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Q & A With the Expert on: Atrial Fibrillation
Q: Should a 78-year-old woman with atrial fibrillation with hypertension, diabetes, prior heart failure, and prior stroke without contraindications to warfarin be treated with warfarin or aspirin? If warfarin, to what international normalized ratio?
Case Presentation
A 78-year-old functionally independent woman has had hypertension and diabetes mellitus for the past 1 year. Six months ago, she developed congestive heart failure (CHF) precipitated by an episode of paroxysmal atrial fibrillation (AF), with an average ventricular rate of 165 beats per minute, which resolved after direct-current cardioversion of the AF to sinus rhythm. A 2-dimensional echocardiogram at that time revealed a left ventricular ejection fraction (LVEF) of 35%. Three months ago, she developed a thromboembolic stroke with left hemiparesis, which resolved in 1 week. An electrocardiogram at that time revealed AF, which has persisted. Her current medications include glyburide 5 mg daily, hydrochlorothiazide 25 mg daily, ramipril 10 mg twice daily, simvastatin 40 mg daily, aspirin 325 mg daily, and digoxin 0.25 mg daily. Physical examination in her physician’s office revealed a blood pressure in the sitting and standing positions in the right brachial artery of 136/80 mm Hg and of 134/82 mm Hg in the left brachial artery, a grossly irregular pulse with a rate of 106 per minute, and a respiratory rate of 16 per minute. Physical examination was normal except for a grossly irregular cardiac rhythm with an average ventricular rate of 114 per minute.
The patient’s fasting blood sugar was 98 mg/dL, hemoglobin A1c was 6.8%, serum total cholesterol was 143 mg/dL, serum low-density lipoprotein cholesterol was 69 mg/dL, serum high-density lipoprotein cholesterol was 50 mg/dL, and her serum triglycerides were 120 mg/dL. Her hemoglobin, hematocrit, and thyroid function tests were normal.
How should this patient have her AF managed?
A: This patient needs the addition of a beta blocker such as metoprolol or carvedilol to slow her rapid ventricular rate associated with AF.1 Oral verapamil and diltiazem also could slow her rapid ventricular rate but are contraindicated because of her abnormal LVEF. The addition of a beta blocker to her angiotensin-converting enzyme inhibitor ramipril will also increase her LVEF. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the American Diabetes Association recommend reducing the blood pressure to less than 130/80 mm Hg in patients with diabetes mellitus. The addition of a beta blocker such as carvedilol to her antihypertensive regimen of hydrochlorothiazide plus ramipril should achieve that goal.
On the basis of data from trials such as the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study,2 the case patient should be treated with ventricular rate control plus warfarin therapy to maintain an international normalized ratio (INR) of 2.0-3.0, rather than with an attempt to maintain sinus rhythm with antiarrhythmic drugs after cardioversion to sinus rhythm plus the use of warfarin. In this randomized study of 4060 patients (39% women; mean age, 70 yr) as compared with ventricular rate control plus warfarin, the maintenance of sinus rhythm plus warfarin therapy group had an insignificant increase in all-cause mortality at 5-year follow-up from 21% to 24%, an insignificant increase in thromboembolic stroke from 5.5% to 7.1%, a significant increase in hospitalization from 73% to 80%, and no difference in quality of life or functional status.2
The CHADS2 score is a validated predictive instrument used to assess stroke risk in patients with AF in the general population.3 It gives 1 point for age older than 75 years, 1 point for hypertension, 1 point for diabetes mellitus, 1 point for CHF, and 2 points for prior stroke or transient ischemic attack. The risk of stroke per year is 1.9% for a score of 0, 2.8% per year for a score of 1, 4.0% per year for a score of 2, 5.9% per year for a score of 3, 8.5% per year for a score of 4, 12.5% per year for a score of 5, and 18.2% per year for a score of 6.3 Since the case patient has a CHADS2 score of 6, her risk of stroke is 18.2% per year, and she should be treated with warfarin to maintain an INR between 2.0 and 3.0.
In the European Atrial Fibrillation Trial4 involving patients with recent transient cerebral ischemic attack or minor ischemic stroke, at 2.3-year follow-up the incidence of new thromboembolic events was 12% in patients treated with placebo, 10% in patients treated with aspirin, and 4% in patients treated with warfarin.4 In the Stroke Prevention in Atrial Fibrillation Study III,5 patients with AF considered to be at high risk for developing thromboembolic stroke were randomized to warfarin to achieve an INR between 2.0 and 3.0 versus aspirin 325 mg daily plus warfarin to achieve an INR between 1.2 and 1.5.5 Adjusted-dose warfarin to achieve an INR between 2.0 and 3.0 caused at 1.1-year follow-up a 72% significant reduction in thromboembolic stroke or systemic embolism (absolute reduction of 6.0%).5 Nonrandomized observational data from nursing home patients (mean age, 83 yr) found that 141 patients with AF treated with warfarin to achieve an INR between 2.0 and 3.0 had a 67% significant reduction in thromboembolic stroke as compared with 209 patients with AF treated with aspirin 325 mg daily.6
In conclusion, I would stop aspirin in the case patient and substitute oral warfarin in a dose to maintain an INR between 2.0 and 3.0. I would add oral carvedilol in a dose to slow the rapid ventricular rate associated with her AF, reduce her blood pressure to a level recommended for persons with diabetes, and improve her LVEF. Her other medications should not be changed.
The author reports no relevant financial relationships.
From the Department of Medicine, Divisions of Cardiology, Geriatrics, and Pulmonary/Critical Care, New York Medical College, Valhalla, NY.
