Highlights from Late Breaking Session 2

Wednesday News from EAS Helsinki 2021 Virtual: 

The Clinical Late Breaking Session highlighted real-world experience of the use of lipid lowering therapy from the HEYMANS study with evolocumab, the DA VINCI Study in Central and Eastern European (CEE) countries and the German Apheresis Registry.

Clinical trials are fundamental to establishing the efficacy and safety of new treatments. Real-world evidence of the use of these agents is just as important but often more limited. This was the focus of the HEYMANS study, an observational, multicentre cohort study in 1896 adults from 12 European countries initiating first-time treatment with the PCSK9 inhibitor evolocumab (1). Data were collected for up to 26 weeks before and up to 30 months after starting evolocumab.

The current report (2) described findings in 801 patients with familial hypercholesterolaemia (FH), predominantly heterozygous FH (n =766, mean age 57.2 years, 57% male), who were followed to July 2020. Almost three-quarters (73%) of heterozygous FH patients had pre-existing cardiovascular disease, and almost half (44%) were not on a statin.  Thus, the majority of these patients met the criteria for very-high-risk of the 2019 European Society of Cardiology (ESC)/EAS dyslipidaemia guidelines (3). One-third of patients were prescribed the combination of high-intensity statin plus ezetimibe.

Among patients with heterozygous FH, low-density lipoprotein cholesterol (LDL-C) levels decreased from 4.3 mmol/L at entry to 1.86 mmol/L at months 22-24, representing more than 50% reduction from entry levels. Importantly, for patients with homozygous FH, while most had a history of cardiovascular disease and comorbidities, 37% were not receiving a statin. For both groups of patients, LDL-C lowering with evolocumab was consistent with that reported in clinical trials with evolocumab (4,5).  In conclusion, these results from the HEYMANS study, representing the largest cohort of FH patients initiating a PCSK9 inhibitor in routine clinical practice, provide important insights into the real-world use of evolocumab. Lead author Professor Kausik Ray (Imperial College London, UK) discusses the implications of these findings:

DA VINCI was a cross-sectional, observational study of patients prescribed lipid lowering therapy for primary or secondary prevention in 18 European countries (6). Due to the timing of the study, there was a unique opportunity to compare LDL-C goal attainment according to 2016 and 2019 ESC/EAS dyslipidaemia guidelines. Overall, the study included 5888 patients (3000 primary and 2888 secondary prevention patients). Consistent with other reports such as EUROASPIRE (7), the study reported low LDL-C goal attainment; overall, 54% of patients achieved their risk-based 2016 goal and 33% their risk-based 2019 goal. Goal attainment was lower for secondary care patients, with only about one in five attaining 2019 LDL-C goal.

This post hoc analysis of the DA VINCI study (8) reported data from 2154 patients enrolled by 6 CEE countries: Czech Republic, Hungary, Poland, Romania, Slovakia, and the Ukraine. Of 1476 subjects on stable lipid lowering therapy, 664 (45%) were in primary prevention and 812 (55%) in secondary prevention. Only one-third of patients were on high-intensity statin and very few received ezetimibe. LDL-C goal attainment based on 2019 ESC/EAS goals for secondary prevention patients was about half that in Northern and Western Europe (13% versus 23% and 22%, respectively). These novel findings highlight how disparity in access to lipid lowering treatment across Europe impacts LDL-C goal attainment. Professor Michal Vrablik (Charles University in Prague, the Czech Republic) discusses these findings:

Lipoprotein apheresis is a very efficient approach for lowering levels of LDL-C, lipoprotein(a) and other apoB containing lipoproteins, although cost and access are major limiting factors. In Germany, lipoprotein apheresis for both elevated LDL-C and lipoprotein(a) is reimbursed by the health care system, and therefore access is more widespread than in the rest of Europe. The German Lipoprotein Apheresis Registry was established in 2011 and now has 7-year follow-up data. The current report (9) relates to data from more than 47,000 treatments in 2055 patients included by 82 German apheresis centres between 2012 and 2020. All patients had an indication of high LDL-C and/or high lipoprotein(a) levels and progressive atherosclerotic cardiovascular disease (ASCVD). Interestingly, the latest data show that the average age of patients referred for apheresis is increasing, with the majority now 60 years or older.

The current analysis investigated the effect of apheresis treatment on major coronary (MACE) and non-coronary (MANCE) events. All patients showed an acute reduction in LDL-C (median 68%) and lipoprotein(a) (median 72%). When compared with the incidence rate 1 and 2 years before starting treatment, MACE were reduced by 78% and MANCE by 61% during the first 2 years of lipoprotein apheresis and remained stable over 3-7 years. In conclusion, these findings show that lipoprotein apheresis reduces the incidence rate of cardiovascular events in patients with high LDL-C and/or high lipoprotein(a) levels, progressive ASCVD, who were receiving maximally tolerated lipid lowering therapy.

There were also interesting insights regarding lipoprotein(a) in patients with mild to moderate aortic valve stenosis from the CALCIFY study, a matched case-control study (10). The findings show no association between high lipoprotein(a) and active calcification suggesting that the valvular calcific burden likely overrides the effect of lipoprotein(a). The presenter Dr Yannick Kaiser (Academic Medical Center, Amsterdam, the Netherlands) queried whether lipoprotein(a) should instead be investigated in ‘pre-calcific’ stages of aortic valve disease in high-risk individuals.  

Find more at the meeting

Other late breaking presentations are available to view here: Sessions archive on-demand: June 02, Late breaking clinical session.

References

  1. Chart Review of Repatha® in Subjects With Hyperlipidaemia (HEYMANS). https://clinicaltrials.gov/ct2/show/NCT02770131
  2. Ray KK, Dhalwani N, Ebenbichler C, et al. Evolocumab use and LDL-C lowering in a cohort of European patients with familial hypercholesterolemia (FH) – results from the HEYMANS study. EAS Helsinki 2021 – Virtual.
  3. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-188.
  4. Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:331-340.
  5. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385:341-50.
  6. Ray KK, Molemans B, Schoonen WM, et al. EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study. Eur J Prev Cardiol 2020:zwaa047.
  7. De Backer G, Jankowski P, Kotseva K, et al. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis 2019;285:135-46.
  8. Vrablik M, et al. Are risk-based LDL-C goals achieved in primary and secondary care in Central and Eastern Europe? Comparison with other Europe regions from the DA VINCI observational study. EAS Helsinki 2021 – Virtual.
  9. Schettler VJ, et al. The German Lipoprotein Apheresis Registry (GLAR) – more than 7 years on. EAS Helsinki 2021 – Virtual.
  10. Kaiser Y, et al. Lipoprotein(a) is not associated with active calcification assessed with 18F-NaF PET/CT in patients with mild to moderate aortic valve stenosis. EAS Helsinki 2021 – Virtual.
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