Discussed by Dr. Alan D. Kramer, M.D., F.A.C.C.
The findings of the AFFIRM study (Atrial Fibrillation Follow-up Investigation of Rhythm Management) have required cardiologists to take a fresh look at the treatment of atrial fibrillation (AF), which, according to the American Heart Association affects 2.2 million Americans. About 15 percent of strokes occur in people with atrial fibrillation.
Clinical cardiologist Dr. Alan D. Kramer said the study, involving about 5,000 patients randomized into two arms, compared rhythm control (maintaining sinus rhythm) to rate control.
"The study found that patients did as well in either arm of the study with a trend toward higher mortality in the rhythm control arm. This is important because cardiologists have traditionally tried to convert (atrial fibrillation patients) to sinus rhythm, thinking longevity would be affected. This has turned out not to be the case."
Dr. Kramer noted that all patients in both arms of the study were on Coumadin.
The indication for cardioversion for AF is for symptomatic patients with shortness of breath, dizziness, chest pain and palpitations. The following drug treatments are used to maintain sinus rhythm. Class I-C drugs, including flecanide and propafenone, are used if there is no structural heart disease. Class III drugs such as amiodarone and sotalol are used if structural heart disease is present.
The beta-blocker class of drugs remains the best choice for rate control, according to Dr. Kramer, with other options being Cardizem, digoxin and Verapamil.
Anti-coagulation for AF
"Coumadin is the mainstay of treatment for AF with risk factors for stroke. The more risk factors patients have, the more likely they will have an embolic event," Dr. Kramer said. Those risk factors, represented by the mnemonic CHADS, are:
- Congestive Heart Failure
- Age greater than 65
- Stroke or prior embolic events (a factor worth two points)
Echo findings that indicate increased risk are:
- Enlarged left atrium
- Left ventricular systolic dysfunction
- Left atrial smoke
The importance of anticoagulation in the management of AF is reflected in the fact that two thirds of patients presenting with stroke were either subtherapeutic or off Coumadin.
"The INR (International Normalization Rate) range for AF patients on Coumadin is 2 to 3. A recent study showed no strokes occurred in patients with INR between 2.5 and 3. Few strokes occurred in patients with a range between 2-2.5," Dr. Kramer said.
New drug therapies
The Food and Drug Administration is nearing approval of Ximelagatran, a direct thrombin inhibitor that could replace Coumadin (warfarin), the current standard. A series of Phase III studies known as Stroke Prevention using an Oral Thrombin Inhibitor in Atrial Fibrillation V (SPORTIF V) found that Ximelagatran is as effective as warfarin in patients with atrial fibrillation, Dr. Kramer said.
Dosing will be BID and no coagulation monitoring is necessary. A potential problem is that liver function tests are affected in a small percentage, specifically elevations of serum alanine aminotranferase enzyme. These elevations have been largely asymptomatic and have reverted to normal with or without discontinuing the drug. However, some liver monitoring, especially during the early course of treatment, will likely be advised for patients on Ximelagatran.
Among newer treatments for AF, Dr. Kramer cited a percutaneous technique to occlude the left atrial appendage as showing initial promise. The appendage has been occluded surgically in the past during CABG and valve surgery. Older treatments include the Maze procedure.
"Three to 5 percent of young patients with recurrent lone AF, which acts like focal atrial tachycardia, could be treated with pulmonary vein ablation," Dr. Kramer said.
"If the rate in AF is difficult to control, the option of AV ablation followed by implantation of VVIR pacer exists." Newer data, he said, indicate that the reason these patients don't respond to AV nodal blocking drugs is that they have a small, compact AV node, which limits exposure to drug therapy.
- The AFFIRM study has shown that AF patients do as well on rate control therapies as on rhythm control therapies.
- Coumadin remains the mainstay for treatment of AF with risk factors.
- Ximelagatran, a direct thrombin inhibitor now nearing FDA approval, may become the new standard for treatment of AF.
- A percutaneous technique to occlude the left atrial appendage is showing initial promise as a new treatment for AF.