Case-fatality of recurrent venous thromboembolism and major bleeding associated with aspirin, warfarin, and direct oral anticoagulants for secondary prevention

Wu, Cynthia; Alotaibi, Ghazi; Alsaleh, Khalid; Linkins, Lori‐Ann; McMurtry, M. Sean

doi:10.1016/j.thromres.2014.10.033

Cited by 41 publications

(27 citation statements)

References 36 publications

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“…A number of studies have already shown that GI bleeds attributable to aspirin carry a risk of death that is lower than that of spontaneous GI bleeding. [7,25–28]. …”

Section: Introductionmentioning

confidence: 99%

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

et al. 2016

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BackgroundAspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin.MethodsIn a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin.ResultsEleven randomised trials were identified in the literature search. In these the relative risk (RR) of ‘major’ incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43).ConclusionsThe majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.

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“…A number of studies have already shown that GI bleeds attributable to aspirin carry a risk of death that is lower than that of spontaneous GI bleeding. [7,25–28]. …”

Section: Introductionmentioning

confidence: 99%

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

et al. 2016

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“…As already assessed in the main trials with DOAC, a low incidence of fatal bleeding was confi rmed in all the extension trials. In a recent meta-analysis evaluating the case-fatality rate of VTE recurrences and major bleeding during an extended antithrombotic treatment with aspirin, warfarin or DOAC, a lower composite outcome of fatal recurrent VTE and fatal bleeding when compared with placebo was observed only with the DOAC, thus suggesting that the benefi t of an extended anticoagulation outweighs the bleeding risk in a large number of patients [57].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

Elmi

Pasquale

Pesavento

2017

Vasa

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Summary: As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefi nite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a fi rst unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profi le has recently been strengthened with systematic reviews and metaanalyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to signifi cantly decrease the risk of recurrences with an excellent safety profi le. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.Keywords: Venous thromboembolism, anticoagulation, thrombophilia, recurrence, major bleeding, fatal bleeding especially common after unprovoked VTE episodes; although the highest risk of recurrence is observed in the fi rst six months following the acute event, it remains quite relevant for a longer time. The cumulative ten-year incidence of recurrences after anticoagulant withdrawal approaches 40 % among all patients with VTE, reaching 52.6 % in unprovoked VTE and 22.5 % in provoked VTE. Patients with VTE provoked by a medical reversible risk factor are more likely to develop recurrences than patients with recent trauma or surgery (cumulative ten-year incidence of recurrences 31.8 % vs 11.4 % respectively) [3]. Moreover, a catch-up phenomenon regarding the late recurrences in the course of VTE has been demonstrated, as diff erent duration of anticoagulant therapy fail to decrease their incidence, once the anticoagulant drug has been withdrawn [4,5].Among the other late complications, PTS develops in up to 50 % of patients previously aff ected by DVT and sometimes leads to a devastating and chronic disease, characterised by leg swelling and venous ulcers.CTEPH is a rarer, but potentially fatal complication of VTE and develops in a variable rate of subjects, ranging

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“…En los ensayos clínicos de tratamiento anticoagulante prolongado con duración superior a tres meses, el porcentaje de pacientes con ETV no provocada es muy elevado, entre el 70% y el 93%. Sin embargo al analizar las edades, nos encontramos en la misma situación de los ensayos de tratamiento inferior a 3 meses: la mayoría de los pacientes incluidos en dichos ensayos, no se pueden considerar ancianos; la media de edad oscila entre los 55 y los 58 años [37][38][39][40] . Los estudios RE-SONATE (con dabigatran), EINSTEIN-EXT (con rivaroxaban), y AMPLIFY-EXT (con apixaban), comparan AOAD frente placebo; sólo en el RE-MEDY, existe una comparación de dabigatran frente tratamiento convencional.…”

Section: Anticoagulantes Orales De Acción Directa: Experiencia En Ancunclassified

“…Los estudios RE-SONATE (con dabigatran), EINSTEIN-EXT (con rivaroxaban), y AMPLIFY-EXT (con apixaban), comparan AOAD frente placebo; sólo en el RE-MEDY, existe una comparación de dabigatran frente tratamiento convencional. Los diferentes meta-análisis publicados sobre tratamiento prolongado en ETV donde se comparan diferentes opciones, los AOAD presentan una eficacia igual al tratamiento convencional, con menor porcentaje de sangrados mayores y recurrencias de trombosis [37][38][39][40] . Se documenta el sangrado mayor en 0'56 por 100 pacientes/año (IC: 0'24-1'1) de los tratados con AOAD, frente el 1'6 por 100 pacientes años (IC: 1'2-2'1) de los que reciben tratamiento con AVK.…”

