What is the statistical difference a statin (HMG-CoA reductase inhibitor) brings in a patient with an intermediate Framingham risk?

Statin Therapy in Intermediate Framingham Risk Patients: Statistical Benefits

In patients with intermediate Framingham risk (7.5-19.9% 10-year ASCVD risk), moderate-intensity statin therapy reduces major cardiovascular events by approximately 44% relative risk reduction, translating to a number needed to treat (NNT) of approximately 20-30 over 5 years to prevent one major cardiovascular event. 1, 2

Absolute and Relative Risk Reductions

Primary Prevention Data:

• In the JUPITER trial, which enrolled patients with baseline coronary heart disease risk of 11.6% over 10 years (intermediate risk range), rosuvastatin 20 mg achieved a 44% relative risk reduction in major CV events (p<0.001) with an absolute risk reduction of 1.2% over a median 2-year follow-up 3
• The 5-year NNT was 20 (95% CI, 14-34) to prevent one event of myocardial infarction, stroke, revascularization, or death 2
• For the "hard" endpoint of myocardial infarction, stroke, or death alone, the 5-year NNT was 29 (95% CI, 19-56) 2

Risk Stratification Within Intermediate Risk:

• Among intermediate-risk patients (7.5-19.9% 10-year risk) with coronary artery calcium score (CACS) = 0, the observed 10-year event rate drops to 4.6%, suggesting statins may not be necessary 1
• However, intermediate-risk patients with CACS > 0 have a 10.4% observed event rate, strongly supporting statin therapy 1
• Patients with CACS ≥ 100 or in the ≥75th percentile for age/sex/race should receive statin therapy regardless of intermediate risk calculation 1

Guideline Recommendations for Intermediate Risk

ACC/AHA Guidelines:

• For adults aged 40-75 years with intermediate risk (7.5-19.9%), moderate-intensity statin therapy is recommended after clinician-patient risk discussion 1
• If maximal ASCVD risk reduction is desired and 10-year risk is ≥20%, high-intensity statin therapy is reasonable to lower LDL-C by ≥50% 1
• Clinical judgment is required to initiate statin treatment based on risk-benefit considerations and patient preferences 1

USPSTF Recommendations:

• For adults with 10-year CVD risk of 7.5% or higher, statin use is recommended with shared decision-making 1
• Evidence from RCTs supports efficacy of statin therapy for patients whose 10-year risk is 5% or higher 1

Specific Event Reductions

Individual Cardiovascular Outcomes:

• Myocardial infarction: Rosuvastatin significantly reduced fatal and nonfatal MI (68 events in placebo vs. 31 events in rosuvastatin group) 3
• Stroke: Significant reduction in fatal and nonfatal stroke (64 events in placebo vs. 33 events in rosuvastatin group) 3
• Revascularization procedures: Significant reduction in arterial revascularization 3
• No significant difference in CV death or hospitalizations for unstable angina as isolated endpoints 3

NNT Comparisons Across Risk Levels

Framingham Risk Score Stratification:

• FRS ≥5%: 5-year NNT = 525 4
• FRS 5-10%: More favorable NNT in lower intermediate range 2
• FRS 10-20%: 5-year NNT approximately 20-30 2
• FRS >20% (high risk): 5-year NNT = 14-20 2

Age-Specific Considerations:

• Ages 45-54: 10-year ASCVD rate 3.8% with CACS considered 1
• Ages 55-64: 10-year ASCVD rate 6.5% with CACS considered 1
• Ages 65-74: 10-year ASCVD rate 8.3% with CACS considered 1
• For intermediate-risk patients >55 years with CACS 1-99, 5-year NNT = 21 1

Clinical Decision-Making Algorithm

Three-Tiered Approach for Intermediate Risk (7.5-19.9%): 1

1. Calculate 10-year ASCVD risk using Pooled Cohort Equations 1

2. Assess risk-enhancing factors: 1

   • Family history of premature ASCVD
   • Persistently elevated LDL-C ≥160 mg/dL
   • Metabolic syndrome
   • Chronic kidney disease
   • Chronic inflammatory disorders
   • High-sensitivity CRP ≥2.0 mg/L
   • Ankle-brachial index <0.9
   • Lipoprotein(a) >50 mg/dL

3. Consider CACS if decision uncertain: 1

   • CACS = 0: Withhold or defer statins (10-year event rate 1.5-4.6%), especially if no smoking or family history of premature CAD 1
   • CACS 1-99: Favor moderate-intensity statin, especially age >55 years 1
   • CACS ≥100 or ≥75th percentile: Initiate moderate-to-high intensity statin 1

Comparative Effectiveness

Statin Intensity Matters:

• High-intensity statins (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) provide greater LDL-C reduction (≥50%) and greater ASCVD risk reduction compared to moderate-intensity regimens 1, 3
• The magnitude of percent LDL-C reduction achieved determines benefit 1
• Rosuvastatin 20 mg provides superior LDL-C lowering compared to atorvastatin 20 mg (-52% vs. -43%) 3

Common Pitfalls

Avoid These Errors:

• Do not automatically prescribe statins at 7.5% threshold without risk discussion and consideration of risk-enhancing factors 1
• Do not ignore CACS = 0 in intermediate-risk patients, as this reclassifies >50% to low risk, avoiding unnecessary treatment 1
• Do not use statins in intermediate-risk patients with CACS = 0 unless they are active smokers, have diabetes, or strong family history of premature CAD 1
• Do not fail to reassess CACS = 0 patients in 3-5 years, as the "warranty period" varies by age and risk factors 1

Cost-Effectiveness Considerations

• CAC testing is cost-effective in intermediate-risk patients for guiding statin decisions 1
• Treat-all strategies with generic statins appear cost-effective, but CAC testing allows for shared decision-making without adverse outcomes or increased costs 1
• In intermediate-risk patients with CACS >100, the NNT to prevent one ASCVD event is <30, making treatment highly cost-effective 1