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Slow-release growth factor revascularises myocardium
NEWS Slow-release growth factor revascularises myocardium new form of growth-factor therapy—slow release of basic fibroblast growth factor (bFGF) over 4–6 weeks—is showing promise in patients with viable but ischaemic and ungraftable myocardium who are having cardiac bypass surgery, report Roger Laham, Michael Simons (Harvard Medical School, Boston, MA, USA) and co-workers this week. According to Simons, this is the first double-blind, placebo-controlled trial in the field and “the first study of cardiac [neo]angiogenesis to use basic fibroblast growth factor”. For the study, 24 patients were selected who were undergoing coronary-artery bypass grafting (CABG) but who had an area of viable myocardium supplied by a major coronary artery with advanced disease which could not be vascularised by CABG or percutaneous intervention. In addition to undergoing CABG, the patients received 10 g bFGF, 100 g bFGF, or placebo by means of sustainedrelease heparin-alginate microcapsules implanted in viable but ischaemic and ungraftable myocar-
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dial areas (Circulation 1999; 100: 1865–71). Two operative deaths (one in the control group and one in the lowdose bFGF group) and three Q-wave myocardial infarctions occurred. No treatment-related adverse events were seen and serum bFGF concentrations did not increase. At clinical follow-up (mean 16 months) only three of the 22 surviving patients (all in the placebo group) had symptoms of angina. Two of these patients underwent successful percutaneous revascularisation. Stress nuclear perfusion imaging at baseline and 90 days after CABG in 20 of the 22 surviving patients indicated a worsening of the defect size of the left ventricle in the placebo group (from 20·7% [SD 3·7] to 23·8% [5·7]), no significant change in the low-dose bFGF group, and a significant improvement in the highdose bFGF group (from 19·2% [5·0] to 9·1% [5·9]). In addition, magnetic resonance imaging assessment showed a decrease in the target ischaemic area in a subset of patients given 100 g bFGF.
According to Robert Stewart (University Hospitals of Cleveland, OH, USA), the researchers have achieved two worthwhile goals. First, he says, they have devised a technique—slow release of bFGF—that obviates concerns about this drug affecting sites other than the myocardium. Second, they have confirmed their clinical observations by use of nuclear perfusion imaging. Stewart hopes that the ease of administration and the apparent safety of this mode of therapy will encourage further studies in which the approach is compared with transmyocardial laser revascularisation. Simons adds that as the population ages, the number of patients that cannot be fully revascularised through CABG will increase, making it important to find alternative ways to revascularise the myocardium. A larger study of slow-release bFGF is already underway, says Simon, and his group has just finished a trial in which intracoronary FGF2 has been tested in 320 patients. Khabir Ahmad
Carnitine supplement best for people with severest limps
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ccording to the results of a endothelium, and by decreasing multicentre study, the use of blood viscosity. carnitine supplements to improve Gregorio Brevetti (University walking ability in Federico II, Naples, patients with peripheral Italy) and colleagues arterial disease should gave 162 patients with be targeted to those walking difficulties prowith the severest dispionyl-L-carnitine and abilities because the 166 patients placebo for drug’s efficacy is great12 months. Walking est in this subgroup. ability and quality of life Walking difficulties in was assessed at 1 and patients with peripheral 2 months and then at 2arterial disease are month intervals. often a result of altered In the patients with carnitine metabolism. the poorest initial walkPropionyl-L-carnitine ing ability (maximum has previously been Free to roam again walking distance of less shown to improve functhan 250 m), walking tion in affected limbs by stimulatdistance increased by 98 m in the ing energy production in ischaemic treatment group (n=86) and by muscles, by improving coagulative 54 m in the placebo group (n=87; fibrinolytic homeostasis in vasal p<0·01). For patients who could
THE LANCET • Vol 354 • November 6, 1999
