Switching from LDL Apheresis to PCSK9 Inhibitor: Effects on Lipids, Quality of Life

Cholesterol bloodstream
Cholesterol bloodstream
An undesirable lipoprotein effect of LDL apheresis is the lowering of high-density lipoprotein (HDL) cholesterol.

Low-density lipoprotein (LDL) cholesterol apheresis is an effective treatment in lowering LDL cholesterol, improving clinical endpoints, and lowering lipoprotein(a) [Lp(a)] in patients with heterozygous familial hypercholesterolemia (FH) who cannot tolerate statins, due to unacceptable side effects (eg, muscle pain).1,2 However, an undesirable lipoprotein effect of LDL apheresis is the lowering of high-density lipoprotein (HDL) cholesterol.1 Moreover, apheresis is invasive and time consuming, with resulting compromise of quality of life (QOL).3 Apheresis is also expensive, with “substantial annual costs” representing a “barrier to optimal treatment of FH.”4

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been found to be an effective way of reducing LDL cholesterol and Lp(a) and are used in several settings — eg, when statin therapy is ineffective or if it is not tolerable. Their mechanism of action is to increase LDL receptor function via decreased degradation. Evolocumab and alirocumab, both monoclonal antibodies, are approved and available PCSK9 inhibitors, and both have been found to be effective and well tolerated.3

A recent study conducted by Lappegård et al3 explores lipid profiles and QOL in three patients with heterozygous FH and coronary heart disease, who had already been established in long-term weekly apheresis for 135 ± 13(SD) months. Subjects were transitioning to bi-weekly subcutaneous evolocumab. The patients began taking evolocumab and blood samples were analyzed before and after the last LDL apheresis (week 0) treatment, and immediately before evolocumab administration (week 1), and then biweekly before administration of evolocumab (weeks 3, 5, and 7). QOL was assessed at weeks 1, 3, and 7, using the standardized EuroQol questionnaire (EQ-5D-3L).

The researchers chose a seven-week protocol because several studies have demonstrated that most LDL reduction is obtained by week 4 of treatment with PCSK9 inhibitors.5-7 They felt it was “reasonable to assume” that in their study, maximum effect of evolocumab would be achieved at week 7.

Prior to the final LDL apheresis, the highest untreated LDL level was 10.3 ± 0.8 mmol/L, 5.5 ± 0.9 mmol/L pre-apheresis and 1.2 ± 0.2 mmol/L post-apheresis (p = 0.02). One week after apheresis, the LDL level was 6.1 ± 0.7 mmol/L. After three (bi-weekly) injections of evolocumab, LDL-C was 5.0 ± 0.7 (P < 0.001).