Marc Giménez-Milà MD
Anaesthesiologists working in critical care units, operating theatres and other areas such as gastrointestinal endoscopy and bronchoscopy have relied on newly published scientific material to approach patients suffering from COVID-19. Various safety measures, diagnostic methods and pharmacological treatments have been reported throughout the pandemic period with different and contradictory messages as more knowledge of the disease was gathered. I must confess my temptation to review, contextualise and summarise the abundant amount of articles about COVID-19 in perioperative medicine published in the last 3 months; assuming the risk of
resembling Dr Indiana Jones’ tireless search for the Holy Grail which would nowadays represent the cure of a new and deadly disease.
I am also determined to learn about the wider non-COVID population and that is why I came across with the interesting and very well executed work “Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery”(1). CM Samama et al performed an international, double-blinded and non-inferior randomised controlled trial comparing the Anti-Xa rivaroxaban with the low molecular heparin weight enoxaparin as pharmacological thromboprophylaxis. The researchers in the PRONOMOS trial randomised a total of 3604 adult patients, 1809 to receive rivaroxaban and 1795 enoxaparin for more than 2 weeks after minor surgical orthopaedic surgery of lower limb (Achilles’ repair, knee (including unicompartmental knee prosthesis), tibial plateau, etc). Exclusion criteria were pregnancy, bodyweight less than 50 or over 120 kg, concomitant treatment with vitamin K antagonists, clopidogrel, ticagrelor or prasugrel. Renal failure with calculated creatinine clearance < 30mL/min and liver failure with Prothrombin time <60% were also exclusion criteria.
The primary efficacy outcome was the development of a major venous thromboembolic event such as symptomatic distal or proximal deep-vein thrombosis, asymptomatic deep vein thrombosis, pulmonary embolism or venous thromboembolism–related death during the treatment period. Compression ultrasonography was performed between 15 days and 3 months after randomisation to diagnose asymptomatic vein thrombosis and a telephone conversation was held at day 30 of end of treatment to rule out thrombotic events. Secondary outcomes were major and minor bleeding events.
The authors reported major venous thromboembolism in 4 out of 1661 (0.2%) in the rivaroxaban group and in 18 out of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputations, 0.25; 95% confidence interval, 0.09 to 0.75) with statistical significance both in non-inferiority and superiority analysis (p<0.001 and p=0.001 respectively). Secondary variables did not differ between groups with 1.1% and 1% of the incidence of major or non-major clinically relevant bleeding in the rivaroxaban and enoxaparin groups, respectively.
These results must be related to the 4 phase III trials showing the benefit of rivaroxaban compared with enoxaparin after total hip and knee replacement (2,3). A total of 12729 patients were included and symptomatic VTE and all-cause mortality occurred in 29/6183 patients receiving rivaroxaban (0.5%) versus 60/6200 patients receiving enoxaparin (1.0%; p=0.001). A non-significant increase in bleeding events was found in the rivaroxaban group.
Oral administration may be a more favourable administration route than subcutaneous, especially for patients with visual or motor disabilities and should be chosen whenever possible.
Like most randomised trials, inclusion and exclusion criteria may impact with translation into real-life clinical practice. We will need more time to know the benefit of rivaroxaban on elderly patients, with liver and renal compromise and taking other antiagregant drugs than aspirin.
We are thankful to authors for provision of this relevant and reliable piece of knowledge on how to prevent venous thromboembolic complications after lower limb minor orthopaedic procedures. A COVID-free research paper is mostly commendable during these times, Thank you PRONOMOS!!!
- Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery. Samama CM, Laporte S, Rosencher N, Girard P, Llau J, Mouret P, et al. N Engl J Med. 2020 May 14;382(20):1916-1925.
- Turpie AGG, Lassen MR, Eriksson BI, et al.. Thromb Haemost 2011;105:444-53.
- European Medicines Agency. Sum- mary of product characteristics: Xarelto (rivaroxaban). 2018 (https://www.ema .europa.eu/en/documents/product-information/xarelto-epar-product -information_en.pdf ).
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