Glucocorticoid use and risk of first and recurrent venous thromboembolism: self-controlled case-series and cohort study.

Glucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to determine. The aim of our present study was to quantify the risk for first and recurrent VTE associated with oral glucocorticoids use, considering the underlying disease. A total of 2547 patients with VTE from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study were linked to the Dutch Pharmaceutical Statistics register. The risk of first VTE during periods of exposure with oral glucocorticoids was estimated by the self-controlled case series method and that of recurrent VTE was examined in a cohort design. The incidence rate ratio (IRR) of first VTE in the period of glucocorticoid treatment was 3·51 [95% confidence interval (CI) 2·55-4·80]. This IRR was 2·53 (95% CI 1·10-5·72) in the week before treatment started, 5·28 (95% CI 2·89-9·53) in the first 7 days of treatment, remained elevated afterwards and decreased to 1·55 (95% CI 0·85-3·12) after 6 months, as compared to unexposed periods. The hazard ratio for recurrence was 2·72 (95% CI 1·64-4·78) in treatment periods as compared with no treatment. The increased risk of VTE associated with oral glucocorticoid treatment is due to a combined effect of the treatment and the underlying disease, remaining high during the first months of prescription.

Risk of recurrent venous thromboembolism related to prior risk situations: re-evaluation of a cohort study with a longer follow-up.

: Venous thromboembolism (VTE) is a chronic disease. Strategies to assess groups at a high risk of recurrence are needed. We reported that patients without prior risk situation for VTE had an incidence rate ratio (IRR) three times higher when compared with those with this history. The aim of this study was to re-evaluate the cohort, with a longer follow-up and evaluated the association between the absence of a prior risk situation for VTE with an increased risk for recurrence. A total of 289 patients with a previous VTE were followed for 116 months. Patients were advised to attend the outpatients' clinic in case of suspected VTE recurrence. Incidence rates of recurrent thrombotic events were calculated as the number of events over the accumulated observation time. Recurrent VTE occurred in 52 (18%) patients. Patients with a provoked first event and positive prior risk situations for VTE had an incidence rate for recurrence of 1.2 [95% confidence interval (95% CI), 0.7-1.9] per 100 patient-years. The IRR of this subgroup compared with patients with a provoked event without prior risk situations for VTE was 0.9 (95% CI 0.4-2.4). IRR was 2.5 (95% CI, 1.3-4.9) in patients with an unprovoked event and positive prior risk situations and 5.9 (95% CI, 32.8-12.5) in patients with an unprovoked event and no prior risk situations compared with patients with a provoked event without other prior risk situations for VTE. Exposure to prior risk situations for VTE was a protective factor among those patients whose first VTE event was unprovoked.

Association of apolipoproteins C-I, C-II, C-III and E with coagulation markers and venous thromboembolism risk.

PURPOSE: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic properties and are associated with risk of venous thromboembolism (VTE). PATIENTS AND METHODS: A total of 127 VTE patients and 299 controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (1999-2004), in the Netherlands. The apolipoproteins were quantified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuous variable (per SD increase). RESULTS: In controls, increases in levels of apolipoproteins were associated with increases in levels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time. Additionally, increasing apolipoproteins C-III and E levels were associated with higher factor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associated with any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III, CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98-1.49), 1.19 (95% CI, 0.99-1.44), 1.24 (95% CI, 0.95-1.61) and 1.06 (95% CI, 0.87-1.30) per SD increase, respectively. These odds ratios did not attenuate after adjustments for statin use, estrogen use, BMI, alcohol use, and self-reported diabetes. CONCLUSIONS: Levels of apolipoproteins C-I, C-II, C-III and E are associated with those of several coagulation factors. However, whether these apolipoproteins are also associated with an increased risk of VTE remains to be established.

Statin Therapy to Revert Hypercoagulability and Prevent Venous Thromboembolism: A Narrative Review.

Venous thromboembolism (VTE) causes a major disease burden worldwide, so that effective preventive measures are warranted. Although oral anticoagulation is effective in preventing VTE episodes, bleeding complications are a major concern that may lead to treatment avoidance. Statin therapy, which is widely used for prevention of arterial cardiovascular disease, is a promising alternative treatment for VTE prophylaxis, as the drug may affect hemostasis without increasing the risk of bleeding. In the past years, clinical studies have suggested that statins can interfere with blood coagulation and, in turn, reduce the risk of VTE. These effects, however, are still regarded with skepticism, as the underlying mechanisms by which statins may affect hemostasis in humans are not clear and data showing that statin therapy reduces VTE risk mostly came from observational studies, while only one randomized trial was conducted to evaluate this issue. In this review, the authors summarize the currently available evidence regarding the effect of statin therapy on coagulation and on VTE prevention. Recent randomized data showed that statin therapy, in particular rosuvastatin, leads to decreased levels of coagulation factors in patients with prior VTE. This evidence provides a reasonable basis for interventional studies necessary to establish the efficacy of statins on reducing the risk of incident and recurrent VTE.

Rosuvastatin use reduces thrombin generation potential in patients with venous thromboembolism: a randomized controlled trial.

