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01-12-2009 | Cardiology | Article

Enzyme replacement improves cardiac endpoints in Fabry’s disease patients


Free abstract

MedWire News: Enzyme replacement therapy over a 5-year period reduced cardiac mass and dysfunction as well as decreasing pain and improving quality-of-life measures in patients with Fabry’s disease, according to an observational study of registry data.

The study, published in The Lancet, showed patients with left ventricular hypertrophy (LVH) at baseline had significant reductions in LVH throughout the 5 years and improved myocardial contractility in the first 3 years of treatment with agalsidase alfa.

Fabry’s disease is a rare lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A. Patients commonly suffer renal and cardiovascular disease which is associated with significant premature mortality; cardiovascular complications include LVH and associated diastolic dysfunction, heart failure, and arrhythmias.

Two observational databases, the Fabry Outcome Survey (FOS) and the Fabry Registry, are following the outcomes of patients receiving the enzyme replacement therapy preparations agalsidase alfa and agalsidase beta, respectively.

Here, Atul Mehta (Royal Free Hospital, London, UK) and co-workers report available follow-up data for FOS patients, 692 of whom were receiving agalsidase alfa.

In patients with LVH at baseline, there was a sustained reduction in LV mass (LVM) index, with a reduction from 68.5 g/m2.7 at baseline to 58.4 g/m2.7 at the end of the first year of treatment in 23 patients with available data, and a fall from 71.4 g/m2.7 at baseline to 64.1 g/m2.7 at the end of the fifth year in 32 patients (p<0.05 at each yearly follow-up). Midwall fractional shortening (MFS) was mildly abnormal in these patients at baseline, but improved significantly at 1, 2, and 3 years of follow-up by 2.6% (n=22; p=0.001), 1.9% (n=23; p=0.0176), and 1.7% (n=26; p=0.02), respectively.

In patients without baseline LVH, LVM index and MFS remained normal during the 5 years, although MFS increased significantly at 1 and 2 years, by 2.2% (n=15; p=0.02) and 2.9% (n=16; p=0.011) from baseline, respectively.

Other findings included significant mean yearly declines in estimated glomerular flow rate (GFR) over 5 years of -3.17 ml/min/1.73 m2 in men and -0.89ml/min/1.73 m2 in women.

And average pain on the Brief Pain Inventory score decreased significantly from 3.7 at baseline to 2.5 after 5 years, while quality of life, measured by deviation from normal EuroQol scores, also improved significantly, from -0.24 at baseline to -0.17 after 5 years.

Metha commented: “These long-term ‘real-life’ registry data confirm the hopes raised by short-term clinical trials, commenced over 10 years ago. Enzyme replacement therapy has the potential to prolong quality of life in this often fatal illness.”

Of study limitations highlighted by Mehta and team, including potential selection bias owing to the tendency for inclusion of sicker and more compliant patients in registries, and incomplete and missing data leading to potential misclassification, Ravi Thadhani (Harvard Medical School, Boston, Massachusetts, USA) and colleagues say that the absence of contemporaneous controls is a particular concern. Concomitant treatments for renal and cardiac disease vary over time and across different countries, they point out in an accompanying editorial.

Thadhani and team add: “Enzyme replacement therapy has only been available since 2001 and, thus, duration of exposure might be too short to assess whether this strategy prolongs life.

“Keeping the high cost of this lifelong treatment front and center, we await confirmatory evidence of a reduction of clinical events with an extension of life.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

By Caroline Price

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