article are solely those of the author and do not necessarily represent any policy or position of PAMED, PMDA, AMDA, its affiliates, and members.
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