Essentials The role of statins in hemostasis and venous thromboembolism (VTE) prophylaxis is not clear. This trial assessed whether rosuvastatin use affects thrombin generation in patients with VTE. Endogenous thrombin potential and peak were decreased by 10% and 5% with rosuvastatin therapy. These results provide basis for trials on the efficacy of statins in reducing recurrent VTE risk. SUMMARY: Background Statin therapy could form an alternative prophylactic treatment for venous thromboembolism (VTE) if statins are proven to downregulate hemostasis and prevent recurrent VTE, without increasing bleeding risk. Objectives The STAtins Reduce Thrombophilia (START) trial investigated whether statin affects coagulation in patients with prior VTE. Patients/methods After anticoagulation withdrawal, patients were randomized to rosuvastatin 20 mg day-1 for 4 weeks or no intervention. Plasma samples taken at baseline and at the end of the study were analyzed employing thrombin generation assay. Results and conclusions The study comprised 126 rosuvastatin users and 119 non-users. Mean age was 58 years, 61% were men, 49% had unprovoked VTE and 75% had cardiovascular (CV) risk factors. Endogenous thrombin potential (ETP) increased from baseline to end of study in non-statin users (mean 97.22 nm*min; 95% CI, 40.92-153.53) and decreased in rosuvastatin users (mean -24.94 nm*min; 95% CI, -71.81 to 21.93). The mean difference in ETP change between treatments was -120.24 nm*min (95% CI, -192.97 to -47.51), yielding a 10.4% ETP reduction by rosuvastatin. The thrombin peak increased in both non-statin (mean 20.69 nm; 95% CI, 9.80-31.58) and rosuvastatin users (mean 8.41 nm; 95% CI -0.86 to 17.69). The mean difference in peak change between treatments was -11.88 nm (95% CI, -26.11 to 2.35), yielding a 5% peak reduction by rosuvastatin. Other thrombin generation parameters did not change substantially. The reduction in ETP and peak by rosuvastatin was more pronounced in the subgroups of participants with CV risk factors and with unprovoked VTE. We conclude that rosuvastatin reduces thrombin generation potential in patients who had VTE.

Risk of recurrent venous thrombosis related to past provoking risk situations: follow-up of a cohort study.

Strategies targeting at classifying the risk for recurrent venous thrombosis are needed. We previously hypothesized, by studying a cohort of patients, that those who had 'survived' risk situations for venous thrombosis without developing it would, after a first venous thrombosis, have a low recurrence risk. Therefore, we re-evaluated the same cohort, now with a longer follow-up. Patients, after a first confirmed venous thrombosis event, were followed for an average of 43 months after suspension of anticoagulation. Patients with indication for indefinite anticoagulation were not included. The primary endpoint was objective recurrent venous thrombosis. Recurrent venous thrombosis was recorded in 9% of 378 eligible patients. Patients with a provoked first event and positive past risk situations for venous thrombosis had an incidence rate of recurrence of 1.26 (95% CI, 0.60-2.31) per 100 patient-years. The incidence rate ratio (IRR) of this subgroup compared with patients with a provoked event without other past risk situations for venous thrombosis was 0.8 (95% CI 0.2-2.9). This IRR was 2.8 (95% CI, 1.2-6.5) in patients with an unprovoked event and positive past risk situations and 7.1 (95% CI, 3.0-17.1) in patients with an unprovoked event and no past risk situations. When only idiopathic first events were evaluated the IRR was 2.5 (95% CI, 1.1-5.9) for patients without past risk situation compared with those with these history. In this study, asking a patient about past exposure to risk factors for venous thrombosis long before the occurrence of a first venous thrombosis occurred, could be used to classify patients with a first unprovoked venous thrombosis at higher risk for recurrence of venous thrombosis.

Past provoking venous thrombosis risk situations on the risk of a recurrent thrombotic event: a cohort study.

OBJECTIVE: Strategies that can classify the risk for recurrent venous thrombosis are needed. Some patients may have experienced many risk situations during their life time without developing venous thrombosis (VT), while others may have experienced few of such risk factors and then develop VT idiopathically or after a single provoked risk factor. We hypothesized that those who had 'survived' many risk situations without developing VT would, after a first VT, have a low recurrence risk. METHODS: Brazilian tertiary hospital cohort was followed for an average of 30 months after anticoagulation withdrawal for a first VT. Patients with indication for indefinite anticoagulation were not included. The primary end point was objective recurrent VT. RESULTS: Recurrent VT was recorded in 7% of 378 eligible patients. Patients with a provoked first event and positive past risk situations for VT had an incidence rate of recurrence of 1.16 (95% confidence interval [CI], 0.47-2.39) per 100 patient-years. The incidence rate ratio (IRR) of this subgroup compared to patients with a provoked event without other past risk situations for VT was 1.1 (95% CI, 0.3-4.4). This IRR was 3.3 (95% CI, 1.3-8.7) in patients with an unprovoked event and positive past risk situations and 5.1 (95% CI, 1.6-16.1) in patients with an unprovoked event and no past risk situations. CONCLUSIONS: Asking a patient about past exposure of venous thrombosis risk factors long before the occurrence of a first venous thrombosis occurred, does not provide information to classify patients at lower risk for recurrence of venous thrombosis.