What are the current treatment recommendations for patients with cardiovascular disease based on recent trials?

Current Treatment Recommendations for Cardiovascular Disease Based on Recent Trials

All patients with cardiovascular disease should receive comprehensive medical therapy including statins (with combination therapy if needed to reach targets), antiplatelet agents, ACE inhibitors or ARBs (especially with comorbidities), and beta-blockers, alongside aggressive lifestyle modification and multidisciplinary management. 1

Core Pharmacological Strategy

Lipid-Lowering Therapy (Highest Priority)

Statins are mandatory for all patients with cardiovascular disease, regardless of baseline cholesterol levels. 1, 2

• Target LDL-C <70 mg/dL (1.8 mmol/L) for all patients with established coronary artery disease or equivalent risk 1, 3
• Start with high-intensity statin therapy (atorvastatin 80 mg daily) for patients at very high or extremely high risk 1, 4
• If LDL-C goals are not achieved with maximum tolerated statin dose, add ezetimibe 1, 2
• For very high-risk patients not reaching goals on statin plus ezetimibe, add a PCSK9 inhibitor 1
• The concept of "lower is better" for LDL-C is strongly supported, with evidence showing benefit even at LDL-C levels as low as 73 mg/dL 3, 5

Antiplatelet Therapy

Aspirin 75-100 mg daily is recommended for all patients with previous MI or revascularization 1, 2

• Following coronary stenting, dual antiplatelet therapy (aspirin plus clopidogrel 75 mg daily) is required for 6 months, unless shorter duration (1-3 months) is indicated due to life-threatening bleeding risk 1
• Clopidogrel 75 mg daily is recommended as an alternative to aspirin in patients with aspirin intolerance 1
• Add a proton pump inhibitor for patients at high risk of gastrointestinal bleeding receiving aspirin monotherapy, dual antiplatelet therapy, or oral anticoagulation 1

ACE Inhibitors or ARBs

ACE inhibitors (or ARBs if ACE inhibitors not tolerated) are recommended in the presence of heart failure, hypertension, diabetes, or left ventricular dysfunction following MI 1, 2, 6

• ACE inhibitors reduce cardiovascular death, MI, and cardiac arrest by approximately 20% in patients with coronary artery disease 6
• Valsartan 160 mg twice daily represents an alternative to ACE inhibitors in patients who do not tolerate ACE inhibitors and have clinical signs of heart failure and/or ejection fraction ≤40% 1
• ARBs are recommended as alternatives in patients who do not tolerate ACE inhibition 1

Beta-Blockers

Beta-blockers are essential components of treatment for both angina relief and reduction of morbidity and mortality in heart failure 1, 2, 6

• Beta-blockers should be continued for at least 2 years after MI 1
• First-line treatment for controlling heart rate and symptoms in chronic coronary syndromes 1

Mineralocorticoid Receptor Antagonists

MRAs are recommended for patients who remain symptomatic despite adequate treatment with ACE inhibitor and beta-blocker 1, 2, 6

• Eplerenone in post-STEMI patients with ejection fraction ≤40% and heart failure or diabetes showed 15% relative reduction in total mortality 1
• Critical monitoring required: ensure creatinine <2.5 mg/dL in men and <2.0 mg/dL in women, and potassium <5.0 mEq/L before initiation 1
• Routine serum potassium monitoring is warranted, particularly when combined with ACE inhibitors or ARBs 1, 6

Special Populations and Conditions

Patients with Atrial Fibrillation

When oral anticoagulation is initiated in a patient with AF eligible for a NOAC, a NOAC is recommended in preference to a VKA 1

• Long-term OAC therapy recommended in patients with AF and CHA₂DS₂-VASc score ≥2 in males and ≥3 in females 1
• In post-PCI patients with AF, use NOAC (apixaban 5 mg b.i.d., dabigatran 150 mg b.i.d., edoxaban 60 mg o.d., or rivaroxaban 20 mg o.d.) in preference to VKA in combination with antiplatelet therapy 1
• Ticagrelor or prasugrel are NOT recommended as part of triple antithrombotic therapy with aspirin and an OAC 1

