Risk Of Nonfatal Venous Thromboembolism Research Articles

Spironolactone use for acne is not associated with an increased risk of venous thromboembolism: A matched, retrospective cohort study

To the Editor: Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), and there have been concerns about whether the risk is even greater with drospirenone containing combined oral contraceptives. 1 Jick S.S. Hernandez R.K. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ. 2011; 342: d2151 Crossref PubMed Scopus (211) Google Scholar Drospirenone has antimineralocorticoid properties that may modify hemostasis leading to decreased coagulability. This provides a potential mechanism by which drospirenone containing COCs could result in an increased risk of thrombosis compared to other COCs. Since drospirenone is molecularly related to spironolactone, it is possible that spironolactone might also be associated with an increased risk for VTE. The purpose of this study was to evaluate whether patients with acne treated with spironolactone are at increased risk for VTE.

Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 μg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 μg (DRSP/EE30). Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data

Objective To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel.Design Nested case-control and cohort study.Setting...

Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data

Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data

There is a similar risk of nonfatal venous thromboembolism (VTE) between transdermal and oral contraceptives

There is a similar risk of nonfatal venous thromboembolism (VTE) between transdermal and oral contraceptives

There is a similar risk of nonfatal venous thromboembolism (VTE) between transdermal and oral contraceptives

There is a similar risk of nonfatal venous thromboembolism (VTE) between transdermal and oral contraceptives

Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 μg of ethinyl estradiol

Context In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing norgestimate and 35 μg of EE. Objective This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing norgestimate (either monophasic or triphasic) and 35 μg of EE (norgestimate-35) using an additional 17months of data. Design, Setting and Participants Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. Main Outcome Measures Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. Results We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to norgestimate-35 was 1.1 (95% CI 0.6–2.1). Conclusions After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 μg of EE and norgestimate.

Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 μg of ethinyl estradiol

Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 μg of ethinyl estradiol

The risk of nonfatal venous thromboembolism (VTEs) appears to be similar with either transdermal or oral contraceptive (OC) use,

The risk of nonfatal venous thromboembolism (VTEs) appears to be similar with either transdermal or oral contraceptive (OC) use,

The risk of nonfatal venous thromboembolism (VTEs) appears to be similar with either transdermal or oral contraceptive (OC) use,

The risk of nonfatal venous thromboembolism (VTEs) appears to be similar with either transdermal or oral contraceptive (OC) use,

Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel

Context Previous studies have reported that users of the “third-generation” oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of norgestimate-containing OCs compared to other OCs, however, are lacking. Objective The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel. Design, Setting and Participants Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing norgestimate with 35 μg of ethinyl estradiol (EE), desogestrel with 30 μg of EE or levonorgestrel with 30 μg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs. Results Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8–1.6] and 1.7 (95% CI, 1.1–2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5–36.5), 53.5 (95% CI, 42.9–66.0) and 27.1 (95% CI, 21.1–34.3) per 100,000 woman-years for users of norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8–1.5) and 2.0 (95% CI, 1.4–2.7), respectively. Conclusions The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.

Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 μg of ethinyl estradiol

Context There is concern that a new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin increases the risk for venous thromboembolism (VTE) compared to previously marketed oral contraceptives (OCs). Objective Quantitative information was obtained on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using OCs, norgestimate (either monophasic or triphasic) and 35 μg EE (norgestimate-35), an OC that has been marketed for over a decade. Design, Setting and Participants Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women aged 15 to 44, who started either the contraceptive patch or norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE). Up to four controls were matched to each case by age and calendar time. Main Outcome Measures Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives and incidence rates of nonfatal VTE for new users of each of the study contraceptives. Results We identified 68 newly diagnosed, idiopathic cases of VTE in the study population. In the case-control analysis, the OR comparing the contraceptive patch to norgestimate-35 was 0.9 (95% CI 0.5–1.6). The overall incidence rate for VTE was 52.8 per 100,000 women-years (95% CI 35.8–74.9) among users of the contraceptive patch and 41.8 per 100,000 women-years among users of norgestimate-35 (95% CI 29.4–57.6), and the age-adjusted VTE incidence rate ratio (IRR) for current use of the contraceptive patch vs. norgestimate-35 was 1.1 (95% CI 0.7–1.8). Conclusions The risk of nonfatal VTE for the contraceptive patch is similar to the risk for OCs containing 35 μg ethinylestradiol and norgestimate.

