AF atrial fibrillation

These studies have found no significant differences in mortality in patients who received rhythm control therapy versus those who received rate control therapy.29-32 Howevei;patients assigned to the rhythm control strategy were more likely to be hospitalized^-31-32 and were more likely to experience adverse effects associated with

29 30

drug therapy. ■ Therefore, drug therapy for the purpose of maintaining sinus rhythm or reducing the frequency of episodes of AF should be initiated only in those patients with episodes of paroxysmal AFwho continue to experience symptoms despite maximum tolerated doses of drugs for ventricular rate control. A decision strategy for maintenance therapy of sinus rhythm is presented in Figure 9-8. Drug therapy for maintenance of sinus rhythm and/or reduction in the frequency of episodes of paroxysmal AF should not be initiated in patients with underlying correctable causes of AF, such as hyperthyroidism; rather, the underlying cause of the arrhythmia should be corrected.

Stroke Prevention. All patients with paroxysmal, persistent, or permanent AF should receive therapy for stroke prevention unless compelling contraindications exist. A number of decision strategies for assigning patients to receive anticoagulation for stroke prevention in AF have been suggested; two commonly used strategies are

presented in Tables 9-10 and 9-11. In general, most patients require therapy with warfarin; in some patients with no or few additional risk factors for stroke, aspirin may be acceptable. For some patients, serious consideration of the benefits of warfarin versus the risks of bleeding associated with warfarin therapy is warranted. The potential bleeding risks associated with warfarin may outweigh the benefits in patients with a pretreatment INR of greater than 2, alcoholism, anticipated poor compliance, a history of falls, or current bleeding diathesis. In these situations, patients are at risk of severe bleeding associated with warfarin, including intracerebral hemorrhage, which may be associated with consequences as serious as those associated with a thrombotic stroke, and aspirin therapy may be associated with a more favorable benefit: risk ratio.

FIGURE 9-8. Decision algorithm for maintenance of sinus rhythm/reduction in the frequency of episodes of atrial fibrillation. (CAD, coronary artery disease; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy.)

Recently, specific genetic tests to guide the initiation of warfarin therapy have been approved by the FDA. These tests assess single nucleotide polymorphisms on the gene that encodes cytochrome P-450 2C19, the primary hepatic enzyme responsible for warfarin metabolism, and the gene VKORC1, which encodes vitamin K epoxide reductase, the enzyme that is inhibited by warfarin as its mechanism of anticoagulation. Some advocate that all patients in whom warfarin therapy is being initiated should undergo genetic testing to guide the initiation of therapy; patients with specific polymorphisms of one or both of these genes may require adjustment of the initial warfarin dose to achieve adequate anticoagulation or avoid overanticoagulation and toxicity. Genetic testing to guide the initiation of warfarin therapy has not yet become standard practice, and many have questioned the efficacy and cost effectiveness of incorporation of routine genetic testing into warfarin therapy. The role of genetic testing in selecting initial warfarin doses may continue to evolve, but at the present time, appears to be limited.

Table 9-10 American College of Chest Physicians Recommendations for Stroke Prevention in AF

Patient Category {Risk Factors}

Recommended Drug

Dose/Target

Prior ischemic stroke, TIA, of iystemic embolism

Two or more of the following: Age greater than

75 years Hypertension Diabetes rmellilus Heart failure

One of the following: Age greater than

75 years Hypertension Did betes mellitus Heart failure

VV.-Vfi'in

Warfarin or aspirin; INR 2,5

however, guidelines {range 2 3)

strongly recommend 75 ^325 rng orally warfarin in this daily population

Less than 75 years of Aspirir age and no othei risk factors for ischemic stroke

75-325 mg orally daily

AF, atrial fibrillation; INRr International Normalized Ratio; TIAr transient ischemic attack.

Table 9-11 Drugs for Stroke Prevention in AF—CHADS2 Risk Stratification

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