Patients with Diabetes

Glucometabolic disturbances should be actively searched for, with target HbA1c levels ≤6.5% 1

• Perform glucose tolerance test before or shortly after discharge in patients with MI 1
• ACE inhibitors or ARBs are particularly important in diabetic patients with cardiovascular disease 1
• In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, incorporate an agent proven to reduce major adverse cardiovascular events (empagliflozin or liraglutide) after metformin 1

Patients with Heart Failure

Diuretic therapy is recommended in symptomatic patients with signs of pulmonary or systemic congestion 1, 2, 6

• Angiotensin receptor-neprilysin inhibitor recommended for patients with persistent symptoms despite optimal medical therapy 1, 6
• Implantable cardioverter-defibrillator recommended for patients with symptomatic HF and LVEF <35% to reduce sudden death and all-cause mortality 1
• CRT recommended for symptomatic patients in sinus rhythm with QRS duration ≥150 ms and LBBB morphology, and LVEF <35% despite optimal medical therapy 1

Lifestyle Modifications and Non-Pharmacological Management

Comprehensive lifestyle modification is mandatory and includes smoking cessation, dietary counseling, structured physical activity, and weight management 1, 2, 7

• Exercise-based cardiac rehabilitation is recommended as an effective means to achieve healthy lifestyle and manage risk factors 1, 2, 7
• Multidisciplinary team involvement (cardiologists, primary care physicians, nurses, dieticians, physiotherapists, psychologists, pharmacists) is recommended 1, 2, 7
• Psychological interventions are recommended to improve symptoms of depression 1, 2, 7
• Annual influenza vaccination is recommended, especially in elderly patients 1, 7

Blood Pressure and Additional Risk Factor Control

Target blood pressure <130/80 mmHg in patients with stroke, MI, or renal disease 1

• Comprehensive risk profiling and management of major comorbidities including hypertension, hyperlipidemia, diabetes, anemia, and obesity is required 1, 7

Revascularization Considerations

Myocardial revascularization is recommended when angina persists despite optimal antianginal drug treatment 1, 6

• In symptomatic patients with high-risk clinical profile, invasive coronary angiography complemented by FFR is recommended for cardiovascular risk stratification 1
• Coronary CTA is NOT recommended as a routine follow-up test for patients with established CAD 1

Critical Clinical Pitfalls to Avoid

• Do not use ticagrelor or prasugrel as part of triple antithrombotic therapy with aspirin and oral anticoagulation 1
• Avoid nitrates in patients with hypertrophic obstructive cardiomyopathy or those taking phosphodiesterase inhibitors 1, 7
• Monitor renal function and potassium levels when initiating ACE inhibitors, especially in patients with pre-existing renal impairment 6
• When adding MRAs, closely monitor potassium levels, particularly when combined with ACE inhibitors or ARBs 1, 6
• Review treatment response at 2-4 weeks after drug initiation to ensure adequate symptom control and medication tolerance 7
• High-dose statin therapy (atorvastatin 80 mg) is safe and well-tolerated, with muscle-related adverse events not more frequent than standard doses 8

Evidence from High-Dose Statin Trials

High-dose atorvastatin 80 mg daily has demonstrated superior outcomes compared to standard-dose therapy across multiple clinical scenarios 4, 9, 8, 5, 10

• In acute coronary syndromes, high-dose atorvastatin reduces cardiovascular morbidity after the first 4 months following the event 3, 9
• In stable coronary artery disease, atorvastatin 80 mg significantly reduced non-fatal MI (22% reduction) and stroke (25% reduction) compared to atorvastatin 10 mg 4
• In stroke/TIA patients, atorvastatin 80 mg reduced overall stroke incidence (5-year absolute risk reduction 2.2%) and major cardiovascular events (3.5% absolute risk reduction) 5
• High-dose atorvastatin can halt and, in some cases, reverse atherosclerotic progression 9, 10