Section: Anticoagulantes Orales De Acción Directa: Experiencia En Ancunclassified

“…Se documenta el sangrado mayor en 0'56 por 100 pacientes/año (IC: 0'24-1'1) de los tratados con AOAD, frente el 1'6 por 100 pacientes años (IC: 1'2-2'1) de los que reciben tratamiento con AVK. No hay evidencia de sangrados fatales en los ensayos clínicos con AOAD, frente un 6'8% de letalidad de los pacientes tratados con AVK 39 . El efecto secundario más temido del tratamiento con AVK son los sangrados.…”

Section: Anticoagulantes Orales De Acción Directa: Experiencia En Ancunclassified

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Controversias sobre la enfermedad tromboembólica venosa no provocada en ancianos

Ríos-Prego¹,

Núñez-Fernández²,

Monreal-Bosch³

2016

Gal. Clin.

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Desde los primeros trabajos epidemiológicos sobre la enfermedad tromboembólica venosa (ETV), que incluye la trombosis venosa profunda (TVP) y la embolia de pulmón (EP), se ha comprobado que tanto la prevalencia como (sobre todo) la incidencia de esta enfermedad aumentan a medida que lo hace la edad de la población estudiada [1][2][3] . La estrecha relación existente entre mayor edad y mayor riesgo de ETV, se repite a lo largo de los años en distintos países (entre los que se incluye el nuestro) con condicionantes poblacionales y socio-sanitarios diferentes 4,5 . Toda una serie de características hacen distinta la ETV en ancianos respecto de poblaciones de menor edad. Las manifestaciones clínicas tanto de la EP como de la TVP son diferentes en jóvenes respecto de ancianos 6,7 . Se confirma una mayor letalidad de la EP en ancianos 8 , alcanzando en este grupo de edad la 2º causa de muerte en algunos estudios de necropsias 9,10 . En relación con el tratamiento anticoagulante mas empleado [ heparina de bajo peso molecular (HBPM) y antivitaminas k (AVK)] se ha comprobado una mayor tendencia a sangrados graves, fatales e intracraneales en ancianos que en jóvenes 11 . Un aspecto que transmite mayor relevancia al tema son las previsiones sobre población que el Instituto Nacional de Estadística proyecta para los próximos años en nuestro país. Se estima que los incrementos poblacionales en el período 2014-2064 en los grupos comprendidos entre los 75 años y mayores de 100 años oscila entre el 45% y el 2650%. En definitiva será en los últimos segmentos de la pirámide poblacional donde se va a registrar un crecimiento más significativo para los próximos años (www.ine.es). Los datos que se esperan para el futuro ya se están confirmando en la actualidad a nivel hospitalario. En un trabajo de Casademont et al., se evidencia un aumento progresivo de los ancianos mayores de 75 años que ingresan en los servicios de Medicina Interna de nuestro país 12 . Se considera la forma no provocada o idiopática de ETV aquella que no presenta relación con: embarazo, puerperio, inmovilidad (médica o de causa osteoarticular sin intervención quirúrgica) cirugía (sobre todo ortopédica), viajes de más de 6 horas de duración), cáncer activo, trombofilia, o tratamiento hormonal 13 . La forma de ETV no provocada en ancianos representa aproximadamente la mitad de todos los casos de ETV. En abril de 2014, del total de 52. 909 pacientes diagnosticados de ETV e incluidos en el Registro Informatizado de Enfermedad Tromboembólica (RIETE), había 12. 104 pacientes con ETV no provocada, de los cuales aproximadamente el 45% eran mayores de 80 años (5. 494) (datos personales no publicados, M. J. Núñez en representación del RIETE) Existen ciertas características que hacen diferente la forma no provocada de las formas secundarias de ETV con independencia de la edad. La primera es que el riesgo de recurrencia no se modifica con una duración de tratamiento anticoagulante superior a 3 meses 14 . La segunda característica es que el riesgo de recurrencia de ETV se incr...

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Case-fatality of recurrent venous thromboembolism and major bleeding associated with aspirin, warfarin, and direct oral anticoagulants for secondary prevention

Cited by 41 publications

References 36 publications

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

Controversias sobre la enfermedad tromboembólica venosa no provocada en ancianos

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