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Flashcards in WHI CEE PM Hyst Deck (11)
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1

Aims

To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in US

2

Study Design

Randomised, double-blind, placebo controlled disease prevention trial

3

Participants

  • 40 US clinical centres beginning in 1993
  • 10,739 postmenopausal women, aged 50-79 years, with prior hysterectomy (23% of minority race/ethnicity)

4

Inclusion Criteria

Women 50-79 years at initial screening, had undergone hysterectomy, and likely to reside in area for 3 years

5

Exclusion Criteria

  • Competing risks: any medical condition likely to be associated with a predicted survival <3 years 
  • Safety: prior breast cancer, other prior cancer within last 10 years except nonmelanoma skin cancer
  • Adherence & retention concerns: alcoholism, dementia, transportation problems
  • Clinical judgment of participant’s health care practitioner to continue HRT in symptomatic or osteoporotic women

6

Intervention

Randomly assigned to receive either 0.625mg/d of conjugated equine estrogen (CEE) or placebo

7

Primary end-points

  • CHD incidence (nonfatal myocardial infarction or CHD death)
  • Invasive breast cancer incidence

8

Secondary end-points

A global index of risks and benefits, including the primary outcomes plus stroke, PE, colorectal cancer, hip fracture, death from other causes

9

Summary of results

  • In Feb 2004, after reviewing data through 30/11/03, NIH decided to end the intervention phase of trial early
  • Estimated hazard ratios for CEE vs placebo
    • Decreased risk: Hip fracture 0.61 (sig), CHD 0.91, Breast cancer 0.77
    • Increased risk: Stroke 1.39 (sig), PE 1.34, Colorectal cancer 1.08
  • Total CHD 1.12, total cancer 0.93, total fractures 0.70, total mortality 1.04
  • Absolute excess risk of 12 additional strokes per 10,000 person-years
  • Absolute risk reduction of 6 fewer hip fractures per 10,000 person-years
  • Estimated excess risk for all monitored events in global index was nonsignificant 2 events per 10,000 person-years

10

Limitations

  • Only oral preparation -> results do not apply to other formations, doses or routes of administration
  • High rates of discontinuation
    • Lack of adherence -> diluted CEE effects, both +ve and –ve
  • Lower than anticipated event rates for some outcomes
  • Trial was stopped early therefore strong associations for breast cancer cannot be shown

11

Conclusion

  • Use of CEE increases risk of stroke, decreases risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years
  • Possible reduction in breast cancer risk requires further investigation
  • Burden of incidence disease events were equivalent in CEE and placebo groups (à no overall benefit)
  • Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women