Oral contraceptives and venous thromboembolism: A five-year national case-control study

Herlev University Hospital, Herlev, Denmark.
Contraception (Impact Factor: 2.34). 03/2002; 65(3):187-96. DOI: 10.1016/S0010-7824(01)00307-9
Source: PubMed


The objective of this study was to assess the influence of oral contraceptives (OCs) on the risk of venous thromboembolism (VTE) in young women. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old, suffering a first ever deep venous thrombosis or a first pulmonary embolism (PE) during the period January 1, 1994, to December 30, 1998, were included. Controls were selected annually, 600 per year in 1994-1995 and 1200 per year 1996-1998. Response rates for cases and controls were 87.2% and 89.7%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic disease, 987 cases and 4054 controls were available for analysis. A multivariate, matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustment was made for confounding influence (if any) from the following variables: age, year, body mass index, length of OC use, family history of VTE, cerebral thrombosis or myocardial infarction, coagulopathies, diabetes, years of schooling, and previous birth. The risk of VTE among current users of OCs was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: <1 year, 7.0 (5.1-9.6); 1-5 years, 3.6 (2.7-4.8); and >5 years, 3.1 (2.5-3.8), all compared with nonusers of OCs. After adjustment for confounders, current use of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins when compared with nonuse resulted in ORs for VTE of 2.9 (2.2-3.8) and 4.0 (3.2-4.9), respectively. After adjusting for progestin types and length of use, the risk decreased significantly with decreasing estrogen dose. With 30-40 microg as reference, 20 and 50 microg products implied ORs of 0.6 (0.4-0.9) and 1.6 (0.9-2.8), respectively (p(trend) = 0.02). After correction for duration of use and differences in estrogen dose, the third/second-generation risk ratio was 1.3 (1.0-1.8; p <0.05). In conclusion, use of OCs was associated significantly to the risk of VTE. The risk among current users was reduced by more than 50% during the first years of use. The risk increased more than 100% with increasing estrogen dose, and the difference in risk between users of third- and second-generation OCs, after correction for length of use and estrogen dose, was 33%.

