Cost-effectiveness of rivaroxaban versus warfarin anticoagulation for the prevention of recurrent venous thromboembolism: A U.S. perspective

Introduction

Rivaroxaban is an oral direct factor Xa inhibitor that is noninferior to warfarin in the prevention of recurrent venous thromboembolism (VTE). Whether rivaroxaban is cost-effective in the prevention of recurrent VTE, however, is not known.

Material and Methods

To assess the cost effectiveness of rivaroxaban compared with warfarin in the prevention of recurrent VTE, we built a Markov state-transition model over a 10-year time horizon. The base case analysis consisted of a hypothetical cohort of 60-year-old patients with an initial VTE who received secondary prophylaxis with either rivaroxaban or warfarin for 3 to 12 months. Cost estimates were derived from the Healthcare and Utilization Project and other sources. Probabilities were based on literature values. Outcomes included costs in 2011 United States dollars, quality-adjusted life-years (QALYs), and incremental cost effectiveness ratios (ICERs) over 10 years from a societal perspective.

Results

Compared with warfarin, the rivaroxaban strategy cost less ($3,195 vs. $6,188) and was more effective (9.29 QALYs vs 9.14 QALYs). Our results were highly robust in sensitivity analyses. Warfarin was no longer dominated by rivaroxaban when the risk of major bleeding with rivaroxaban exceeds 3.8% (base case estimate: 0.96%).

Conclusion

In summary, prophylactic anticoagulation with rivaroxaban appears to be a cost effective, and perhaps cost saving, alternative to warfarin for the prevention of recurrent VTE.     

Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation

Background

The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis.

Material/Methods

Prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23–25 until 8–10 weeks postpartum.

Results

Prothrombin fragments 1 + 2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5 mg/l were found in about 30% and 20% of the heterozygous carriers at 4–5 and 8–10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies.

Conclusion

Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5 mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation.     

Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis

Introduction

Patients with cancer-associated thrombosis are at a high risk of developing recurrent events despite anticoagulant therapy. Escalation of the dose of low molecular weight heparin (LMWH) has been suggested as a potential treatment option to manage these patients. We sought to confirm the benefit and risk of this management strategy in patients with recurrent cancer-associated thrombosis.

Material and Methods

A retrospective cohort study of consecutive cancer outpatients seen for management of a symptomatic recurrent cancer-associated thrombosis while on anticoagulation was undertaken. Objectively confirmed episodes of recurrent thrombosis were treated with either dose escalation of LMWH or initiation of therapeutic dose of LMWH in patients already anticoagulated with LMWH or vitamin K antagonist (VKA) respectively. Included patients were followed for a minimum of 3 months after the index recurrent event.

Results

Fifty-five cancer patients with a recurrent venous thromboembolism (VTE) despite anticoagulation were included. At the time of the recurrence, 89% of patients were on LMWH. The median time between the initial cancer-associated thrombosis to the index recurrent event was 2.3 months (range 0.1 to 30.4 months). Four patients (7.3%; 95% CI: 2.0 to 17.6%) had a second recurrent VTE during the 3-month follow-up period. Three patients (5.5%; 95% CI 1.1 to 15.1%) had major bleeding complications after dose escalation of LMWH. There were no recurrent fatal VTE or major bleeding episodes.

Conclusion

Escalating the dose of LMWH seems effective and safe for managing patients with recurrent cancer-associated thrombosis despite anticoagulant therapy.     

Risk factors for recurrent venous thromboembolism in young and middle-aged women

Background

It is a matter of debate whether women with an episode of VTE associated with estrogen have a lower risk of recurrence than women with an unprovoked VTE.

Objectives

To identify risk factors for recurrent VTE in women and to assess the risk of recurrent VTE associated with combined oral contraceptives (CHC) or menopausal hormone treatment (HT), compared to surgery-related and unprovoked VTE.

Patients/Methods

A cohort of 974 women aged 18–64 years with a first episode of VTE were followed-up for a median time of 5.2 years. All women were previously included as cases in the Swedish nation-wide case–control study “Thrombo Embolism Hormone Study” (TEHS). Hazard ratios for recurrence were calculated using univariable and multivariable Cox proportional hazards model.