Hemostatic effects of third- and second-generation oral contraceptives: absence of a causal mechanism for a difference in risk of venous thromboembolism

Some observational studies have found a difference in the risk of nonfatal venous thromboembolism (VTE) with low-dose, oral contraceptives (OCs) containing desogestrel (DSG) or gestodene (GSD) and those containing levonorgestrel (LNG). However, this does not agree with current pathophysiological concepts. This review compares all 17 comparative studies on the hemostatic effects of DSG/GSD- and LNG- or norgestimate (NGM)-containing OCs, and comments on two recent cross-sectional studies on the effects of third- and second-generation OCs on activated protein C (APC) sensitivity. In the comparative studies, the only difference in hemostatic parameters between DSG/GSD- and LNG- or NGM-containing OC users was a tendency towards higher factor VII (FVII) levels with DSG/GSD OCs. Differential effects on APC sensitivity were observed with the endogenous thrombin generation potential (ETP) assay, but not with the classical APC resistance test. FVII is not a risk marker for VTE, but is affected by dietary fat, estrogens and androgens and may interfere with the ETP assay. As no differences in established VTE risk markers were observed, there is no plausible reason for a differential risk of VTE with DSG/GSD- and LNG-containing OCs. In fact, the lack of differences with regard to established risk markers of VTE gives further support to the findings of the most recent epidemiological studies, which have not found any difference in the risk of VTE between third- and second-generation OCs.

Combined oral contraception and the risk of venous thromboembolism.

The "pill scare" of 1995 (triggered by the recommendation of the UK Committee on Safety of Medicines that users of third-generation formulations switch to second-generation pills) created a need for re-education of both the medical profession and the general public about the risks and benefits of combined oral contraceptives (OCs). The 1995 announcement led to widespread confusion and mistrust, as well as discontinuation of all OC use on the part of many of the 1.5 million UK users of third-generation pills. An estimated 10,000 more induced abortions and 30,000 more conceptions than expected from previous patterns occurred in the 9 months following the Committee's announcement. Ironically, the risk of nonfatal venous thromboembolism associated with pregnancy is twice that associated with the use of third-generation OCs. Ways must be found to keep women, physicians, and other health care professionals informed about the latest research findings and their clinical implications without creating a recurrence of the 1995 panic. Research data should be presented in terms of both the absolute and relative risks, and drug safety issues should be debated among the experts before premature pronouncements are issued through the mass media.

Risk Factors for Fatal Venous Thromboembolism in Young Women: A Case-Control Study

A case-control study of fatal venous thromboembolism in young women is described. Sixty women aged between 16 and 39 who died from thromboembolism in England and Wales between 1986 and 1988 were included in the study. Two living controls matched for age and marital status were sought from the records of the general practitioner with whom each case was registered. Some 115 controls were included in the study. The cases had a significantly higher prevalence of a history of major illness, particularly thrombotic episodes, than the controls. The odds ratio (OR) of a fatal thromboembolism in women who had a history of venous thrombosis was 4.0 (95% Cl: 1.4-11.5). There was also a significantly higher frequency of a recent operation or accident amongst the cases than the controls (OR = 11.1, 95% Cl: 1.3-92.5). There was no significant excess or oral contraceptive use amongst the cases. The overall OR associated with current use of oral contraceptives was 1.6 (95% Cl: 0.7-3.4), while the corresponding OR for 'idiopathic' diseases was 2.1 (95% Cl: 0.8-5.2). These risks are considerably smaller than those observed in previous studies. The observed risk may be low because the dosage of oestrogen in modern oral contraceptive preparations has been reduced, but it may also be because the cases of fatal venous thromboembolism included in this study represent only a small proportion of all cases of venous thrombeombolism; a disease which is rarely fatal in young women. These results cannot necessarily be extrapolated to nonfatal venous thromboembolism.