A role for lipoprotein apheresis in refractory angina
Lipoprotein apheresis, normally used for lipid control in heterozygous familial hypercholesterolaemia, has shown benefit in patients with refractory angina pectoris and raised lipoprotein(a) [Lp(a)] levels in a small phase III study presented at the European Society of Cardiology (ESC) Congress 2016 held recently in Rome, Italy. [Atheroscler Suppl 2015;18:103-108]
“Refractory angina is a debilitating condition with increasing frequency in Europe and the US. These patients continue to suffer from troublesome symptoms despite optimal medical therapy and revascularization, and available treatment options are limited. There is a pressing need for novel approaches to the treatment of refractory angina,” said lead investigator Dr Tina Khan from the Imperial College London, UK.
High plasma Lp(a) concentration is related to cardiovascular risk, as studies have shown that it promotes atherosclerosis by enhancing intimal deposition of Lp(a) and prothrombotic effects, thus reducing myocardial perfusion (MP). Currently, apheresis is the best available approved treatment for raised Lp(a). Drug therapies are under development, but are not yet widely available. [JAMA 2009;302:412-423; Circulation 2013;128:2567-2576]
“Our study is the first randomized controlled trial to assess the impact of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in the absence of significantly raised LDL-cholesterol,” noted Khan.
In the study, 20 patients with refractory angina and high Lp(a) levels (above 500 mg/L) were randomized to weekly lipoprotein apheresis or placebo (n=10 each) for 3 months, then crossed over after a 1-month washout period. The primary outcome was myocardial perfusion reserve (MPR, the ratio of MP at stress vs MP at rest), measured by cardiac MRI after 3 months of apheresis, compared to baseline.
“We observed a significant increase of 0.63 in MPR with apheresis treatment vs placebo. Specifically, MPR increased from 1.45 to 1.93 with apheresis but did not change significantly with placebo,” reported Khan. “Secondary endpoints of carotid wall volume and distensibility were also improved after apheresis, as were angina symptoms, exercise capacity and quality-of-life scores.”
As for symptoms, patients who received apheresis treatments experienced significant improvements in four out of five domains of the Seattle Angina Questionnaire (SAQ), including in physical limitation score, angina stability score, angina frequency score and quality-of life-score. No such effects were seen in placebo-treated patients.
“Given the demonstrated benefits in MP, carotid atheroma, exercise capacity, angina symptoms and quality of life, apheresis may provide a much needed novel treatment option for this therapeutically challenging patient cohort,” concluded Khan. “Larger trials may help to confirm our findings although they are already backed up by MACE [major adverse cardiovascular event] reduction in observational studies.”
“This study provides evidence of the efficacy of Lp(a) lowering in refractory angina pectoris,” said Dr Peter Libby of the Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, US, who discussed the results. “Ongoing studies should provide more information on the mechanisms driving the benefit of Lp(a) lowering and determine how much of the benefit can be attributed to Lp(a) reduction.”