Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial

Abstract

Aims: To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life.

Methods: We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life.

Results: The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31-0.63) compared with sham (-0.16; 95% CI - 0.33-0.02) yielding a net treatment increase of 0.63 (95% CI 0.37-0.89; P < 0.001 between groups). Improvements with apheresis compared with sham also occurred in atherosclerotic burden as assessed by total carotid wall volume (P < 0.001), exercise capacity by the 6 min walk test (P = 0.001), 4 of 5 domains of the Seattle angina questionnaire (all P < 0.02) and quality of life physical component summary by the short form 36 survey (P = 0.001).

Conclusion: Lipoprotein apheresis may represent an effective novel treatment for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms.

Keywords: Apheresis; Cardiovascular magnetic resonance; Lipoprotein(a); Myocardial perfusion; Refractory angina.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Consort diagram.

Figure 2

Quantitative CMR perfusion pixel maps pre and post apheresis and pre and post sham (A) and group data from myocardial perfusion at rest (left), perfusion with stress (middle) and the myocardial perfusion reserve (right) (B). (A) Quantitative CMR perfusion pixel maps pre- and post-apheresis and pre- and post-sham. The colour scale shows perfusion from 0–4 mL/g/min as low (black-green), medium (mauve-pink) and high (orange-white), therefore brighter colours represent greater perfusion. In this single patient example, there is clear improvement in stress perfusion after apheresis compared with baseline, but no change is seen during sham treatment. (B) Group data are shown from myocardial perfusion at rest (left), perfusion with stress (middle) and the myocardial perfusion reserve (right). There are no changes in rest perfusion with apheresis or sham, but stress perfusion increases significantly with apheresis compared with sham. The myocardial perfusion reserve increases with apheresis because of the improved stress perfusion.

Figure 3

Improvements during apheresis compared with sham. Graphs showing improvements during apheresis compared with sham in: distance walked on 6 min walk test (top left); angina (top right); physical limitation (bottom left); overall physical wellbeing (bottom right).

Figure 4

Summary illustration of the trial design and the key findings.