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Overview

Dr Handrean Soran, the lead author of the guideline and Chair of the HEART UK Medical, Scientific, and Research Committee, stated: ’This expert statement is issued by HEART UK—The Cholesterol Charity, and provides evidence-based consensus recommendations on the safe use of lipid-lowering medications during COVID-19 pandemic and in patients with COVID-19. This guidance offers a consensus view based on available evidence and experts’ opinion.’

This Guidelines summary only covers recommendations most relevant to primary care. For the complete set of recommendations, please see the full guideline.

View this summary online at guidelines.co.uk/455649.article

Visual summary

Algorithm 1: Managing hyperlipidaemia in patients with COVID-19—visual summary

HEART UK algorithm

Reproduced with permission from HEART UK. 

General advice

  • Patients with no symptoms or diagnosis of COVID-19 should continue their lipid-lowering medications, as well as other cardioprotective therapies, as usually prescribed
  • There is no need to withhold lipid-lowering medications during the COVID-19 pandemic—this is especially important in patients who are at high risk of cardiovascular disease, in whom stopping lipid-lowering therapy can increase the risk of an atherosclerotic vascular event.

Recommendation 1

  • Patients treated for hyperlipidaemia should continue with their advised diet and lifestyle measures and should not interrupt their pharmacologic treatment because of the COVID-19 pandemic
  • Lipid-lowering medications can be suspended temporarily in patients with confirmed COVID-19 who are too unwell to receive medications orally
  • Creatine kinase measurements should be considered when clinically indicated and in patients who are critically ill—statin therapy should be stopped if creatine kinase rises 10-fold to levels above 2000 IU/l in asymptomatic patients or at a lower level of fivefold the upper limit of normal in symptomatic patients
  • It is important to reassess and recommence oral lipid-lowering medications in patients who recover before or soon after they leave hospital
  • In rare and inherited disorders such as homozygous familial hypercholesterolaemia (HoFH), heterozygous familial hypercholesterolaemia, or familial chylomicronaemia syndrome (FCS), consult a lipid specialist to assess specific risks and therapeutic challenges (see recommendations 10 and 11).

Abnormal liver functions tests in patients with COVID-19

  • Abnormal liver function tests (LFTs) are increasingly recognised as a feature of COVID-19 infection—it is important to recognise hepatic injury in patients with COVID-19 as the majority of lipid-lowering therapies are metabolised in the liver.

Recommendation 2

  • Continue lipid-lowering therapy in patients with a confirmed diagnosis of COVID-19 and abnormal LFTs unless alanine transaminase (ALT) or aspartate transaminase (AST) rises progressively
  • Stop therapy and monitor if ALT or AST is greater than three times the upper limit of normal
  • Reassess and consider recommencing oral lipid lowering medications in patients who recover before or soon after they leave hospital.

Statins

  • Statins have shown great efficacy in treating a variety of lipid disorders while also providing mortality benefits against cardiovascular disease
  • Pharmacologic blockade of the renin–angiotensin–aldosterone system has been shown to upregulate ACE2 expression in a variety of tissues—this has led some to question the safety of such therapies in patients who test positive for COVID-19.

Recommendation 3

  • Statin therapy should be continued in patients with a confirmed diagnosis of COVID-19, but should be stopped, or the dose reduced, if:
    • ALT or AST rises progressively—stop statin therapy and monitor if ALT or AST is greater than three times the upper limit of normal
    • there is a significant drug–drug interaction identified—consider reducing the dose or change to another statin
    • creatine kinase rises tenfold to 2000 IU/l or more in asymptomatic patients or fivefold the upper limit of normal in symptomatic patients—stop statin therapy
    • there is evidence of myositis—monitor renal function
  • If treatment is suspended, a further individualised risk–benefit assessment should be conducted to restart treatment soon after the patient’s condition has stabilised.

Fibrates

  • Fibrates are used primarily in the treatment of hypertriglyceridaemia—elevated triglyceride levels are used as part of the H-Score, which determines the presence of secondary haemophagocytic lymphohistiocytosis, an under-recognised hypercytokinaemia syndrome thought to occur in COVID-19 infection
  • No drug interactions have been reported between the commonly used fibrates and the proposed drugs on trial for treating COVID-19.

Recommendation 4

  • Fibrate therapy should be continued in patients with and without a confirmed diagnosis of COVID-19 unless:
    • there is a significant drug–drug interaction identified
    • ALT or AST rises progressively—fibrate therapy should be stopped if ALT or AST is greater than three times the upper limit of normal
    • there is clinical and/or biochemical evidence of myopathy or if creatine kinase is greater than five times the upper limit of normal
    • in acute kidney injury with deteriorating estimated glomerular filtration rate
  • Assess drug interactions if oral anticoagulants are initiated
  • If treatment is suspended, further assessment should be conducted to restart treatment soon after the patient’s condition has stabilised.

