What are the management strategies for a patient with a high MACE (Major Adverse Cardiovascular Events) score?

Management of Patients with High MACE Score

Patients with high MACE scores require immediate implementation of comprehensive cardiovascular risk reduction therapy centered on high-intensity statin therapy, antiplatelet agents, blood pressure control to <130/80 mmHg, and in diabetics with established atherosclerotic disease, addition of SGLT2 inhibitors or GLP-1 receptor agonists regardless of glycemic control. 1

Risk Stratification Framework

High-risk patients are defined as those with:

• GRACE score >140 in acute coronary syndrome presentations 2
• HEART score ≥7 (associated with >26% 30-day MACE rate) 2, 3
• Revised Cardiac Risk Index (RCRI) ≥3 in perioperative settings 4
• Established atherosclerotic disease in multiple vascular beds 5

The 2024 ACC/AHA guidelines define elevated perioperative risk as ≥1% predicted MACE, though patients with RCRI ≥3 carry substantially higher risk requiring aggressive intervention 6, 4. In acute coronary syndrome, GRACE demonstrates superior discriminative ability (C-statistic 0.83) compared to physician judgment alone 2.

Core Pharmacologic Interventions

Lipid Management

• Initiate high-intensity statin therapy immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily), which reduces MACE by approximately 15% compared to moderate-intensity statins 1
• Add ezetimibe 10 mg daily if LDL-C remains ≥70 mg/dL on maximally tolerated statin, providing additional MACE reduction over 6 years 1
• Consider PCSK9 inhibitors (evolocumab 140 mg every 2 weeks or alirocumab 75-150 mg every 2 weeks) if LDL-C ≥70 mg/dL despite statin plus ezetimibe, achieving 15% relative risk reduction in MACE over 2-3 years 1
• Target LDL-C <70 mg/dL, ideally <55 mg/dL in very high-risk patients with multiple vascular bed involvement 1

Antiplatelet Therapy

• Prescribe aspirin 75-100 mg daily for all patients with established atherosclerotic disease 1
• Clopidogrel 75 mg daily is an alternative for aspirin-intolerant patients or may be preferred in peripheral artery disease 1
• Consider dual pathway inhibition (rivaroxaban 2.5 mg twice daily plus aspirin) in high ischemic risk peripheral artery disease without high bleeding risk 1
• Do not continue dual antiplatelet therapy beyond 12 months post-ACS or 6 months post-revascularization without specific high-risk features, as bleeding risk outweighs benefit 1

Blood Pressure Control

• Target systolic BP <130 mmHg and diastolic BP <80 mmHg in all patients with atherosclerotic disease 1
• Initiate ACE inhibitors or ARBs as first-line therapy, which reduced MI, stroke, or vascular death by 25% in the HOPE trial 1

Diabetes-Specific Therapies

• In patients with type 2 diabetes and established ASCVD, add SGLT2 inhibitors or GLP-1 receptor agonists to reduce MACE by 14% independent of glucose-lowering effects 6, 1
• Specific agents with proven MACE reduction include:
  • GLP-1 receptor agonists: dulaglutide, liraglutide, injectable semaglutide 6, 1
  • SGLT2 inhibitors: empagliflozin, canagliflozin, dapagliflozin 6, 1
• For patients with established atherosclerotic CVD (prior MI, ischemic stroke, unstable angina with ECG changes, or revascularization), the level of evidence for MACE benefit is greatest for GLP-1 receptor agonists 6
• For patients with heart failure with reduced ejection fraction (EF <45%) or CKD (eGFR 30-60 mL/min/1.73m² or UACR >30 mg/g), the level of evidence for benefit is greatest for SGLT2 inhibitors 6

Revascularization Considerations

Acute Coronary Syndrome

• High-risk patients (GRACE >140 or HEART ≥7) require early invasive strategy with cardiac catheterization and potential revascularization 6, 2
• Radial artery access is preferred over femoral access, reducing all-cause death by 24% and major bleeding by 51% in ACS patients 6
• Intracoronary imaging guidance (IVUS or OCT) should be used for PCI in complex lesions, reducing target vessel failure 6

Stable Coronary Disease

• Revascularization (CABG or PCI with everolimus-eluting stents) reduces death or MI compared to medical therapy alone in patients with moderate to severe ischemia 6
• CABG demonstrates mortality benefit (HR 0.80,95% CI 0.70-0.91) compared to medical treatment in appropriate candidates 6
• Revascularization is associated with lower MACE rates when fractional flow reserve (FFR) is <0.75 in unadjusted models 6

Additional Risk Reduction Strategies

• Administer annual influenza vaccination, which reduces cardiovascular events by approximately 37% in patients with established CVD 1
• Complete SARS-CoV-2 vaccination series including boosters, as patients with cardiovascular comorbidities have higher risk for thrombotic events and death with COVID-19 infection 1
• Prescribe Mediterranean diet supplemented with extra-virgin olive oil or nuts, which significantly lowered MACE risk in high cardiovascular risk patients in the PREDIMED study 1

Perioperative Management

For patients with high perioperative risk (RCRI ≥3 or calculated MACE risk ≥1%): 6, 4

• Continue beta-blockers in patients already taking them, as they do not worsen walking capacity or limb events in PAD 1
• Implement comprehensive cardiac monitoring and consider surveillance for myocardial injury after noncardiac surgery (MINS) 4
• Assess functional capacity using Duke Activity Status Index (DASI) and B-type natriuretic peptide levels for additional risk stratification 4

Critical Pitfalls to Avoid

• Never use full-intensity oral anticoagulation monotherapy for PAD without another indication (e.g., atrial fibrillation), as it increases bleeding without reducing MACE or limb events 1
• Avoid de-escalating high-intensity statin therapy in patients tolerating treatment, even if very low LDL-C levels are achieved, as no safety concerns exist and benefit persists 1
• Do not discharge patients with HEART scores ≥7 from the emergency department without definitive evaluation, as their 30-day MACE risk exceeds 26% 2, 3
• Recognize that normal ECG does not exclude high risk in patients with suspected ACS, as approximately 10-17% of patients with normal ECGs still experience MACE 2

Monitoring and Follow-up

• Reassess lipid levels 4-12 weeks after initiating or adjusting lipid therapy, targeting LDL-C <70 mg/dL (ideally <55 mg/dL in very high-risk patients) 1
• Evaluate ischemic and bleeding risk at every follow-up visit for patients on dual pathway inhibition 1
• Monitor for bleeding complications particularly in the first 3 months of dual pathway therapy 1
• Assess clinical and functional status, medication adherence, and limb symptoms at least annually in PAD patients 1