What are the strategies for secondary prevention in cerebrovascular accident (CVA) or stroke?

From the Guidelines

Secondary prevention in stroke should prioritize a comprehensive approach including antiplatelet therapy, anticoagulation for atrial fibrillation, blood pressure control, lipid management, lifestyle modifications, and management of diabetes and carotid stenosis, as recommended by the most recent guidelines 1. The cornerstone of secondary prevention includes antiplatelet therapy, typically starting with aspirin 81-325 mg daily, clopidogrel 75 mg daily, or a combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily.

• For patients with atrial fibrillation, anticoagulation with warfarin (target INR 2-3) or direct oral anticoagulants like apixaban, rivaroxaban, or dabigatran is recommended.
• Blood pressure control is crucial, aiming for targets below 130/80 mmHg using medications such as ACE inhibitors, ARBs, calcium channel blockers, or thiazide diuretics.
• Lipid management with high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) is indicated regardless of baseline cholesterol levels.
• Lifestyle modifications are essential, including:
  • Smoking cessation
  • Limiting alcohol consumption
  • Maintaining a Mediterranean or DASH diet
  • Regular physical activity, as emphasized in the 2014 statement from the American Heart Association/American Stroke Association 1
  • Weight management
• For patients with significant carotid stenosis (>70%), carotid endarterectomy or stenting should be considered.
• Diabetes management with a target HbA1c <7% helps reduce recurrent stroke risk. These interventions work by addressing the underlying mechanisms of stroke, including thrombosis, atherosclerosis, and hypertension, thereby reducing the risk of subsequent cerebrovascular events by up to 80% when implemented comprehensively, as supported by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

From the FDA Drug Label

The evidence for the efficacy and safety of XARELTO for the reduction in the risk of stroke, myocardial infarction, or cardiovascular death in patients with coronary artery disease (CAD) or peripheral artery disease (PAD) was derived from the double-blind, placebo-controlled Cardiovascular OutcoMes for People using Anticoagulation StrategieS trial (COMPASS) [NCT10776424].

A total of 27,395 patients were evenly randomized to rivaroxaban 2.5 mg orally twice daily plus aspirin 100 mg once daily, rivaroxaban 5 mg orally twice daily alone, or aspirin 100 mg once daily alone.

Relative to placebo, XARELTO reduced the rate of the primary composite outcome of stroke, myocardial infarction or cardiovascular death: HR 0.76 (95% CI: 0.66,0.86; p=0.00004).

In the COMPASS CAD population, the benefit was observed early with a constant treatment effect over the entire treatment period.

The strategies for secondary prevention in cerebrovascular accident (CVA) or stroke include:

• Anticoagulation therapy: Rivaroxaban 2.5 mg orally twice daily plus aspirin 100 mg once daily has been shown to reduce the risk of stroke, myocardial infarction, or cardiovascular death in patients with CAD or PAD 2.
• Aspirin therapy: Aspirin 100 mg once daily is used as background therapy in combination with rivaroxaban for secondary prevention of stroke, myocardial infarction, or cardiovascular death 2.
• Reduction of cardiovascular risk factors: Managing cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia is crucial for secondary prevention of stroke 2.

Note: The FDA drug label provides evidence for the efficacy and safety of rivaroxaban in reducing the risk of stroke, myocardial infarction, or cardiovascular death in patients with CAD or PAD, but it does not provide a comprehensive list of strategies for secondary prevention in CVA or stroke.

From the Research

Strategies for Secondary Prevention in Cerebrovascular Accident (CVA) or Stroke

The following strategies are recommended for secondary prevention in cerebrovascular accident (CVA) or stroke:

• Lifestyle modification to improve cardiovascular health, along with strict control of blood pressure, glucose, and lipids 3
• Antiplatelet therapy, such as aspirin, clopidogrel, and combined aspirin + extended-release dipyridamole, for the secondary prevention of noncardioembolic ischemic stroke 3, 4, 5, 6
• Anticoagulation therapy, such as adjusted-dose warfarin, for patients with cardioembolic stroke or nonvalvular atrial fibrillation 4
• Management of modifiable risk factors, such as obesity, smoking, and excessive alcohol consumption 3
• Carotid endarterectomy or anticoagulation for atrial fibrillation, as specific interventions for secondary prevention 7
• Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor for 21-30 days, followed by single-antiplatelet therapy (SAPT), for patients with minor acute noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) 5

Antiplatelet Therapy

Antiplatelet therapy is a crucial component of secondary stroke prevention, with the following options:

• Aspirin monotherapy 4, 5, 6
• Combined aspirin and extended-release dipyridamole 3, 4, 5, 6
• Clopidogrel monotherapy 3, 4, 5, 6
• Ticagrelor, a new antiplatelet drug with promising results, but requiring further randomized clinical trials to assess safety and efficacy 5, 6

Risk Factor Management

Management of modifiable risk factors is essential for secondary stroke prevention, including:

• Hypertension control through antihypertensive treatment 4
• Dyslipidemia management with HMG-CoA reductase inhibitor (statin) therapy 4
• Diabetes mellitus control, with treatment options such as pioglitazone 4
• Lifestyle modifications, including smoking cessation, weight management, and reduction of excessive alcohol consumption 3, 7