A 72-year-old man comes to the emergency department due to severe left lower leg pain and tingling that came on abruptly several hours ago and has since become increasingly painful. Medical history is significant for hypertension, type 2 diabetes mellitus, paroxysmal atrial fibrillation, and osteoarthritis. The patient has a 45-pack-year smoking history. Blood pressure is 142/80 mm Hg, and pulse is 112/min and irregular. On physical examination, the left lower extremity skin appears mottled and is cool to the touch. The distal pulses of the left leg are not palpable. There is a right carotid bruit. Which of the following medications could have best prevented this patient's acute condition?
CHA2DS2-VASc score for thromboembolic risk | |||
Risk criteria | Points | ||
C | Congestive heart failure | 1 | |
H | Hypertension | 1 | |
A2 | Age ≥75* | 2 | |
D | Diabetes mellitus | 1 | |
S2 | Stroke or TIA | 2 | |
V | Vascular disease (eg, PAD, prior MI) | 1 | |
A | Age 65-74* | 1 | |
Sc | Sex category female | 1 | |
Maximum score | 9 | ||
Total score | Generalized stroke risk | Antithrombotic therapy | |
Male | Female** | ||
0 | 0 | Low | None |
1 | 2 | Moderate | None or oral anticoagulant |
≥2 | ≥3 | High | Oral anticoagulant |
*Patients are assigned to 1 of the 2 age categories. **Different cutoffs are used for males & females. Female sex is considered a risk modifier that adds to the CHA2DS2-VASc score only if other nonsex risk factors are present (female patients cannot have a total score of 1). MI = myocardial infarction; PAD = peripheral artery disease; TIA = transient ischemic attack. | |||
This patient with acute lower extremity pain, paresthesia, and pulselessness has acute limb ischemia. Given the patient's history of paroxysmal atrial fibrillation (AF) and irregular pulse on examination, the most likely cause is embolism of a left atrial thrombus, which might have been prevented by appropriate anticoagulation therapy.
Current guidelines recommend the use of the CHA2DS2-VASc score for thromboembolic risk assessment in patients with AF. Men with a CHA2DS2-VASc score ≥2, such as this patient (score = 3: hypertension, diabetes mellitus, age 65-74), and women with a score ≥3 are at high risk of thromboembolic events and should be managed with anticoagulation therapy. In these patients, the benefit of lowered embolization risk outweighs the risk of bleeding (eg, intracranial hemorrhage).
Apixaban is a direct oral anticoagulant (DOAC) that directly inhibits factor Xa, preventing it from cleaving prothrombin to thrombin. The DOACs, including direct thrombin inhibitors (eg, dabigatran) and direct factor Xa inhibitors (eg, apixaban, rivaroxaban, edoxaban), significantly reduce systemic embolization risk with similar or superior efficacy to warfarin but with decreased risk of severe bleeding (eg, hemorrhagic stroke) and no need for routine INR testing. In contrast, antiplatelet therapy with aspirin or a combination of aspirin and clopidogrel is significantly less effective in reducing thromboembolic risk compared with anticoagulant therapy with a DOAC or warfarin (Choices B and D).
(Choice C) Cilostazol is a phosphodiesterase inhibitor occasionally used for symptomatic management of patients with intermittent claudication, which typically presents more chronically with exertional leg pain. Although cilostazol also suppresses platelet aggregation, it is not indicated for primary thromboembolic event prevention in patients with AF.
(Choices E and F) Calcium channel blockers (eg, diltiazem) and beta blockers (eg, metoprolol) are used for heart rate control in patients with AF. Rate control helps manage symptoms and avoid hemodynamic instability from rapid ventricular response; however, unlike anticoagulation, it does not prevent thromboembolic events.
Educational objective:
An anticoagulation agent, such as a direct oral anticoagulant (eg, apixaban) or warfarin, should be used to reduce the risk of systemic thromboembolism in patients with atrial fibrillation and a high risk of thromboembolic events (ie, CHA2DS2-VASc score ≥2 for men and ≥3 for women).