walk more than 250 m at baseline, walking distance improved by 289 m in the treated group and by 242m in the placebo group, a nonsignificant difference (J Am Coll Cardiol 1999; 34: 1618–24). William Hiatt (University of Colorado Health Sciences Center, Denver, CO, USA) welcomes the findings of this large phase III trial of propionyl-L-carnitine in patients with claudication. But, he says, although the conclusions of the trial are “robust”, they are unlikely to make any difference to clinical practice in the USA, since the drug has not yet been approved by the FDA. However, “proprionyl-L-carnitine is available in Europe, and patients there with severe walking difficulties will benefit”, he adds. Kathryn Senior
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dial areas (Circulation 1999; 100: 1865–71). Two operative deaths (one in the control group and one in the lowdose bFGF group) and three Q-wave myocardial infarctions occurred. No treatment-related adverse events were seen and serum bFGF concentrations did not increase. At clinical follow-up (mean 16 months) only three of the 22 surviving patients (all in the placebo group) had symptoms of angina. Two of these patients underwent successful percutaneous revascularisation. Stress nuclear perfusion imaging at baseline and 90 days after CABG in 20 of the 22 surviving patients indicated a worsening of the defect size of the left ventricle in the placebo group (from 20·7% [SD 3·7] to 23·8% [5·7]), no significant change in the low-dose bFGF group, and a significant improvement in the highdose bFGF group (from 19·2% [5·0] to 9·1% [5·9]). In addition, magnetic resonance imaging assessment showed a decrease in the target ischaemic area in a subset of patients given 100 g bFGF.
According to Robert Stewart (University Hospitals of Cleveland, OH, USA), the researchers have achieved two worthwhile goals. First, he says, they have devised a technique—slow release of bFGF—that obviates concerns about this drug affecting sites other than the myocardium. Second, they have confirmed their clinical observations by use of nuclear perfusion imaging. Stewart hopes that the ease of administration and the apparent safety of this mode of therapy will encourage further studies in which the approach is compared with transmyocardial laser revascularisation. Simons adds that as the population ages, the number of patients that cannot be fully revascularised through CABG will increase, making it important to find alternative ways to revascularise the myocardium. A larger study of slow-release bFGF is already underway, says Simon, and his group has just finished a trial in which intracoronary FGF2 has been tested in 320 patients. Khabir Ahmad
Carnitine supplement best for people with severest limps
A
ccording to the results of a endothelium, and by decreasing multicentre study, the use of blood viscosity. carnitine supplements to improve Gregorio Brevetti (University walking ability in Federico II, Naples, patients with peripheral Italy) and colleagues arterial disease should gave 162 patients with be targeted to those walking difficulties prowith the severest dispionyl-L-carnitine and abilities because the 166 patients placebo for drug’s efficacy is great12 months. Walking est in this subgroup. ability and quality of life Walking difficulties in was assessed at 1 and patients with peripheral 2 months and then at 2arterial disease are month intervals. often a result of altered In the patients with carnitine metabolism. the poorest initial walkPropionyl-L-carnitine ing ability (maximum has previously been Free to roam again walking distance of less shown to improve functhan 250 m), walking tion in affected limbs by stimulatdistance increased by 98 m in the ing energy production in ischaemic treatment group (n=86) and by muscles, by improving coagulative 54 m in the placebo group (n=87; fibrinolytic homeostasis in vasal p<0·01). For patients who could
THE LANCET • Vol 354 • November 6, 1999
walk more than 250 m at baseline, walking distance improved by 289 m in the treated group and by 242m in the placebo group, a nonsignificant difference (J Am Coll Cardiol 1999; 34: 1618–24). William Hiatt (University of Colorado Health Sciences Center, Denver, CO, USA) welcomes the findings of this large phase III trial of propionyl-L-carnitine in patients with claudication. But, he says, although the conclusions of the trial are “robust”, they are unlikely to make any difference to clinical practice in the USA, since the drug has not yet been approved by the FDA. However, “proprionyl-L-carnitine is available in Europe, and patients there with severe walking difficulties will benefit”, he adds. Kathryn Senior
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