Results

A total of 102 patients (10%) suffered from recurrent VTE. The annual rate of recurrence was 1.0% in patients with surgery/cast, 2.0% in patients with CHC/HT and 3.2% in patients with unprovoked first VTE. Adjusted hazards ratio (HR_a) for recurrence was 0.35 (95% CI 0.20-0.61) in women with VT provoked by surgery/cast while women with estrogen-associated VTE had a HR_a of 0.70 (95% CI 0.43-1.20) compared to women with unprovoked VTE.

Conclusion

Women 18–64 years are at low risk of recurrent VTE. Women with hormone associated VTE had a lower risk of recurrence than women with unprovoked VTE, but not as low as surgery/cast provoked VTE.     

Further evidence in support of the association between venous thrombosis and atherosclerosis: A case–control study

Introduction

Whether there is an association between venous thromboembolism (VTE) and atherosclerosis is still controversial.

Aims

In a case–control study conducted on subjects older than 50, we assessed the prevalence of symptomatic or subclinical atherosclerosis in a group of unselected patients with unprovoked VTE, and compared it with that of patients with secondary VTE and of matched control individuals free from VTE disorders.

Methods

Cases and controls were enquired about the presence of previous symptomatic manifestations of atherosclerosis. Those with a negative history underwent the ultrasound assessment of carotid arteries following a standardized procedure. An intima-media thickness higher than 0.9 mm or the detection of at least one carotid plaque was regarded as a subclinical manifestation of atherosclerosis. After adjusting for age, gender and risk factors for atherosclerosis, we calculated the odds ratio (OR) for symptomatic or subclinical atherosclerosis in patients with unprovoked VTE as compared to those with secondary VTE and controls.

Results

We recruited 100 patients with unprovoked VTE, 100 with secondary VTE and 100 control individuals. In patients with unprovoked VTE, the adjusted OR for symptomatic or subclinical atherosclerosis was 5.1 (95% CI, 2.0 to 13.1) in comparison to patients with secondary VTE, and 14.5 (95% CI, 5.8 to 36.3) in comparison to controls. The prevalence of atherosclerosis was higher in patients with secondary VTE than in controls (OR, 3.1; 95% CI, 1.6 to 6.1).

Conclusion

The results of this study confirm the presence of a strong association between venous thrombosis and atherosclerosis.     

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.     

Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism

Introduction

We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden.

Materials and Methods

39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression.

Results

Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181).

Conclusions

It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.     

Clinical characteristics of patients with factor V Leiden or prothrombin G20210A and a first episode of venous thromboembolism. Findings from the RIETE Registry

Background

The clinical characteristics of patients with factor V Leiden or prothrombin G20210A presenting with a first episode of venous thromboembolism (VTE) have not been thoroughly studied.

Methods

RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the clinical characteristics of patients with factor V Leiden, prothrombin G20210A, or no thrombophilia, at presentation with a first episode of VTE.

Results

As of May 2009, 22428 patients had been enrolled with a first episode of VTE. Of these, 345 had factor V Leiden, 261 had prothrombin G20210A, and 2399 tested negative. Sixty-two percent of the VTE episodes in women with factor V Leiden or prothrombin G20210A (40% in men) were associated with an acquired risk factor. Among women, pregnancy or contraceptive use accounted for 63% and 67% of such risk factors. Patients with factor V Leiden presented with pulmonary embolism (PE) less likely than those with prothrombin G20210A (31% vs. 51%; p < 0.001) or with negative testing (31% vs. 45%, p < 0.001). In addition, PE patients with Factor V Leiden presented with hypoxaemia (Sat O₂ levels < 90%) less likely than those with prothrombin G20210A (4.5% vs. 17%; p < 0.001) or with no thrombophilia (4.5% vs. 20%; p < 0.001).

Conclusions

Most VTE episodes in women (not men) with factor V Leiden or prothrombin G20210A were associated with an acquired risk factor (mostly pregnancy or contraceptive use). Only 4.5% of patients with factor V Leiden presenting with acute PE had hypoxaemia.     

