Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events

Abstract

Background We investigated in a longitudinal, multicenter, cohort study whether combined lipid apheresis and lipid-lowering medication can reduce extremely high levels of lipoprotein(a) (Lp[a]) and thus prevent major adverse coronary events (MACE) more efficaciously than lipid-lowering medication alone.

Methods Eligible patients had coronary artery disease and Lp(a) levels ≥2.14 µmol/l (95th percentile). All patients received lipid-lowering medications alone until maximally tolerated doses were no longer effective, followed by combined lipid apheresis and lipid-lowering medication. The rates of the primary outcome, MACE, were recorded for both periods.

Results A total of 120 patients were included. The mean duration of lipid-lowering therapy alone was 5.6±5.8 years, and that of apheresis was 5.0±3.6 years. Median Lp(a) concentration was reduced from 4.00 µmol/l to 1.07 µmol/l with apheresis treatment (P<0.0001); the corresponding mean annual MACE rate per patient was 1.056 versus 0.144 (P<0.0001).

Conclusions Lowering of Lp(a) levels by apheresis was efficacious and safe, and we recommend this therapy for patients in whom maximally tolerated doses of medication alone have failed to control coronary artery disease-associated events.

Key Points

  • The clinical relevance of lipoprotein(a) to atherothrombotic complications has been a matter of diagnostic and therapeutic controversy

  • Our findings provide evidence that lowering concentrations of lipoprotein(a) significantly reduces the rate of major adverse coronary events

  • Application of lipid apheresis—the only currently available method to drastically reduce lipoprotein(a) levels—safely and efficaciously reduced the frequency of myocardial infarction by 97%, irrespective of LDL cholesterol concentrations before therapy

  • Screening for extremely high lipoprotein(a) elevations in patients with premature atherosclerosis, recurrent MACE, or a positive family history for atherosclerosis might be useful to direct therapy

  • Given the inconvenience of apheresis therapy, our findings highlight the need for development of drugs to effectively lower pathogenic lipoprotein(a) concentrations

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Figure 1: Absolute numbers of major adverse coronary events during lipid-lowering medication alone and during combined lipid-lowering medication and lipid apheresis.
Figure 2: Changes in annual nonfatal MACE rates before and after initiation of lipid apheresis.

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Acknowledgements

We would like to dedicate this article to Kåre Berg. We are indebted to the patients for their trust and our families for their advice, encouragement and support. We appreciate the dedicated help of the colleagues and nurses of the participating apheresis centers.

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Correspondence to Beate R Jaeger.

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The authors declare no competing financial interests.

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The Clinical investigators who participated in the Lipoprotein(a) Study Group are listed in the Supplementary Appendix 1.

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Jaeger, B., Richter, Y., Nagel, D. et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Rev Cardiol 6, 229–239 (2009). https://doi.org/10.1038/ncpcardio1456

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