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Oral Contraceptives and CVD Epidemiologic Effects

Oral Contraceptives and CVD Epidemiologic Effects. TMM Farley Department of Reproductive Health and Research World Health Organization Geneva. Overview. Rationale for WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception

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Oral Contraceptives and CVD Epidemiologic Effects

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  1. Oral Contraceptives and CVDEpidemiologic Effects TMM Farley Department of Reproductive Health and Research World Health Organization Geneva

  2. Overview • Rationale for WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception • Venous thromboembolism, stroke and myocardial infarction • Supplement with data from other recent studies • Overall cardiovascular risk

  3. WHO Study of Cardiovascular Disease and Steroid Hormone Contraception - 1986 • OC composition and patterns of use have changed since late 1970s • Most information refers to older products • No information available on risks in women from developing countries • “What are the cardiovascular risks associated with modern OCs used in modern ways?”

  4. WHO Study of Cardiovascular Disease and Hormonal Contraception

  5. WHO CVD Study - Design • Hospital-based case-control study • 17 countries (12 developing, 5 in Europe) • Conducted February 1989 - January 1993 • First time cases of stroke, AMI or idiopathic VTE in women aged 20-44 years • 3 controls per case, matched on age, hospital and time period • 2,242 stroke, 368 AMI, 1,143 VTE, 10,025 controls

  6. Venous Thromboembolism Adjusted odds ratio (95% CI) WHO, Lancet 1995; 346:1575

  7. Risk Factors for Idiopathic VTE • Increased relative risk with • OC use • elevated body mass index • hypertension in pregnancy • No effect on relative risk • smoking, age, hypertension • duration of OC use • previous OC use WHO, Lancet 1995; 346:1575

  8. VTE and Low Estrogen OCs Adjusted odds ratios (95% CI) WHO, Lancet 1995; 346:1575

  9. VTE and Low Estrogen OCs • Excess risk with desogestrel & gestodene compared with levonorgestrel • About 2.5  higher risk • Similar excess risk for the two products • Bias or confounding unlikely explanation • Unexpected, Unexplained, Unwelcome, Uncomfortable • “Must be confirmed by independent research”

  10. 3rd Gen vs. Levonorgestrel Overall risk ratio (95% CI) 1.9 (1.5, 2.2) Adjusted risks relative to non-users (crude risk) Lancet 1995; 346:1582, 1589, 1593; BMJ 1996; 312: 83; Contraception 1998; 57: 291

  11. Ischaemic Stroke • Major risk factors • smoking • hypertension • rheumatic heart disease • diabetes • Overall risk with OC use 2.9 (2.2 - 3.9) • No effect of past OC use or duration of use

  12. Ischaemic Stroke - smoking Pooled adjusted odds ratio (95% CI) [% controls] WHO, Lancet 1996; 348: 498

  13. Ischaemic Stroke - Hypertension Pooled adjusted odds ratio (95% CI) [% controls] WHO, Lancet 1996; 348: 498

  14. Ischaemic Stroke and Low Estrogen OCs • Kaiser, CA 1.2 (0.5, 2.6) • Washington State 1.4 (0.5, 3.8) • Denmark 1.6 (1.1, 2.4) • WHO Europe 1.4 (0.6, 3.1) Developing countries 3.4 (2.2, 3.1) • TransNational 2.8 (2.0, 3.8) RR (95% CI) compared with non-users

  15. Ischaemic Stroke and Low Estrogen OCs • With Blood Pressure check WHO Europe 1.3 (0.5, 3.5) WHO Developing 2.1 (1.1, 3.8) TransNational 2.1 (1.4, 3.1) • Without Blood Pressure check WHO Europe 1.5 (0.5, 4.6) WHO Developing 5.2 (2.9, 9.1) TransNational 4.5 (2.6, 8.0) RR (95% CI) compared with non-users

  16. Ischaemic stroke - Conclusion • Some excess risk associated with low estrogen dose OCs • Smoking and hypertension potentiate OC-associated risk • Lower risk when screened for hypertension • No evidence of difference in risk according to OC type (2nd vs. 3rd generation)

  17. Haemorrhagic Stroke • No difference according to BP checking • No impact on risk in women < 35 years • About 2  risk in women over 35 years • Higher (relative) risk among older women, smokers, women with hx of hypertension • Smoking has greater impact on risk of haemorrhagic than ischaemic stroke • Consistent with data from Kaiser, CA (Petitti, 1996)

  18. Myocardial Infarction • Major risk factors • smoking, hypertension, rheumatic heart disease, diabetes, hyperlipidaemia • Overall risk with OC use 4.9 (3.1 - 7.8) • No effect of past OC use or duration of use • Lower risks with low compared with high dose OCs

  19. AMI - Hypertension & OC use Pooled adjusted odds ratio (95% CI) [% controls] WHO, Lancet 1997; 349: 1202

  20. AMI - smoking & OC use Pooled adjusted odds ratio (95% CI) [% controls] WHO, Lancet 1997; 349: 1202

  21. AMI - Conclusion • Majority of cases (78%) occur in smokers • Lower risk with low dose OCs, in women without CV risk factors and who reported BP check (similar observations in TransNational study) • Among women with no cardiovascular risk factors who do not smoke, RR = 1.1 in women with BP check

  22. AMI and Type of OC Lancet 1997; 349: 1202; Contraception 1997; 56: 129; BMJ 1999; 318: 1579; NEJM 2001; 345: 1787

  23. Overall Cardiovascular Risk • Different risk factors for VTE and stroke or MI • Age distribution of VTE, stroke and MI cases very different over 15 - 44 age range • Any reduction in MI risk for third generation OC users more important for older women and smokers

  24. Observed CVD Incidence Oxford VTE Incidence (per 100 000 wyrs) Haemorrhagic stroke AMI Ischaemic stroke Age group (years) J Epidemiol Comm Health 1998; 52: 775

  25. 20-24y 20-24y 30-34y 30-34y 40-44y 40-44y CVD Incidence - Non-smoker Non-OC user OC user Events per 106 wyrs

  26. 20-24y 20-24y 30-34y 30-34y 40-44y 40-44y CVD Mortality - Non-smoker Non-OC user OC user Deaths per 106 wyrs

  27. OCs and CVD • OCs most widely studied pharmacologic agent • In young women without cardiovascular risk factors, OCs are safe • Excess risk seen in older women, smokers and those with pre-existing risk factors • Risk-benefit of 2nd vs. 3rd generation OCs • VTE risk more important in younger women • MI risk more important in older women and smokers

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