PROSPER - Statins in the elderly

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Shepherd J, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): A randomised controlled trial. Lancet 2002;360:1623-30.

Bottom-line: In elderly patients with at least 1 additional CV risk factor or existing CVD, statin therapy reduces the risk of CV death, MI or stroke (NNT 48) over 3.2 years. 

As in other scenarios, the absolute benefit of statins depends on the underlying risk for CVD events, as well as competing causes of morbidity & mortality.

 

Patients (n=5804)

  • Included
    • Age 70-82 y
    • Total cholesterol 4.0-9.0 mmol/L
    • Plus either:
      • Existing vascular disease (cerebrovascular disease, CAD, PAD)
      • 1+ other risk factor: smoking, HTN, diabetes
  • Excluded
    • Poor cognitive function (MMSE <24)
      • Triglycerides >6.0 mmol/L
  • 23,770 screened -> 7056 entered run-in -> 5804 randomized
  • "Typical" study patient
    • Age 75 y
    • Female 52%
    • PMHx
      • Any vascular disease 43%: MI (14%), angina (26%) stroke/TIA (11%)
      • Smoker 27%
      • HTN 62%
      • Diabetes 11%
    • SBP 154/84 mm Hg
    • Lipids: Total cholesterol 5.7 mmol/L, LDL 3.8 mmol/L

Interventions

  • I: Pravastatin 40 mg PO once daily
  • C: Matching placebo

Results @ mean 3.2 years

  • LDL
    • @ baseline: 3.8 mmol/L
    • @ 3 months: Pravastatin 2.5 mmol/L (34% lower than placebo)
  • Death: Pravastatin 10.3%, placebo 10.5% (hazard ratio 0.97, 0.83-1.14)
  • Primary outcome (coronary death, non-fatal MI, fatal or non-fatal stroke): 14.1% vs 16.2% (HR 0.85, 0.74-0.97), NNT 48
    • MI: 10.1% vs 12.2%
    • Stroke: 4.7% vs 4.5%
  • Adverse events
    • New cancer: HR 1.25, 1.04-1.51
      • Note: Analyses considering all statin studies show that this likely represents a chance finding
    • Myalgia: 1.2% vs 1.1%
    • Rhabdomyolysis: 0% in both groups
  • Subgroup analyses did not demonstrate significant test for interaction for relative reduction of primary outcome comparing secondary or primary prevention (p=0.19), despite numerical differences in hazard ratios

Generalizability

  • Represents a mix of elderly/very elderly with a primary or secondary prevention indication for statin therapy
  • Run-in phase: 4-week single-blind placebo to ensure adherence to at least 75% of doses

Internal validity

  • Low risk of allocation, performance, detection and attrition bias
    • Central allocation
    • All personnel & adjudicators unaware of allocation
    • <1% withdrew consent or lost-to-follow-up
    • Intention-to-treat analysis