What is the strongest predictor of risk for cardiac death or non-fatal myocardial infarction (MI) in patients with coronary artery disease (CAD)?

From the Guidelines

The strongest predictor of risk for cardiac death or non-fatal myocardial infarction (MI) in patients with coronary artery disease (CAD) is the extent and severity of myocardial ischemia, as evidenced by studies such as 1, which demonstrated a strong relationship between the extent of ischemia and prognosis. Patients with more extensive and severe ischemia, particularly those with multiple areas of compromised blood flow, face significantly higher risks of adverse cardiac events. This risk assessment is typically determined through stress testing methods such as nuclear perfusion imaging, stress echocardiography, or cardiac MRI, which can quantify the percentage of myocardium affected by ischemia. Some key points to consider include:

• The extent of ischemia is a strong predictor of cardiac death or non-fatal MI, with patients having more than 10-12% of the myocardium affected being considered at high risk 1.
• Other important but less powerful predictors include left ventricular ejection fraction, the anatomical extent of coronary disease, history of previous MI, diabetes mellitus, chronic kidney disease, and elevated cardiac biomarkers.
• The physiological basis for this relationship stems from the fact that areas of myocardium with compromised blood flow are more vulnerable to infarction when coronary blood flow is further reduced, and larger areas of ischemia indicate more extensive coronary disease with less collateral protection, creating greater risk for significant cardiac events.
• Studies such as 1 and 1 provide additional context and support for the importance of assessing myocardial ischemia in patients with CAD, but the most recent and highest quality evidence comes from 1, which highlights the critical role of ischemia extent in predicting outcomes.

From the FDA Drug Label

The primary endpoint was the time-to-first occurrence of any of the following major cardiovascular events (MCVE): death due to CHD, non-fatal myocardial infarction, resuscitated cardiac arrest, and fatal and non-fatal stroke The mean LDL-C, TC, TG, non-HDL, and HDL cholesterol levels at 12 weeks were 73,145,128,98, and 47 mg/dL during treatment with 80 mg of atorvastatin calcium and 99,177,152,129, and 48 mg/dL during treatment with 10 mg of atorvastatin calcium. Treatment with atorvastatin calcium 80 mg/day significantly reduced the rate of MCVE (434 events in the 80 mg/day group vs. 548 events in the 10 mg/day group) with a relative risk reduction of 22%, HR 0.78,95% CI (0.69,0.89), p=0.0002

The strongest predictor of risk for cardiac death or non-fatal MI in patients with CAD is not directly stated in the provided drug labels. However, the labels do provide information on the reduction of major cardiovascular events, including non-fatal myocardial infarction and cardiac death, with atorvastatin treatment.

• Key factors associated with reduced risk include:
  • Lower LDL-C levels
  • Lower rates of major cardiovascular events
  • Reduced risk of non-fatal, non-procedure related MI
  • Reduced risk of stroke (fatal and non-fatal) 2

From the Research

Predictors of Risk for Cardiac Death or Non-Fatal MI in Patients with CAD

The strongest predictors of risk for cardiac death or non-fatal myocardial infarction (MI) in patients with coronary artery disease (CAD) can be identified through various studies.

• Age is a significant predictor, as shown in a study published in 2004, where age was found to be an independent association with the degree of CAD 3.
• Other predictors include heart failure, number of diseased coronary arteries, diabetes, previous revascularization, current smoking, female gender, previous MI, and high-density lipoprotein cholesterol levels, as identified in a 2020 study 4.
• The modified Charlson Index (MCI) and the CAD-specific index (CSI) are also powerful tools for predicting all-cause mortality in patients with established CAD, with the MCI being the strongest predictor 5.
• A meta-prediction framework that integrates unmodifiable risk factors, such as age and genetics, with modifiable risk factors, can produce actionable and personalized risk estimates for CAD 6.
• However, some studies have found that certain factors, such as angiotensin-converting enzyme inhibition, may not have a significant effect on transient ischemia in low-risk CAD patients 7.

Risk Prediction Tools

Several risk prediction tools have been developed to assess the probability of death or MI in patients with stable CAD.

• A risk score developed from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Therapy Evaluation Trial can predict the 5-year probability of death or MI, with a potential range from 0 to 15 corresponding to 5-year event rates of 5.8% to 56% 4.
• The MCI and CSI can also be used to predict all-cause mortality in patients with established CAD, with the MCI having a higher chi2 value and area under the receiver operator characteristic curve than the CSI 5.