First-time use of newer oral contraceptives and the risk of venous thromboembolism

Abstract

Recent epidemiologic studies reported that the risk of venous thromboembolism (VTE) was higher with the use of the newer third generation oral contraceptives than with second generation agents. Although the overall findings of these studies are similar, the results, as they relate to patterns and duration of oral contraceptive use particularly among first-time users, are inconsistent. We reanalyzed data from the Transnational case-control study to assess the risk of VTE associated with first-time use of oral contraceptives as a function of its duration of use. Over the period 1993 to 1995, 471 cases of venous thromboembolism were identified in Germany and the United Kingdom. For each case, up to four controls were obtained, for a total of 1772 controls. Data on oral contraceptive use and confounding variables, including data on sociodemographic, lifestyle, medical history, and family history of disease, were obtained by interview. Data analysis was based on the 105 cases and 422 controls who were first-time users of second or third generation agents, or never users of oral contraception. Rate ratios, adjusted for confounders and approximated by odds ratios, were estimated as a continuous function of duration of oral contraceptive use by logistic regression and quadratic spline models. We found, for first-time users, that the adjusted rate ratio of VTE as a function of the duration of oral contraceptive use is essentially identical for second and third generation pills relative to never users. This rate ratio increases to around 10 in the first year of use and decreases to around two after 2 years of use, remaining at this risk level thereafter for both second and third generation agents. We conclude that second and third generation agents are associated with identical risks of venous thromboembolism when they are prescribed to women who are using oral contraceptives for the first time ever.

PIP: Recent epidemiologic studies reported that the risk of venous thromboembolism (VTE) was higher with the use of the newer third-generation oral contraceptives (OCs) than with second-generation agents. Although the overall findings of these studies are similar, the results, as they relate to patterns and duration of OC use, particularly among first-time users, are inconsistent. The authors reanalyzed data from the transnational case-control study to assess the risk of VTE associated with first-time use of OCs as a function of its duration of use. Over the period 1993-95, 471 cases of VTE were identified in Germany and the UK. For each case, up to 4 controls were obtained, for a total of 1772 controls. Data on OC use and confounding variables, including data on sociodemographic, lifestyle, medical history, and family history of disease, were obtained by interview. Data analysis was based on the 105 cases and 422 controls who were first-time users of second- or third-generation agents or never-users of OCs. Rate ratios, adjusted for confounders and approximated by odds ratios, were estimated as a continuous function of duration of OC use by logistic regression and quadratic spline models. The authors found, for first-time users, that the adjusted rate ratio of VTE as a function of the duration of OC use is essentially identical for second- and third-generation pills relative to never-users. This rate ratio increases to about 10 in the first year of use and decreases to about 2 after 2 years of use, remaining at this risk level thereafter for both second- and third-generation agents. The authors conclude that second- and third-generation agents are associated with identical risks of VTE when they are prescribed to women who are using OCs for the first time ever.