Ezetimibe

  • Ezetimibe inhibits dietary cholesterol absorption and has been shown to reduce low-density lipoprotein-C (LDL-C) and atherosclerotic cardiovascular disease risk
  • Ezetimibe is considered a safe therapeutic option with few side-effects and no known drug interactions with the proposed medications being trialled for COVID-19.

Recommendation 5

  • Ezetimibe therapy should be continued in patients with confirmed diagnosis of COVID-19 unless:
    • there is a significant drug–drug interaction identified
    • ALT and/or AST rises above three times the upper limit of normal
  • If treatment is suspended, further assessment should be conducted to restart treatment soon after the patient’s condition has stabilised.

Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies reduce cardiovascular events
  • PCSK9 protein is often upregulated during sepsis and inflammation and is postulated to have a detrimental effect on host response and survival—it is unclear whether this translates into an increased susceptibility to respiratory viruses such as COVID-19.

Recommendation 6

  • PCSK9 monoclonal antibodies should be continued in all patients with a confirmed diagnosis of COVID-19
  • In critically ill patients, treatment can be paused until recovery and discharge from the critical care unit
  • If treatment is suspended or delayed, a further individualised risk–benefit assessment should be conducted to restart treatment soon after patient’s condition has stabilised.

Omega-3 fatty acids

  • Eicosapentaenoic acid and docosahexaenoic acid in sufficient amounts reduce triglyceride levels, and are associated with favourable effects on markers of cardiovascular risk such as reduced blood pressure and decreased platelet aggregation
  • There are no significant drug interactions between possible trial therapies for COVID-19 and omega-3 fatty acids; it has been suggested that they may prolong bleeding time, but clinical trials have not shown adverse outcomes in relation to this.

Recommendation 7

  • Omega-3 fatty acids can be continued in patients with a confirmed diagnosis of COVID-19 unless the patient is critically ill
  • If treatment is suspended, a further individualised risk–benefit assessment should be conducted to restart treatment when patient’s condition has improved. 

Bile acid sequestrants

  • Bile acid sequestrants such as cholestyramine, colesevalam, and colestipol interact with bile acids, preventing their absorption in the intestines
  • They do not interact pharmacologically with other agents; however, they may inhibit the absorption of a number of orally administered drugs.

Recommendation 8

  • In the absence of cardiovascular outcome data and given the potential for interfering with drug absorption, it would be reasonable that bile acid sequestrants are discontinued in patients diagnosed with COVID-19.

Nicotinic acid (niacin)

  • Niacin positively impacts apo-B containing lipoproteins and favourably increases apo A1—this translates into reductions in LDL-C and triglycerides while concomitantly raising high-density lipoprotein-C
  • Niacin has been shown to attenuate endotoxaemic lung inflammation in animal models; data in human viral infections are lacking, but no reports questioning its safety profile were published during the previous severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks.

Recommendation 9

  • Niacin therapy can be continued in patients without COVID-19; however, in the absence of consistent clinical trials evidence to support cardiovascular events prevention, niacin should be temporarily discontinued in patients diagnosed with COVID-19.

Homozygous familial hypercholesterolaemia

  • HoFH confers high cardiovascular risk from a very young age—atherosclerotic plaque burden is high and there is particular concern about stopping lipid-lowering therapies.

Recommendation 10

  • Patients with HoFH are at high risk of cardiovascular events and any proposed changes to therapy in these patients should be discussed with a lipid specialist familiar with the management of the condition.

Familial chylomicronaemia syndrome

  • FCS is characterised by very high triglyceride levels and increased risk of acute pancreatitis—the major side-effects of volanesorsen, a newly licensed treatment for FCS, include thrombocytopaenia
  • Emerging evidence suggests that low platelet count is associated with an increased risk of severe disease and mortality in patients with COVID-19. 

Recommendation 11

  • Any proposed changes to therapy in patients with FCS should be discussed with a lipid specialist familiar with the management of the condition.

 

Full guideline:

Iqbal Z, Ho J, Adam S et al; on behalf of HEART UK’s Medical Scientific and Research Committee. Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: an expert panel position statement from HEART UK. HEART UK, 2020. Available at: atherosclerosis-journal.com/article/S0021-9150(20)30504-9/fulltext#%20

All of HEART UK’s Statements of Care (in full) can be accessed by visiting heartuk.org.uk/health-professionals/home.

Published date: September 2020.