What is the risk of myocardial infarction (MI) in a patient with abnormal rest/stress Single Photon Emission Computed Tomography (SPECT) myocardial perfusion images, ischemia, and infarction, taking Brilinta (ticagrelor) 90 mg, Lisinopril (angiotensin-converting enzyme inhibitor) 2.5 mg, and Atorvastatin (lipitor) 40 mg, with mildly reduced left ventricle function and a post-stress ejection fraction of 49%?

Risk Assessment and Management for Patient with Abnormal SPECT Findings

This patient is at high risk for future myocardial infarction and requires immediate intensification of medical therapy, particularly addition of a beta-blocker and consideration of coronary angiography given the combination of reversible ischemia, prior infarction, and reduced ejection fraction.

Current Risk Stratification

Nuclear Imaging Findings Indicate High-Risk Features

• The presence of moderate reversible ischemia in the apex combined with a fixed severe defect in the basal inferolateral wall indicates both active ischemia and prior infarction, placing this patient in a high-risk category 1.

• The post-stress ejection fraction of 49% represents mildly reduced left ventricular function, which is a critical prognostic indicator. Patients with LVEF <50% have significantly elevated cardiovascular risk 1.

• Patients with moderate to severe perfusion abnormalities (such as this patient's medium-sized severe fixed defect and small moderate reversible defect) have annual cardiovascular death or MI rates of 5% or higher, representing a 6- to 10-fold higher risk than patients with normal results 1.

• The moderately hypokinetic regional wall abnormality in the basal inferolateral wall further confirms prior myocardial damage and ongoing ventricular dysfunction 1.

Critical Medication Gaps

Beta-Blocker Therapy is Urgently Needed

The most significant gap in this patient's current regimen is the absence of beta-blocker therapy.

• Beta-blockers must be started and continued indefinitely in all patients who have had myocardial infarction or left ventricular dysfunction, unless contraindicated 1.

• Beta-blockers reduce mortality and reinfarction by 20-25% in patients who have recovered from acute myocardial infarction 1.

• Given this patient's LVEF of 49% (below normal threshold of >60%) and evidence of prior infarction, beta-blocker therapy carries a Class I, Level A recommendation 1, 2.

• Specific beta-blockers with proven mortality benefit include carvedilol, metoprolol succinate, and bisoprolol 2.

ACE Inhibitor Dose is Suboptimal

• The current lisinopril dose of 2.5 mg is inadequate for a patient with reduced LVEF and prior infarction 1.

• ACE inhibitors are recommended to be started and continued indefinitely in all patients with LVEF <40%, and should be strongly considered in patients with LVEF between 40-50% 1.

• The GISSI-3 trial demonstrated that lisinopril reduced mortality and left ventricular dysfunction in post-MI patients, with typical therapeutic doses ranging from 5-10 mg daily 3, 4.

• This patient's dose should be uptitrated to at least 10 mg daily, monitoring for hypotension and renal function 3.

Aldosterone Antagonist Should Be Added

• Aldosterone blockade is recommended (Class I, Level A) in post-MI patients with LVEF <40% who are already receiving therapeutic doses of an ACE inhibitor and beta-blocker 1.

• While this patient's LVEF is 49%, the presence of prior infarction, regional wall motion abnormalities, and ongoing ischemia makes aldosterone antagonist therapy reasonable to consider, particularly once beta-blocker therapy is initiated 1.

Antiplatelet Therapy Assessment

The patient is currently on Brilinta (ticagrelor) 90 mg twice daily, which is appropriate but requires context:

• If this patient had a recent acute coronary syndrome or PCI with stent placement, ticagrelor 90 mg twice daily with aspirin is appropriate for up to 12 months 1.

• For long-term secondary prevention beyond 12 months after MI, ticagrelor 60 mg twice daily (not 90 mg) plus aspirin has been shown to reduce major adverse cardiovascular events 1, 5, 6.

• The PEGASUS-TIMI 54 trial demonstrated that ticagrelor 60 mg twice daily reduced MACE with better tolerability than the 90 mg dose in patients 1-3 years post-MI 1, 5.

• If the patient is more than 12 months post-event, consider switching from ticagrelor 90 mg to 60 mg twice daily to optimize the benefit-risk ratio 1.

Statin Therapy is Adequate

• Atorvastatin 40 mg is appropriate high-intensity statin therapy 1, 7.

• The goal LDL-C should be <70 mg/dL (1.8 mmol/L) or at least a 50% reduction from baseline 1.

• Atorvastatin has demonstrated significant reduction in cardiovascular events in post-MI patients and those with established coronary disease 7, 8.

Quantifying MI Risk

Short-Term Risk (1 Year)

Based on the nuclear imaging findings and current medical therapy gaps, this patient's annual risk of MI or cardiovascular death is approximately 5-10% 1.

• The presence of reversible ischemia indicates ongoing risk for acute coronary events 1.
• The fixed defect confirms prior infarction, which independently increases recurrent event risk 1.
• The reduced LVEF of 49% further elevates risk 1.

Risk Reduction with Optimal Medical Therapy

With addition of beta-blocker therapy alone, mortality and reinfarction risk can be reduced by 20-25% 1.

With optimization of ACE inhibitor dosing, additional mortality reduction of 19-27% can be achieved 1, 3, 4.

The combination of optimal medical therapy (beta-blocker, ACE inhibitor at therapeutic dose, high-intensity statin, and appropriate antiplatelet therapy) could reduce this patient's absolute risk by approximately 40-50%, bringing annual event rates closer to 2.5-5% 1.

Immediate Management Recommendations

Coronary Angiography Should Be Strongly Considered

• The presence of moderate reversible ischemia involving the apex suggests a significant coronary lesion, likely in the left anterior descending artery 1.

• Patients with reversible ischemia involving ≥10% of the left ventricle are at high risk and warrant consideration for coronary angiography to assess for revascularization 1.

• While the COURAGE trial showed no mortality benefit from routine revascularization in stable CAD, patients with high-risk features (reduced LVEF, extensive ischemia) may benefit from revascularization 1.

Medication Optimization Algorithm

1. Immediately initiate beta-blocker therapy (carvedilol, metoprolol succinate, or bisoprolol), starting at low dose and titrating to target or maximum tolerated dose 1, 2.

2. Uptitrate lisinopril from 2.5 mg to 10 mg daily, monitoring blood pressure and renal function 1, 3.

3. Verify timing of last acute coronary event or PCI:

   • If <12 months: continue ticagrelor 90 mg twice daily with aspirin 1
   • If >12 months and high ischemic risk: consider ticagrelor 60 mg twice daily with aspirin 1, 5

4. Once beta-blocker and ACE inhibitor are at therapeutic doses, consider adding aldosterone antagonist (spironolactone or eplerenone) if no contraindications 1.

5. Ensure LDL-C is at goal (<70 mg/dL); if not, consider adding ezetimibe to atorvastatin 40 mg 1.

Common Pitfalls to Avoid

• Do not delay beta-blocker initiation - this is the most critical missing element in this patient's regimen 1, 2.

• Do not assume the current ACE inhibitor dose is adequate - 2.5 mg lisinopril is a starting dose, not a therapeutic dose for secondary prevention 1, 3.

• Do not continue ticagrelor 90 mg indefinitely - if beyond 12 months post-event, the 60 mg dose has better evidence for long-term use 1.

• Do not ignore the reversible ischemia - this requires either intensification of medical therapy or consideration of revascularization 1.

• Monitor for hypotension when initiating beta-blocker in a patient already on ACE inhibitor - start with low doses and titrate carefully 1.