Аспирин предотвращает риск развития рецидива венозного тромбоза

[Dr.Vad]

В недавней НЕЙМовской публикации доктора из Италии представили результаты исследования WARFASA: пациенты с идиопатическим эпизодом венозного тромбоза после проведения стандартного лечения варфарином в течение 6-18 мес. были рандомизированы на 100 мг аспирина или плацебо и наблюдались в течение 2 лет, назначение аспирина снизило риск рецидива тромбоза на 40%: повторный тромбоз случился у 6.6% на аспирине и 11.2% на плацебе в год; (hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93)... большие кровотечения были по 1 в каждой группе и и малых по 3...

N Engl J Med. 2012 May 24;366(21):1959-67.
Aspirin for preventing the recurrence of venous thromboembolism.
Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P; WARFASA Investigators.
Division of Internal and Cardiovascular Medicine and Stroke Unit, Department of Internal Medicine, University of Perugia, Perugia, Italy.

BACKGROUND: About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown.

METHODS: In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome.

RESULTS: Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups.

CONCLUSIONS: Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677).

В редакционном комментарии отмечается, что 35-40% снижение риска тромбоза отмечалось и в предыдущих публикациях, тогда как варфарин снижает риск рецидива тромбоза на 60-90% (но и добавляет риск экстра-кровотечений)...

еще один подобный трайл проводится в Австралии и его результаты будут к концу 2012 - началу 2013 года:

The ongoing Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) study (Australian New Zealand Clinical Trials Registry number, ACTRN012605000004662) has recruited 822 patients with a first unprovoked event, as documented by means of objective testing, who have received warfarin anticoagulant therapy for 3 to 6 months (but not longer than 12 months). Patients have been randomly assigned to either aspirin (100 mg daily) or placebo for a median of 3 years and are being followed for a first occurrence of symptomatic and objectively confirmed deep-vein thrombosis or nonfatal or fatal pulmonary embolism with the use of an intention-to-treat approach. Results of this study are expected during 2012.

[Dr.Vad]

Результаты австралийского трайла опубликованы в Ноябрьском НЕЙМе:

N Engl J Med. 2012 Nov 22;367(21):1979-87.
Low-dose aspirin for preventing recurrent venous thromboembolism.
Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J; ASPIRE Investigators.
Department of Haematology, South Eastern Area Laboratory Services (SEALS), Prince of Wales Hospital, Sydney, Australia.

BACKGROUND: Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism.

METHODS: We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism.

RESULTS: During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P=0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events.

CONCLUSIONS: In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism.

[Dr.Vad]

Анализ исходов по подгруппам на основании вышеприведенных трайлов:

Circulation. 2014 Aug 25.
Aspirin for the Prevention of Recurrent Venous Thromboembolism: The INSPIRE Collaboration.
Simes J, и соавт.

BACKGROUND: -In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The WARFASA and ASPIRE trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups.

METHODS AND RESULTS: -An individual-patient-data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, MI, stroke and CVD death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/year vs 5.1%/year; hazard ratio (HR), 0.68; 95% CI, 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/year vs 5.7%/year; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/year for placebo and 0.5%/year for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients.

CONCLUSIONS: -Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding.

[Dr.Vad]

Ривароксабан 10 мг оказался несколько лучше аспирина и столь же безопасным для профилактики ТГВ, подробнее:

N Engl J Med. 2017 Mar 30;376(13):1211-1222.
Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism.
EINSTEIN CHOICE Investigators.
[Ссылки доступны только зарегистрированным пользователям ]