What is the number needed to treat (NNT) with statins, such as atorvastatin (lipitor) or simvastatin (zocor), to prevent one major vascular event, such as heart attack or stroke?

Number Needed to Treat with Statins to Prevent Heart Attack or Stroke

Based on the most recent evidence, the number needed to treat (NNT) with statins to prevent one first recurrent stroke over 1 year is 258, and to prevent one nonfatal myocardial infarction, the NNT is 288. 1

NNT Values from Major Statin Trials

• The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial demonstrated that for patients with a history of stroke or TIA, treating 258 patients with atorvastatin 80mg daily for one year would prevent one recurrent stroke 1
• In the same population, treating 288 patients with atorvastatin for one year would prevent one nonfatal myocardial infarction 1
• The 5-year absolute risk reduction for major cardiovascular events was 3.5% in the SPARCL trial, with a hazard ratio of 0.80 (95% CI, 0.69 to 0.92; p=0.002) 1

Factors Affecting NNT with Statins

• Baseline Risk Profile: The NNT varies significantly based on patient risk factors:

  • For intermediate-risk patients with coronary artery calcium score (CACS) = 0, the NNT to prevent one ASCVD event is 64 1
  • For patients with CACS > 100, the NNT decreases to 28, indicating greater benefit 1

• LDL-C Reduction: Greater LDL-C reduction correlates with improved outcomes:

  • Patients achieving ≥50% reduction in LDL-C had a 35% reduction in combined risk of fatal and nonfatal stroke 1
  • Achieving an LDL-C level of <70 mg/dL was associated with a 28% reduction in risk of stroke without increasing hemorrhagic stroke risk 1

Statin Efficacy in Different Patient Populations

• Secondary Prevention: Statins provide substantial benefit for patients with established cardiovascular disease:

  • In patients with previous stroke or TIA, atorvastatin 80mg daily reduced the overall incidence of strokes by 16% compared to placebo over 4.9 years 1, 2
  • The reduction in ischemic strokes was 37% (HR, 0.63; 95% CI, 0.49 to 0.81) in patients achieving significant LDL-C reduction 1

• Primary Prevention: For patients without established cardiovascular disease:

  • Meta-analyses show that statin therapy provides high levels of protection for all-cause mortality and nonhemorrhagic strokes 3
  • The benefit appears to be independent of the patient's initial cholesterol levels 4

Safety Considerations

• Hemorrhagic Stroke Risk: There was a slightly higher incidence of hemorrhagic stroke in the atorvastatin treatment arm in SPARCL (2.3% vs 1.4% for placebo) 1

• Risk Factors for Hemorrhagic Stroke: Increased risk was associated with:

  • Previous hemorrhagic stroke (HR, 5.65; 95% CI, 2.82 to 11.30) 1
  • Male sex (HR, 1.79,95% CI, 1.13 to 2.84) 1
  • Advanced age (10-year increments; HR, 1.42; 95% CI, 1.16 to 1.74) 1
  • Stage 2 hypertension 1

• Other Side Effects: Statin therapy was generally well tolerated in clinical trials:

  • Elevated liver enzymes were more common with atorvastatin (2.2% vs 0.5% with placebo) 1
  • No significant differences in myalgia (5.5% vs 6.0%), myopathy (0.3% vs 0.3%), or rhabdomyolysis (0.1% vs 0.1%) between atorvastatin and placebo 1

Clinical Recommendations

• For Secondary Prevention: Statin therapy with intensive lipid-lowering effects is recommended for patients with ischemic stroke or TIA who have evidence of atherosclerosis, an LDL-C level >100 mg/dL, and who are without known coronary heart disease 1

• Target LDL-C Levels: For patients with atherosclerotic ischemic stroke or TIA, it is reasonable to target:

  • A reduction of at least 50% in LDL-C or
  • A target LDL-C level of <70 mg/dL to obtain maximum benefit 1, 5

• Monitoring: Regular follow-up is essential:

  • Check lipid levels 4-12 weeks after initiating therapy to assess efficacy and adherence 5
  • Continue monitoring every 3-12 months thereafter 5