Efficacy of low- molecular- weight- heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: a systematic review of randomized controlled trials

Background

Patients with malignancy have a 4-fold increase in the risk of developing a venous thrombosis and a 3-fold increase in risk of bleeding. Both low-molecular-weight-heparin (LMWH) and vitamin K antagonists (VKA) have been used for treatment of cancer-associated thrombosis. However, the best anticoagulation approach remains a matter of debate.

Objective

In adult patients with cancer and an acute venous thromboembolic event we sought to determine the rates of recurrent venous thromboembolism (VTE) and major hemorrhage when treated with prolonged LMWH therapy compared to vitamin-K antagonists.

Patients/Methods

A systematic literature search strategy was used to identify potential trials on MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Medline in-process using an OVID interface. Risk assessment of bias of randomized controlled trials (RCTs) was performed according to the Cochrane Collaboration-Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome measure was symptomatic VTE recurrence rate during the anticoagulation period. Relative risk (RR) was used as the primary measurement with 95% confidence intervals (CIs). Pooled measurements were calculated using random –effects and fixed-effects model.

Results

Five articles met our inclusion criteria. All compared LMWH and VKA for secondary prevention of VTE. The pooled RR of VTE recurrence was 0.53 (95% CI: 0.36-0.76; p = 0.007). The pooled RR of major bleeding was 0.98 (95% CI: 0.49-1.93, p = 0.95). Minor bleeding events and all cause mortality were similar between the 2 intervention arms.

Conclusions

The results of our review suggest that the long term use of LMWH after the acute first week of treatment is superior to VKAs for secondary prevention of venous thromboembolism in adult patients with cancer.     

A genetic association study of D-dimer levels with 50 K SNPs from a candidate gene chip in four ethnic groups

Introduction

D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.

Materials and Methods

We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.

Results

Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p < 2.0 × 10^− 6. The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p = 0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p = 0.006). No additional SNPs were significantly associated with D-dimer.

Conclusions

Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.     

Short-term exposure to high levels of air pollution as a risk factor for acute isolated pulmonary embolism

Background

The association between air pollution exposure and occurrence of venous thromboembolism is a matter of debate. This retrospective case-control study investigated the associations between one month’s exposure to elevated levels of different pollutants (i.e. PM₁₀, CO, NOx, O₃, SO_2, Benzene, Benzoapyrene, Nickel, Lead Arsenic) and the development of acute isolated pulmonary embolism (PE).

Methods

The cases included 33 patients consecutively admitted to Padua Hospital with an objectively proven diagnosis of acute unprovoked (i.e. without predisposing conditions) isolated (i.e. without deep vein thrombosis) PE. The control group consisted of 72 consecutive patients with objectively proven acute provoked (i.e. associated to predisposing conditions) isolated PE. Average mean concentrations of pollutants in the month before PE diagnosis were computed by monitors located at 2 different sites throughout the city of Padua, and were obtained from the Regional Agency for Environmental Protection.

Results

Individuals who had PM₁₀, NOx, Benzene, Benzoapyrene, Cadmium, and Lead exposure equal/above the 2nd tertile, measured in controls, showed a significant increase in the risk of unprovoked PE. In case of PM₁₀ and Benzoapyrene this risk was not affected after adjustment for possible confounders. In fact, in the multivariate logistic regression analysis, the OR values were 5.24 (95% CI: 1.52-18.12) for PM₁₀ and 3.95 (95% CI: 1.06-14.71) for Benzoapyrene exposure in the month before PE diagnosis.

Conclusions

Our results, although preliminary, identify short-term (i.e. one month) exposure to elevate levels of air pollutants as a possible risk factor for the development of acute isolated PE. Larger studies are needed to confirm our results.     

Cost-Effectiveness Analysis of Extended Duration Anticoagulation with Rivaroxaban to Prevent Recurrent Venous Thromboembolism

Introduction

Extended duration anticoagulation with rivaroxaban for an additional 6–12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~ 82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban.

Material and Methods

A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20 mg daily, compared to placebo using a Medicare perspective, a one-month cycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6–12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).