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Available from: Svend Kreiner, Dec 28, 2014
    • "CHCs contain both estrogen and a progestin and include combined oral contraceptives (COCs), the combined contraceptive vaginal ring and the combined transdermal contraceptive patch. Observational studies and meta-analyses have reported elevated risks of coronary heart disease, myocardial infarction (MI), stroke, venous thromboembolism (VTE) and peripheral arterial disease (PAD) among women who smoke and use CHCs [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29]. The mechanisms underlying increased CVD risk in female smokers who use CHCs are poorly understood but could include effects of products of combustion, nicotine exposure or both. "
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    ABSTRACT: Background: Women who use combined hormonal contraceptives and cigarettes have an increased risk for cardiovascular (CV) events. We reviewed the literature to determine whether women who use hormonal contraceptives (HC) and electronic cigarettes (e-cigarettes) also have an increased risk. Study design: Systematic review. Methods: We searched for articles reporting myocardial infarction (MI), stroke, venous thromboembolism, peripheral arterial disease, or changes to CV markers in women using e-cigarettes and HC. We also searched for indirect evidence, such as CV outcomes among e-cigarette users in the general population and among HC users exposed to nicotine, propylene glycol, or glycerol. Results: No articles reported on outcomes among e-cigarette users using HC. Among the general population, 13 articles reported on heart rate or blood pressure after e-cigarette use. These markers generally remained normal, even when significant changes were observed. In 3 studies, changes were less pronounced after e-cigarette use than cigarette use. One MI was reported among 1,012 people exposed to e-cigarettes in these studies. One article on nicotine and HC exposure found both exposures to be significantly associated with acute changes to heart rate, though mean heart rate remained normal. No articles on propylene glycol or glycerol and HC exposure were identified. Conclusion: We identified no evidence on CV outcomes among e-cigarette users using HC. Limited data reporting mostly acute outcomes suggested that CV events are rare among e-cigarettes users in the general population, and that e-cigarettes may affect heart rate and blood pressure less than conventional cigarettes. There is a need for research assessing joint HC and e-cigarette exposure on clinical CV outcomes.
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    • "Fold increase in VTE risk with familial history 3.000 2.3–4 [37] Fold increase in VTE risk with personal history 1.710 1.16–2.252 [38] Proportion of idiopathic VTE 0.365 0.27–0.46 "
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    ABSTRACT: In the Italian health care system, genetic tests for factor V Leiden and factor II are routinely prescribed to assess the predisposition to venous thromboembolism (VTE) of women who request oral contraception. With specific reference to two subpopulations of women already at risk (i.e., familial history or previous event of VTE), the study aimed to assess whether current screening practices in Italy are cost-effective. Two decisional models accrued costs and quality-adjusted life-years (QALY) annually from the perspective of the National Health Service. The two models were derived from a decision analysis exercise concerning testing practices and consequent prescribing behavior for oral contraception conducted with 250 Italian gynecologists. Health care costs were compiled on the basis of 10-year hospital discharge records and the activities of a thrombosis center. Whenever possible, input data were based on the Italian context; otherwise, the data were taken from the international literature. Current testing practices on women with a familial history of VTE generate an incremental cost-effectiveness ratio of €72,412/QALY, which is well above the acceptable threshold of cost-effectiveness of €40,000 to €50,000/QALY. In the case of women with a previous event of VTE, the most frequently used testing strategy is cost-ineffective and leads to an overall loss of QALY. This study represents the first attempt to conduct a cost-utility analysis of genetic screening practices for the predisposition to VTE in the Italian setting. The results indicate that there is an urgent need to better monitor the indications for which tests for factor V Leiden and factor II are prescribed.
    Full-text · Article · Sep 2013 · Value in Health
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    • "The third generation OC pills are associated with the highest VTE risk [11]. OC administration is associated with a prothrombotic state [1] [11], which is reflected by higher plasma D-dimer, C-reactive protein (CRP), tissue plasminogen activator (tPA) and coagulation factors II, VII, and X. Those alterations have been shown to be in part counterbalanced by profibrinolytic effect mediated by increased plasminogen and reduced PAI-1 activity and its antigen [1,12]. "
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    ABSTRACT: Oral contraceptives (OC) in the presence of factor V Leiden mutation (FVL) markedly increase the risk of venous thromboembolism (VTE). Little is known about the OC and FVL-related alterations in fibrin clot properties. Plasma fibrin clot permeability (K(s)) and efficiency of lysis, reflected by clot lysis time (CLT) and the rate of D-dimer release from clots (D-D(rate)) induced by recombinant tissue plasminogen activator (tPA) were determined in 25 women with a family history of VTE who were heterozygous for FVL [FVL(+/-) - twice, on third-generation OC and after their discontinuation. Female non-carriers of FVL, matched for demographics, using OC and after their discontinuation served as controls (n=25). All participants had no personal history of VTE. OC discontinuation in FVL(+/-) women resulted in shortened CLT (-9%), and increased K(s) (+4%) and D-D(rate) (+1.4%; all p<0.01). Alterations in fibrin clot properties were associated with decreased prothrombin fragments 1+2 (F1+2) (-8%), plasminogen activator inhibitor-1 (PAI-1) antigen (-11%), and thrombin activatable fibrinolysis inhibitor (TAFI) activity (-20%; all p<0.01). During OC use FVL(+/-) carriers compared with non-carriers had higher platelet count, activity of PAI-1, TAFI, and tPA, as well as prolonged CLT and higher D-D(max), along with lower D-D(rate) and K(s). Multiple regression analysis adjusted for fibrinogen and age, showed that PAI-1 antigen and TAFI activity independently predicted CLT in FVL(+/-) women on OC. FVL(+/-) is associated with hypofibrinolysis in apparently healthy women and third-generation OC administration unfavorably alters plasma clot characteristics in female FVL(+/-) carriers with a family history of thrombotic events.
    Full-text · Article · Aug 2012 · Thrombosis Research
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