Low-molecular-weight-heparin versus a coumarin for the prevention of recurrent venous thromboembolism in high- and low-risk patients with active cancer: a post hoc analysis of the CLOT Study.

In patients with active cancer and acute venous thromboembolism (VTE), the low-molecular-weight-heparin (LMWH) dalteparin is more effective than vitamin K antagonist (VKA) in reducing the risk of recurrent venous thromboembolism (rVTE) without increasing the risk of bleeding. However, the relative benefit of LMWH versus VKA in patients with active cancer at high or low risk of rVTE and bleeding is unclear. This post hoc analysis used data from the CLOT study to explore the efficacy and safety of LMWH versus VKA in preventing recurrent thrombosis in high- and low-risk patients with active cancer. High-risk patients were defined by metastatic disease and/or antineoplastic treatment at baseline; low-risk patients presented with neither. Among high-risk patients, rVTE occurred in 25/318 (8%) (LMWH) versus 53/314 (17%) (VKA) (hazard ratio, 0.44; p = 0.001). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 40% (LMWH) versus 41% (VKA). In low-risk patients, 2/20 (10%) (LMWH) had rVTE versus 0/24 (0%) (VKA) (hazard ratio, not estimable; p = 0.998). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 20% (LMWH) versus 29% (VKA). In patients with cancer-associated thrombosis at high risk of rVTE and bleeding, the LMWH dalteparin was more effective than VKA in reducing the risk of rVTE without increasing the risk of bleeding. No difference in rate of rVTE or bleeding was observed between LMWH and VKA among low-risk patients.

Growth Hormone Treatment in Children With Prader-Willi Syndrome: Three Years of Longitudinal Data in Prepubertal Children and Adult Height Data From the KIGS Database.

Context: Longitudinal data of children with Prader-Willi syndrome (PWS) treated with genotropin were registered in the Pfizer International Growth Database (KIGS). Objective: To evaluate efficacy and safety of growth hormone (GH) treatment in a large group of children with PWS. Design: Data registered in KIGS from 1987 to 2012. Setting: Worldwide retrospective cohort study. Patients: Patients included 522 prepubertal children treated with GH for three years and 173 children who had reached adult height. Safety analysis included 2332 children. Intervention involved GH treatment. Main outcome measure: Height standard deviation score (SDS), body mass index (BMI) SDS, occurrence of serious adverse events, and deaths reported in KIGS. Results: In prepubertal children, mean (standard deviation) height SDS improved to -0.31 (1.34) (P < 0.05) during three years of GH treatment. In the adolescent group, height SDS improved until the start of puberty to -0.22 (1.31) (P < 0.05) but had a loss of -0.77 (0.81) during puberty, resulting in a mean adult height SDS of -1.19 (1.37). Total height gain was 0.95 (1.32) SDS. BMI SDS increased in the prepubertal group from 1.11 (2.09) to 1.53 (1.43) (P < 0.05) and did not significantly change in the adolescent group, who had a BMI SDS at an adult height of 1.78 (1.26). KIGS contained 12 death reports. Conclusions: GH treatment in children with PWS significantly improves linear growth. BMI remains on average below +2 SDS, in contrast to the natural course of increasing obesity in PWS. Safety should be closely monitored in children with PWS, with and without GH treatment.

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.

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.

Pregnancy in acromegaly patients treated with pegvisomant.

To summarize all available data on pregnancy outcome of acromegaly patients exposed to the growth hormone receptor antagonist pegvisomant (PEGV) during pregnancy as present in the Pfizer's Global Safety Database. Pfizer's Global Safety Database contains adverse event data obtained from the following sources: spontaneous reports, health authorities, Pfizer-sponsored post-marketing surveillance program (ACROSTUDY), customer engagement programs, and clinical studies, reported regardless of outcome. The safety database was searched up to 10th March 2014. From the 35 pregnancy cases, 27 involved maternal [mean age (range) 33.3 years (23-41) and 8 paternal (33.7 years (32-38)] PEGV exposure. Two female patients were reported with two pregnancy cases each. Fetal outcome was normal in 14 (4 paternal) of the 18 reported as live birth, while 4 cases (1 paternal) did not specify the birth outcome. At conception, PEGV mean dose (range) was 15.3 mg/d (4.3-30). In 3 cases of maternal exposure of the 18 cases reporting live birth, PEGV was continued throughout the pregnancy in a dose of 12.1 mg/d (10-15). In 5 cases (all maternal) an elective termination of the pregnancy was performed with no reported fetal abnormalities, 2 cases (maternal) reported a non-PEGV-related spontaneous abortion and in 1 maternal case an ectopic pregnancy occurred. In 9 cases (3 paternal), the fetal outcome was not reported. Three women reported gestational diabetes; one woman continued PEGV treatment during pregnancy. Although the number of reported pregnancies with exposure to PEGV is very small, the presented data reflect the largest series of data available to date and do not suggest adverse consequences of PEGV on pregnancy outcome. Nevertheless, it should be stressed that PEGV should not be used during pregnancy unless absolutely necessary.