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Title: Clinical outcomes, perfusion and vascular function in patients with refractory angina and raised lipoprotein (a), treated with lipoprotein apheresis
Author: Khan, Tina
ISNI:       0000 0004 6423 5802
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Background: Angina which is refractory to conventional medical therapy and revascularisation is challenging to manage and novel therapeutic options are needed. Raised lipoprotein(a) is common in refractory angina and is an independent cardiovascular risk factor that can be reduced by lipoprotein apheresis. To date there is no randomised controlled data assessing the clinical benefit of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a). Methods: We conducted a randomised controlled trial in 20 patients with refractory angina and raised lipoprotein(a), with three 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 MPR increased by 0.47 [95% CI, 0.31 to 0.63] from 1.45±0.36 to 1.93±0.45 following apheresis, but decreased during sham by -0.16 [95% CI, -0.33 to 0.02] from 1.63±0.43 to 1.47±0.30; yielding a net treatment increase of 0.63 [95% CI 0.37 to 0.89; p < 0.001 between groups]. Median total carotid wall volume (mm3) reduced during apheresis from 2482 [IQR 1910, 2836] before apheresis to 2251 [IQR 1719, 2437] after apheresis, but increased from 2342 [IQR 1997, 2644] pre-sham to 2455 [IQR 2166, 2831] post-sham (p < 0.001 between groups). The Six Minute Walk Test (6MWT) distance(m) improved by a median value of 70.5[IQR 41.5,105.5]; there was no change in the sham arm (P=0.001 between groups). Significant improvements were also demonstrated in 4 of 5 domains of the Seattle Angina Questionnaire (all p < 0.02 between groups) and quality of life physical component summary by the Short Form 36 Survey (p=0.001 between groups). Conclusions: Lipoprotein apheresis is an effective novel treatment option for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms.
Supervisor: Pennell, Dudley Sponsor: National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral