What alternative therapies are recommended for patients with atherosclerosis?

Alternative Therapies for Atherosclerosis Management

For patients with atherosclerosis, comprehensive risk reduction through lifestyle modifications and pharmacological therapies beyond statins should be implemented, including antiplatelet therapy, combination lipid-lowering approaches, and targeted interventions for specific risk factors.

Pharmacological Alternatives to Statins

Lipid-Lowering Alternatives

• For patients who cannot achieve LDL-C goals with statins alone or who experience statin intolerance, ezetimibe should be added as a primary alternative therapy 1
• For very high-risk patients who don't achieve their LDL-C goal on maximum tolerated statin and ezetimibe, PCSK9 inhibitors are recommended 1, 2
• Bempedoic acid (alone or in fixed-dose combination with ezetimibe) can be considered for patients with statin intolerance, though availability varies by country 1
• For patients with statin-associated muscle symptoms (SAMS), a lower dose statin plus ezetimibe combination may provide similar LDL-C reduction with fewer side effects 2

Statin Intolerance Management

• Temporarily discontinue the statin to establish causality between the medication and muscle symptoms 2
• If symptoms resolve, restart with a lower dose of the same statin or switch to a different statin at a low dose with gradual titration 2
• Evaluate for conditions that might increase risk for muscle symptoms, including hypothyroidism, reduced renal or hepatic function, vitamin D deficiency, or primary muscle diseases 2

Antiplatelet and Antithrombotic Therapy

• Aspirin 75-162 mg daily is recommended for all patients with coronary artery disease unless contraindicated 1
• Clopidogrel 75 mg daily is recommended as an alternative for patients who are intolerant of or allergic to aspirin 1
• For patients with symptomatic peripheral arterial disease, antiplatelet therapy with aspirin (75-325 mg daily) or clopidogrel (75 mg daily) should be initiated 1
• In patients with extracranial carotid or vertebral atherosclerosis who have had ischemic stroke or TIA, treatment options include aspirin alone, clopidogrel alone, or the combination of aspirin plus extended-release dipyridamole 1

Comprehensive Risk Factor Management

Blood Pressure Control

• All patients should be counseled regarding lifestyle modifications for blood pressure control: weight management, increased physical activity, alcohol moderation, sodium reduction, and increased consumption of fresh fruits, vegetables, and low-fat dairy products 1
• Patients with blood pressure ≥140/90 mm Hg should be treated with antihypertensive medications, starting with beta-blockers and/or ACE inhibitors 1

Lifestyle Modifications

• Physical activity: 30-60 minutes of moderate-intensity aerobic activity at least 5 days and preferably 7 days per week 1
• Dietary modifications: reduced intake of saturated fats (to <7% of total calories), trans fatty acids (to <1% of total calories), and cholesterol (to <200 mg/day) 1
• Weight management: maintain/achieve a body mass index between 18.5 and 24.9 kg/m² and appropriate waist circumference (<35 inches for women, <40 inches for men) 1

Additional Therapeutic Options

• Omega-3 fatty acids from fish or fish oil capsules (1 g/day) may be reasonable for cardiovascular disease risk reduction 1
• For patients with elevated triglycerides (≥200 mg/dL) who continue to have elevated non-HDL-C while on adequate statin therapy, niacin or fibrate therapy may be reasonable 1

Management of Comorbidities

• ACE inhibitors (or ARBs) are recommended for patients with heart failure, hypertension, or diabetes 1
• For patients with diabetes, comprehensive risk factor management is essential, with consideration of glycemic targets appropriate to the individual's overall health status 1
• For patients with multiple risk factors or diffuse atherosclerosis, a more aggressive approach to risk factor modification is warranted 1, 3

Revascularization Considerations

• For patients with symptomatic carotid or vertebral artery disease, revascularization options include percutaneous angioplasty and stenting, direct arterial reconstruction, or extra-anatomic bypass surgery 1
• Myocardial revascularization is recommended when angina persists despite treatment with antianginal drugs 1

Important Considerations and Pitfalls

• Do not permanently discontinue lipid-lowering therapy without establishing causality for adverse effects, as many patients with initial symptoms can tolerate a lower dose or different agent 2
• Recognize that patients with diffuse atherosclerosis (involvement of multiple vascular beds) have higher risk and may require more intensive therapy 3, 4
• Initiation of combination lipid-lowering therapy (double or triple therapy) immediately during hospitalization or at the first visit may be beneficial for highest-risk patients to improve goal achievement and reduce cardiovascular events 1