Results

Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY.

Conclusion

Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6–12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.     

Thrombomodulin-dependent effect of factor VLeiden mutation on factor XIII activation

Introduction

Factor V Leiden mutation (FV_Leiden) is associated with impaired down-regulation of activated FV procoagulant activity and loss of FV anticoagulant function that result in an increased risk of venous thromboembolism. As the downstream effects of FV_Leiden on clot formation and fibrinolyis have only partially been revealed, we investigated its effect on the activation of factor XIII (FXIII) and the cross-linking of fibrin.

Methods

In the plasma samples of fifteen healthy individuals with known FV genotypes coagulation was initiated by recombinant human tissue factor and phospholipids with or without recombinant human thrombomodulin (rhTM). FV deficient plasma supplemented with purified wild type FV or FV_Leiden were also investigated. Clots were recovered and analyzed by SDS-PAGE and quantitative densitometric evaluation of Western blots.

Results

rhTM considerably delayed the activation of FXIII in the plasma from FV wild type individuals. This effect of rhTM was significantly impaired in the plasma from FV_Leiden carriers. The results were confirmed in experiments with FV deficient plasma supplemented by FV prepared from wild type individuals or FV_Leiden homozygotes. Fibrin γ-chain dimerization was also considerably delayed by rhTM in plasma samples from individuals without Leiden mutation, but not in plasma samples from FV_Leiden heterozygotes or homozygotes. The difference between heterozygotes and homozygotes was not statistically significant.

Conclusion

The highly diminished delaying effect of TM on FXIII activation and on the cross-linking of fibrin in FV_Leiden carriers might represent a novel mechanism contributing to the increased thrombosis risk of these individuals.     

Selective tissue factor/factor VIIa Inhibitor,ER-410660, and its prodrug,E5539, have anti-venous and anti-arterial thrombotic effects with a low risk of bleeding

Introduction

Many anticoagulant drugs target factors common to both the intrinsic and extrinsic coagulation pathways, which may lead to bleeding complications. Since the tissue factor (TF)/factor VIIa complex is associated with thrombosis onset and specifically activates the extrinsic coagulation pathway, compounds that inhibit this complex may provide therapeutic and/or prophylactic benefits with a decreased risk of bleeding.

Materials and Methods

The in vitro enzyme profile and anticoagulation selectivity of the TF/VIIa complex inhibitor, ER-410660, and its prodrug E5539 were assessed using enzyme inhibitory and plasma clotting assays. In vivo effects of ER-410660 and E5539 were determined using a TF-induced, thrombin generation rhesus monkey model; a stasis-induced, venous thrombosis rat model; a photochemically induced, arterial thrombosis rat model; and a rat tail-cut bleeding model.

Results

ER-410660 selectively prolonged prothrombin time, but had a less potent anticoagulant effect on the intrinsic pathway. It also exhibited a dose-dependent inhibitory effect on thrombin generation caused by TF-injection in the rhesus monkey model. ER-410660 also reduced venous thrombus weights in the TF-administered, stasis-induced, venous thrombosis rat model and prolonged the occlusion time induced by arterial thrombus formation after vascular injury. The compound was capable of doubling the total bleeding time in the rat tail-cut model, albeit with a considerably higher dose compared to the effective dose in the venous and arterial thrombosis models. Moreover, E5539, an orally available ER-410660 prodrug, reduced the thrombin-anti-thrombin complex levels, induced by TF-injection, in a dose-dependent manner.

Conclusion

Selective TF/VIIa inhibitors have potential as novel anticoagulants with a lower propensity for enhancing bleeding.     

Differences in Thrombotic Risk Factors in Black and White Women with Adverse Pregnancy Outcome

Introduction

Black women have an increased risk of adverse pregnancy outcomes and the characteristics of thrombotic risk factors in this population are unknown. The objective of this study was to examine the racial differences in thrombotic risk factors among women with adverse pregnancy outcomes.

Methods

Uniform data were collected in women with adverse pregnancy outcomes (pregnancy losses, intrauterine growth restriction (IUGR), prematurity, placental abruption and preeclampsia) referred to Thrombosis Network Centers funded by the Centers for Disease Control and Prevention (CDC).

