title: A post hoc analysis of dalteparin versus oral anticoagulant (VKA) therapy for the prevention of recurrent venous thromboembolism (rVTE) in patients with cancer and renal impairment.
abstract: Venous thromboembolism (VTE) is a common and serious complication in patients with cancer; treatment guidelines recommend extended therapy of ≥6 months with low-molecular-weight heparin (LMWH) for treatment and prevention of recurrent VTE (rVTE) in this population. This post hoc analysis used data from the CLOT study-a phase III, randomized, open-label, controlled study (N = 676)-to compare the efficacy and safety of dalteparin, a LMWH, versus vitamin K antagonist (VKA) for prevention of rVTE in patients with cancer and renal impairment (creatinine clearance <60 ml/min). Overall, 162/676 (24 %) patients had renal impairment at baseline. Patients received subcutaneous dalteparin 200 IU/kg once daily during month 1, followed by 150 IU/kg once daily for months 2-6; or VKA once daily for 6 months, with initial overlapping subcutaneous dalteparin 200 IU/kg once daily for ≥5 days until international normalized ratio was 2.0-3.0 for 2 consecutive days. Endpoints included the rates of rVTE (primary) and bleeding events. Overall, fewer dalteparin-treated patients (2/74 [2.7 %]) experienced ≥1 adjudicated symptomatic rVTE compared with VKA-treated patients (15/88 [17.0 %]; hazard ratio = 0.15 [95 % confidence interval 0.03-0.65]; p = 0.01). Bleeding event rates for both treatments were similar (p = 0.47). In summary, compared with VKA, dalteparin significantly reduced risk of rVTE in patients with cancer and renal impairment (p = 0.01) while exhibiting a comparable safety profile. This analysis supports dosing patients with renal impairment in accordance with patients with normal renal function; however, anti-Xa monitoring could be considered to further support safety in selected patients, particularly those with very severe renal impairment.
authors.affiliation: Pfizer Inc, New York, NY, USA. Seth.Woodruff@Pfizer.com.
authors.forename: Seth
authors.initials: S
authors.lastname: Woodruff
authors.affiliation: Pfizer Inc, Kirkland, QC, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Feugère
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Abreu
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Heissler
authors.affiliation: Pfizer Inc, Kirkland, QC, Canada.
authors.forename: Marcia T
authors.initials: MT
authors.lastname: Ruiz
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Jen
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D017985:Dalteparin / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D054556:Venous Thromboembolism / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D000074:Acenocoumarol; D017985:Dalteparin
keywords: Dalteparin; Low-molecular-weight heparin; Renal impairment; Thromboembolism; Vitamin K antagonist