Venous thromboembolism case study

Perez-Gutthan S, Garcfa-Rodriguez LA, Castellsague J, Duque-Oliart A (1997) Hormone replacement therapy and risk of venous thromboembolism population based case-control study. Br Med J 314 796-800... 

Tamoxifen users present also a doubling incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) (118 vs. 62 cases). This increase is similar to that seen with HRT. There are some aspects of this side effect that should be commented on to improve the management of women eligible for tamoxifen treatment and at risk for DVT (Goldhaber 2005). In the subanalysis of the Italian study (Decensi et al. 2005), the venous thromboembolism definition included DVT, PE, and superficial phlebitis. Most of the VTE that the authors reported were, in fact, cases of superficial phlebitis, whereas the admitted definition of venous thromboembolism excludes this entity. Such conceptual differences, together with differences in age and background characteristics between the four studies, can explain the diversity in the incidences observed. 

Cyproterone acetate in combination with ethinylestra-diol is indicated for the treatment of women with severe acne and moderately severe hirsutism. This product has been associated with a greater risk of venous thromboembolism than oral contraceptives. However, in a rigorous case-control study the risk of venous thromboembolism with cyproterone acetate + ethinylestradiol was not significantly greater than the risk in women who took conventional oral contraceptives (25). 

England that the Committee on Safety of Medicines had written to prescribers in 1995 stating that three unpublished studies on the safety of combined oral contraceptives in relation to venous thromboembolism had indicated about a two-fold increase in the risk of such conditions compared with the preceding generation of products. This issue of a two-fold increase became crucial to the case. For reasons of causation, as the Judge put it, the claimants had accepted the burden of proving that the increase in risk was not less than two-fold. 

Thorogood M, Mann J, Murphy M, Vessey M. Risk factors for fatal venous thromboembolism in young women a case-control study. Int J Epidemiol 1992 21(l) 48-52. 

Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism a five-year national case-control study. Contraception 2002 65(3) 187-96. 

There is other evidence that transdermal estrogen replacement therapy has relatively little effect on hemostasis. In a case control study, 155 consecutive patients with a first documented episode of idiopathic venous thromboembolism, 92 of whom had had a pulmonary embolism and 63 a deep venous thrombosis, were compared with 381 healthy matched controls (88). Overall, 32 (21%) of the cases and 27 (7%) of the controls were current users of oral estrogen replacement therapy, whereas 30 (19%) cases and 93 (24%) controls were current users of transdermal estrogen replacement therapy. After adjustment for potential confounding variables, the odds ratios for venous thromboembolism in current users of oral and transdermal estrogen replacement therapy compared with non-users were 3.5 (95% Cl = 1.8, 6.8) and 0.9 (0.5, 1.6) respectively. Estimated risk for venous thromboembolism in current users of oral estrogen replacement therapy compared with transdermal users was 4.0 (1.9, 8.3). 

In a case-control study 155 postmenopausal women who had had venous thromboembolism were compared with 381 matched controls (91). In all, 32 cases and 27 controls were current users of oral replacement therapy, whereas 30 cases and 93 controls were current users of transdermal products. After adjustment for potential confounding variables, the estimated risk ratio for venous thromboembolism in current users of the oral products compared with the transdermal users was 4.0 (1.9-8.3). This is strong evidence that the transdermal route was considerably safer. However, the conclusions of different studies continue to conflict with one another, no doubt in part because of variations in the formulations and patterns of use of the products. 

Hoibraaten E, Abdelnoor M, Sandset PM. Hormone replacement therapy with estradiol and risk of venous thromboembolism—a population-based case-control study. Thromb Haemost 1999 82(4) 1218-21. 

Spitzer WO, Lewis MA, Heinemann LA, Thorogood M, MacRae KD. Third generation oral contraceptives and risk of venous thromboembolic disorders an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996 312(7023) 83-8. 

Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism a case-control study. Lancet 2000 356(9237) 1219-23. 

Nakanuma, Y., Ohta, G., Kurumaya, H., Tanino, M., Doishita, K., Takayanagi, N., Rin, S. Pathological study on livers with noncirrhotic portal hypertension and portal venous thromboembolic occlusion report of seven autopsy cases. Amer. J. Gastroenterol. 1984 79 782- 789... 

Case-control studies have been used extensively to assess the safety of pharmaceuticals. There are many examples of case-control studies that have identified important associations between drugs and adverse health events vaginal cancer and diethylstilbestrol, Reye s syndrome and aspirin, peptic ulcer disease and nonsteroidal antiinflammatory drugs, and venous thromboembolism and oral contraceptives. Data from case-control studies are used to calculate an odds ratio, which is the ratio of the odds of developing the disease for exposed patients to the odds of developing the disease for unexposed patients. 

Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk of venous thromboembolism nested case-control study. BMJ 2010 341 c4245. 

Cardiovascular In some cases tibolone prevents bone loss in elderly subjects, although after 40 years of use some questions regarding its clinical role remain unanswered. In a randomized study in the US, in which 4538 older women took either tibolone 1.25 mg/day or placebo, tibolone reduced the risk of vertebral fractures and of breast cancer. However, there was an increased risk of stroke (relative hazard = 2.19 95% Cl = 1.14, 4.23) the study was stopped after a mean treatment period of 34 months at the recommendation of the data and safety monitoring board [83. There were no significant differences between the two groups in the risks of either coronary heart disease or venous thromboembolism. 

Johannesdottir SA, Horvath-Puho E, Dekkers OM, Cannegieter SC, Jorgensen JO, Ehrenstein V, et al. Use of glucocorticoids and risk of venous thromboembolism a nationwide population-based case-control study. JAMA Intern Med 2013 173(9) 743-52. 

Sartwell PE, et al. Oral contraceptives and relative risk of death from venous and pulmonary thromboembolism in the United States an epidemiologic case-control study. Am J Epidemiol 1969 90 365. 

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