In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)

In a previous 52-week trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 months old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alfa at either 20 mg/kg biweekly (n=8) or 40 mg/kg biweekly (n=8), for up to a total of 3 years. These children continued to exhibit the benefits of alglucosidase alfa at the age of 36 months. Cox regression analyses showed that over the entire study period, alglucosidase alfa treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, as compared to an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 mg/kg and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival, and improved cardiomyopathy.

Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid ␣-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort. Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P Ͻ 0.001) and the risk of invasive ventilation by 58% (P ϭ 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid ␣-glucosidase; no patients withdrew from the study because of safety concerns. Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence. Genet Med 2009:11(3):210-219.

Objective: To examine the perception and management of cardiovascular disease (CVD) risk in Australian primary care. Design, setting and participants: The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster‐stratified, cross‐sectional survey of 322 general practitioners. Each GP was asked to collect data on CVD risk factors and their management in 15–20 consecutive patients aged ≥ 55 years who presented between April and June 2008, and to estimate each patient's absolute risk of a cardiovascular event in the next 5 years. Main outcome measures: Estimated 5‐year risk of a cardiovascular event, proportion of patients receiving appropriate treatment. Results: Among 5293 patients, 29% (1548) had established CVD. A further 22% (1145), when categorised according to the 2009 National Vascular Disease Prevention Alliance guideline, to 42% (2211), when categorised according to National Heart Foundation (NHF) 2004 guideline, had a high (≥ 15%) 5‐year risk of a cardiovascular event. Of the 1548 patients with established CVD, 50% were prescribed a combination of a blood pressure (BP)‐lowering medication, a statin and an antiplatelet agent, and 9% were prescribed a BP‐lowering medication and a statin but not an antiplatelet agent. Among high‐risk patients without established CVD, categorised using NHF 2004 adjustments, 34% were prescribed a combination of a BP‐lowering medication and a statin. GPs estimated 60% of patients with established CVD as having a risk of less than 15%. The GPs’ estimates of risk among patients without established CVD agreed with the centrally calculated estimate (according to the NHF 2004 guideline) in 48% of instances (κ = 0.21). Conclusions: These data confirm substantial undertreatment of patients who are at high risk of a cardiovascular event. We recommend that GPs assess absolute risk for older patients and ensure that high‐risk patients receive evidence‐based pharmacotherapy.

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