Cholesterol

Assessing opinion on lower LDL-cholesterol lowering, and the role of newer lipid-reducing treatment options (2023)

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Type of publication:
Journal article

Author(s):
Connolly, Derek L; Zaman, Azfar; *Capps, Nigel E; Bain, Steve C; Fernando, Kevin.

Citation:
British Journal of Cardiology. 30(2):14, 2023.

Abstract:
While statins are the gold standard for lipid-lowering therapies, newer therapies, such as PCSK9 inhibitors, have also demonstrated low-density lipoprotein cholesterol (LDL-C) reduction, but with a similar or better
safety profile. Conflicting guidance has contributed to a low uptake. More up-to-date, evidence-led guidance supports greater use of newer therapies, particularly in combination with statins, to reduce LDL-C to levels shown to be effective in trials. The aim of this study was to determine how such guidance can be implemented more effectively in the UK. Using a modified Delphi approach, a panel of healthcare professionals with an interest in the management of dyslipidaemia developed 27 statements across four key themes. These were used to form an online survey that was distributed to healthcare professionals working in cardiovascular care across the UK. Stopping criteria included 100 responses received, a seven-month window for response (September 2021 to March 2022), and 90% of statements passing the predefined consensus threshold of 75%. A total of 109 responses were analysed with 23 statements achieving consensus (four statements <75%). Variance was observed across respondent role, and by UK region. From the high degree of consensus, seven recommendations were established as to how evidence-based guidance can be delivered, including a call for personalised therapy strategies and simplification of LDL-C goals, which should be achieved within as short a time as possible.

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Impact of PCSK9 inhibitors Alirocumab and Evolocumab on total & LDL cholesterol in clinical practice (2017)

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Type of publication:
Conference abstract

Author(s):
*Capps N.

Citation:
Atherosclerosis Supplements; 2017; vol. 28, e13

Abstract:
Background: The PCSK9 inhibitors Alirocumab (Al) and Evolocumab (Ev) were recently recommended for use in the NHS on the basis of NICE TA393 and 394 respectively. Clinical trials of both drugs show rapid, significant and continued reductions in total (TC) and LDL cholesterol (LDLC), however confirmation of their efficacy in UK clinical practice is required. Methods: The first patients in the hospital lipid clinic treated with Al 75 mg (14) or Ev 140 mg (13), with pre and post initiation (after 2-3 injections) fasting bloods, were evaluated. All results are in mmol/L. Results: 19 patients had Familial Hypercholesterolaemia, 9 classed by NICE as high or very high risk. Of the remaining 8 patients 5 were HR and 3 VHR. Overall mean TC and LDLC fell from 7.83 to 5.04 and 5.8 to 3.0, ie by 36 and 48%. For Alirocumab 75 mg mean TC and LDLC fell from 8.21 to 5.71 and 6.20 to 3.48, ie by 30 and 44%; individual reductions were 10 to 45% for TC and 13 to 62% for LDLC. For Evolocumab 140 mg mean TC and LDLC fell from 7.41 to 4.32 and 5.33 to 2.44, reductions of 42 and 54%; individual reductions were 32 to 55% for TC and 45 to 69% for LDLC. LDLC fell below 2.0 in 6 patients (Al 1, Ev 5), the lowest to 1.4 mmol/L. Conclusions: The data confirm the rapid and significant reductions in TC and LDLC with Al and Ev in previously difficult to treat patients, however many still had LDLC higher than ideal. This cohort did not contain patients treated with 150 mg Al, or by both drugs, so a direct comparison is not reported.

HEART UK statement on the management of homozygous familialhypercholesterolaemia in the United Kingdom (2016)

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Type of publication:
Journal article

Author(s):
France M., Rees A., Datta D., Thompson G., *Capps N., Ferns G., Ramaswami U., Seed M., Neely D., Cramb R., Shoulders C., Barbir M., Pottle A., Eatough R., Martin S., Bayly G., Simpson B., Halcox J., Edwards R., Main L., Payne J., Soran H.

Citation:
Atherosclerosis, December 2016, vol./is. 255/(128-139)

Abstract:
This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.