Results

Among 343 white and 66 black women seen for adverse pregnancy outcomes, protein S and antithrombin deficiencies were more common in black women. The prevalence of diagnosed thrombophilia was higher among whites compared to blacks largely due to Factor V Leiden mutation. The prevalence of a personal history of venous thromboembolism (VTE) did not differ significantly by race. A family history of VTE, thrombophilia, and stroke or myocardial infarction (MI) was higher among whites. Black women had a higher body mass index, and a higher prevalence of hypertension, while the prevalence of sickle cell disease was approximately 27 fold higher compared to the general US black population.

Conclusions

Thrombotic risk factors differ significantly in white and black women with adverse pregnancy outcomes. Such differences highlight the importance of considering race separately when assessing thrombotic risk factors for adverse pregnancy outcomes.     

Case fatality of bleeding and recurrent venous thromboembolism during,initial therapy with direct oral anticoagulants: A systematic review

Introduction

The frequency and case fatality of venous thromboembolism (VTE) and major bleeding during the initial 3 months of therapy in those treated for symptomatic VTE with either direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA) are important clinically relevant outcomes. We sought to measure it during the initial months of anticoagulation for symptomatic VTE.

Material and Methods

We searched MEDLINE, EMBASE, and CENTRAL to identify studies that enrolled patients with acute symptomatic VTE treated with DOACs or VKA and reported data on bleeding, VTE recurrence and death. Studies were evaluated according to a priori inclusion criteria and critically appraised using established internal validity criteria. Single-proportion random-effects models were used to pool estimates.

Results

Of the 2453 citations retrieved, 5 RCTs that enrolled 24,507 patients were included. The rate of major bleeding was 1.8 (95% CI: 1.3-2.5) and 3.1 (95% CI: 2.4-3.9) per 100 patient-years in DOAC and VKA arms, respectively. The rate of VTE recurrence was 3.7 (95% CI: 2.7-4.7) and 4.1 (95% CI: 3.0-5.4) per 100 patient-years of DOAC and VKA, respectively. The case fatality rate of bleeding was significantly higher in the VKA arms 10.4% (95% CI: 6.6-15.4) compared to DOACs 6.1% (95% CI: 2.7-11.7; p value for difference = 0.029) with no statistical difference between the case fatalities for recurrent VTE. The rate of death from either definite major bleeding or definite recurrent VTE was 0.27 (95% CI: 0.16-0.40) and 0.46 (95% CI: 0.32-0.63) per 100 patient-years for DOACs and VKAs respectively, resulting in a number needed to treat of 875 for DOACs to prevent one death.

Conclusion

DOACs are attractive alternatives to VKAs for initial treatment of symptomatic VTE, with lower frequency and case fatality for major bleeding. However, the incremental safety benefit of DOACs over VKAs is small, with large numbers needed to treat.     

Thromboprophylaxis use and concordance with guidelines among medical and surgical patients in Morocco

Introduction

No data are available on thromboprophylaxis use in Morocco. Our aim was to characterize patients at risk of venous thromboembolism and assess the rate of appropriate thromboprophylaxis.

Materials and Methods

This was a national, observational, multicentre survey of venous thromboembolism risk and thromboprophylaxis use in hospitalized patients. Data were collected on a predefined date in three university hospitals in Morocco using a standardized pre-printed form. Thromboembolic risk was assessed according to the American College of Chest Physicians (ACCP) 2008 guidelines. Patients were classified as “thromboprophylaxis indicated” or “thromboprophylaxis not indicated”.

