POT-KAST and POT-CAST: Questioning Routine Thromboprophylaxis After Casting or Knee Surgery

The value of prescribing thromboprophylaxis to prevent venous thromboembolism (VTE) after knee arthroscopy or casting of the lower leg is debatable, and the risk−benefit ratio has not been well established.

In a study published in the New England Journal of Medicine, Raymond A. van Adrichem, MD, from the Leiden University Medical Center in the Netherlands, and co-authors provided evidence that prophylaxis with low-molecular-weight heparin (LMWH) was not effective for preventing symptomatic VTE, compared with placebo, and that it may be unnecessary in these patients.

“Routine anticoagulant prophylaxis for patients with lower-leg plaster cast or knee arthroscopy is not recommended, as it was found not to be effective,” co-author Suzanne Cannegieter, MD, PhD, also from Leiden University Medical Center, told ASH Clinical News. “This large patient population will not need to be exposed to the burden and risks of anticoagulant therapy anymore.”

Dr. van Adrichem and co-authors conducted two parallel, multicenter, randomized, controlled, open-label trials at 10 hospitals in the Netherlands: POT-KAST (Prevention of Thrombosis After Knee Arthroscopy) and POT-CAST (Prevention of Thrombosis After Lower Leg Plaster Cast).

In each trial, patients were randomized 1:1 to receive LMWH (nadroparin or dalteparin administered subcutaneously) or no anticoagulant therapy (control group). Patients were excluded if they had a history of VTE, had a contraindication to LMWH, were pregnant, or were receiving anticoagulant therapy for other indications (although use of antiplatelet drugs was allowed).

Patients were followed for three months “because, after this period, the risk of VTE returns to baseline,” the authors explained. Follow-up consisted of telephone interviews during which patients were asked whether they had undergone examination for a suspected VTE, visited the hospital, and adhered to the treatment program. The patient’s general practitioner was contacted for this information if the patient did not respond.

POT-KAST

POT-KAST included adult patients (mean age = 48.5±12.5 years) who were scheduled to undergo knee arthroscopy for meniscectomy, diagnostic arthroscopy, removal of loose bodies, or other indications. Between May 2012 and January 2016, 1,543 patients were randomized, of whom 1,451 were included in the intention-to-treat population: 731 LMWH-treated patients and 720 controls. LMWH was administered once daily for the eight days following arthroscopy, with the first dose administered post-operatively, but before discharge, on the day of surgery.

VTE was suspected in 12 patients and confirmed in five (0.7%) in the treatment group (4 cases of deep vein thrombosis [DVT] and 1 case of pulmonary embolism [PE]), while researchers observed 11 suspected cases and three confirmed cases (0.4%) of VTE (2 DVTs and 1 PE) in the control group. The relative risk (RR) for VTE was 1.6 (95% CI 0.4-6.8), with an absolute difference in risk of 0.3 percentage points (95% CI -0.6 to 1.2).

Major bleeding occurred in one patient (0.1%) in each group: hemarthrosis of the knee in the treatment cohort and surgical-site bleeding in the control group (absolute difference of risk = 0; 95% CI -0.6 to -0.7). Minor bleeding occurred in 69 patients (9.5%) in the LMWH cohort and 39 patients (5.4%) in the placebo cohort. No patient deaths were reported.

POT-CAST

POT-CAST included adult patients (mean age = 46±16.5 years) who presented to the emergency department (ED) and were treated for at least one week with lower-leg casting. Between March 2012 and January 2016, 1,519 patients were randomized, of whom 1,435 were included in the intention-to-treat population: 719 LMWH-treated patients and 716 controls. LMWH was administered for the full period of immobilization, with the first dose administered in the ED.

Ten patients in the treatment group experienced VTE (1.4%; 6 DVTs, 3 PEs, and 1 DVT+PE), compared with 13 patients in the control group (1.8%; 8 DVTs, 4 PEs, and 1 DVT+PE). The RR for VTE was 0.8 (95% CI 0.3-1.7), with an absolute difference in risk of -0.4 percentage points (95% CI -1.8 to 1.0). Two patients (one in each group) also had a distal, superficial VTE.

No patients experienced major bleeding in either cohort, although one clinically relevant non-major bleeding event occurred in one LMWH-treated patient (0.1%). Rates of minor bleeding were also similar: 55 LMWH-treated patients (7.6%) and 49 control patients (6.8%). One patient in the control group died.

In both the POT-KAST and POT-CAST trials, the most common adverse event was infection.

The results of the POT-KAST and POT-CAST trials appear to contradict previous meta-analyses of randomized, controlled trials that suggested anticoagulation therapy reduced the risk of VTE in both settings, but Dr. van Adrichem and co-authors noted that those trials were conducted with stricter exclusion criteria and therefore limit generalizability. “A strength of our trials was the pragmatic design, with conditions set to approximate general clinical practice as much as possible,” they wrote.

“In light of the high frequency of knee arthroscopy and casting worldwide, a considerable number of cases of VTE will nevertheless occur, and any possible prevention of these events should still be pursued,” the researchers concluded, noting that a higher dose or longer duration of treatment may be suitable only for patients at the highest risk of developing VTE.

“It can be hypothesized that patients who have symptomatic VTE treatment have a high baseline risk and that casting or knee arthroscopy is a relatively small trigger that, when added to the baseline risk, leads to thrombosis,” they continued. “We speculate that, for the patients at the highest risk, the routine prophylactic dose is insufficient.”

The studies were limited by the non-blinded trial design. In addition, the lack of effect of anticoagulation could have been related to the dose, type, or duration of treatment.


Reference

van Adrichem RA, Nemeth B, Algra A, et al. Thromboprophylaxis after knee arthroscopy and lower-leg casting. N Engl J Med. 2017;376:515-25.

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