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Two studies of apheresis: one in refractory angina, one in raised cholesterol

ESC Congress News 2016 - Rome, Italy

Hot Line Session Results

Prevention


One study in a Hot Line session yesterday suggested a new indication for apheresis among patients with refractory angina, while a second raised the possibility that apheresis could be replaced by a PCSK9 inhibitor in patients with familial hypercholesterolaemia.

Apheresis, which is both expensive and time consuming and can only be performed in specialist centres, is generally regarded as a last-resort for patients with persistently elevated LDL. A new study now suggests that it may also have a role to play in removing lipoprotein a (Lpa) in patients with refractory angina.

It is known that around 15% of patients with angina do not respond to available therapies, explained Tina Khan, one of the study investigators from Imperial College, London. ‘Refractory angina is a challenging condition,’ she said, ‘which continues in spite of optimal medical therapy and revascularisation and imposes much burden on patients. There’s a desperate need for new therapeutic options.’

Lpa has been established as an independent cardiovascular risk factor in a multitude of studies, but cannot be effectively lowered with conventional lipid lowering agents. ‘We believe that Lpa contributes to angina by causing endothelial dysfunction through plasma viscosity, and in addition adheres to the intima more aggressively than LDL cholesterol,’ said Khan.

The study randomised 20 patients with refractory angina and Lpa ≥500 mg/L to three months of blinded weekly Lpa apheresis or sham procedures. Results showed that the primary endpoint of myocardial perfusion reserve, measured by cardiovascular magnetic resonance, increased from 1.45 to 1.93 following apheresis, but decreased during sham procedures  by -0.1, yielding a statistically significant increase for the active treatment group (p<0.001). Results also showed significant improvements in secondary endpoints including exercise capacity (measured by the 6 minute walk test), angina symptoms, quality of life and atheroma burden.

‘Despite our small sample size we got a highly significant result for our primary endpoint,’ said Khan. The investigators, she added, had been surprised to find that 60% of the 100 patients with refractory angina screened for the study had Lpa levels ≥500mg/L. ‘With drug therapies now emerging that reduce Lpa, apheresis may not represent the ultimate therapy for these patients. In future we would like to explore whether these new therapies match up to apheresis.’

In the second apheresis study, ODYSSEY ESCAPE, which was published simultaneously in the European Heart Journal, investigators set out to investigate whether alirocumab, a fully human monoclonal antibody that inhibits PCSK9-mediated hepatic catabolism of the LDL receptor, might reduce the need for apheresis.

For the study 62 patients with heterozygous familial hypercholesterolaemia (HeFH) started  out with apheresis,  and were then randomly assigned 2:1 to alirocumab 150 mg subcutaneously every two weeks for 18 weeks (n=41) or placebo (n=21). Until week 6 the apheresis rate was fixed according to an established schedule, then from weeks 7 to 18 the rate was adjusted according to individual LDL response.

In the alirocumab group the per cent change in apheresis between week 1 to 6 and then weeks 7-18 was  -53.7 compared with +1.6 in the placebo group (P<0.0001). Furthermore LDL was reduced by approximately 50% from baseline in the alirocumab group versus a 2% increase in the placebo group.

‘Alirocumab-treated patients had a 75% additional reduction in the standardised rate of apheresis treatments versus placebo-treated patients,’ said study presenter Patrick Moriarty, from University of Kansas Medical Center. ‘Treatment with alirocumab may allow patients with HeFH to terminate or reduce the frequency of lipoprotein apheresis.’

 

Click here to read other scientific highlights in the full edition of the Congress news.