Results

784 patients were analysed: 307 (39.2%) medical and 477 (60.8%) surgical. 421 (53.7%) were female. Medical patients were older than surgical patients (57.6 ± 11.5 vs. 46.2 ± 16.9 years, p < 0.0001) and were more likely to have risk factors for thromboembolism (50.5% vs. 45.7% of patients, p = NS). 57% of patients without contraindications or bleeding risk were at risk of thromboembolism according to ACCP guidelines and thromboprophylaxis was prescribed to 42.8% of these patients. In contrast, 7.4% of patients with no thromboembolic risk also received thromboprophylaxis (proportion agreement: 61.0%; Kappa = 0.296). Over half (54.5%) of medical patients at risk of thromboembolism did not receive thromboprophylaxis whereas 6.3% of those with no risk did receive it (proportion agreement: 76.4%; Kappa = 0.433). These figures were 57.9% and 9.2%, respectively, for surgical patients (proportion agreement: 52.7%; Kappa = 0.191). Thromboprophylaxis was given to 19.2% of patients with contraindications or a bleeding risk.

Conclusions

Educational initiatives are imperative to inform doctors about appropriate thromboprophylaxis.     

Serum Lipoprotein (a) Levels in Patients with First Unprovoked Venous Thromboembolism is not Associated with Subsequent Risk of Recurrent VTE

Introduction

Case-control studies suggest that elevated lipoprotein (a) (Lp(a)) is a risk factor for first venous thromboembolism (VTE). Lp(a) has not been prospectively investigated as a possible risk factor for recurrent VTE in first unprovoked VTE patients. We sought to determine if serum Lp(a) levels in patients with unprovoked VTE who discontinue anticoagulants after 5 to 7 months of therapy predict VTE recurrence in a prospective cohort study.

Materials and Methods

Serum Lp(a) measurements were obtained from 510 first unprovoked VTE patients treated for 5 -7 months with anticoagulants in a 12 center study. Patients were subsequently followed for a mean of 16.9 months (SD ± 11.2) for symptomatic VTE recurrence which was independently adjudicated with reference to baseline imaging.

Results

There was no significant association between Lp(a) as a continuous variable and recurrent VTE nor in gender stratified subgroups. No statistically significant differences were observed in the median Lp(a) concentrations between patients who recurred and those who did not recur (median (interquartile range): 0.09 g/L (0.17) versus 0.06 g/L (0.11) respectively; p = 0.15). The Lp(a) cut-off point of 0.3 g/L was not significantly associated with recurrent VTE for the overall population nor in gender stratified subgroups.

Conclusions

Elevated serum Lp(a) does not appear to be associated with recurrent VTE in patients with history of first unprovoked VTE and may not play a role in identifying patients with unprovoked VTE at high risk of recurrence. There was no optimal predictive threshold for the overall population or for sex sub-groups and Lp(a) ≥ 0.3 g/L was not a significant predictor of recurrent VTE.     

Venous thromboembolism in children with cancer – A population-based cohort study

Introduction

Cancer is a known risk factor for venous thromboembolism (VTE) in adults, but population-based data in children are scarce.

Materials and methods

We conducted a cohort study utilising linkage of the Clinical Practice Research Database (primary care), Hospital Episodes Statistics (secondary care), UK Cancer Registry data and Office for National Statistics cause of death data. From these databases, we selected 498 children with cancer diagnosed between 1997 and 2006 and 20,810 controls without cancer. We calculated VTE incidence rates in children with cancer vs. controls, and hazard ratios (HRs) using Cox regression.

Results

We identified four VTE events in children with cancer compared with four events in the larger control population corresponding to absolute risks of 1.52 and 0.06 per 1000 person-years respectively. The four children with VTE and cancer were diagnosed with hematological, bone or non-specified cancer. Childhood cancer was hence associated with a highly increased risk of VTE (HR adjusted for age and sex: 28.3; 95%CI = 7.0-114.5).

Conclusions

Children with cancer are at increased relative risk of VTE compared to those without cancer. Physicians could consider thromboprophylaxis in children with cancer to reduce their excess risk of VTE however the absolute risk is extremely small and the benefit gained therefore would need to be balanced against the risk invoked of implementing such a strategy.

Novelty & Impact Statements

While there is a reasonable level of knowledge about the risk of VTE in adult populations, it is not well known whether this risk is reflected in paediatric patients. We found a substantial increase in risk of VTE in children with cancer compared to a child population without cancer. While this finding is important, the absolute risk of VTE is still low and must be balanced with the risks of anticoagulation.