First ESC/EAS guidelines for dyslipidemia

- EAS 2011 Gothenburg, Sweden

The guidelines represent a landmark for these two European Societies and substantially expand on information given in the Fourth Joint Task Force guidelines for cardiovascular disease prevention.¹ The guidelines were presented at the Wednesday Plenary session and discussed at a Post-Congress Satellite.

Professor Alberico Catapano, EAS Chairperson of the Task Force, Professor of Pharmacology, University of Milan and Director of the Center for the Study of Atherosclerosis in Milan, Italy highlighted four key areas:

• Four levels of cardiovascular risk, as defined by SCORE - very high, high, moderate or low CV risk – to be used as a basis for treatment decisions
• New emphasis on the management of low HDL cholesterol and elevated triglycerides, atherogenic dyslipidemia
• According to Professor Marja-Riitta Taskinen, Biomedicum, Helsinki, Finland and a member of the Writing Group: ‘Atherogenic dyslipidemia is the major risk factor in people with type 2 diabetes or metabolic syndrome’
• Information provided on the diagnosis and treatment of genetic dyslipidemias, including familial combined hyperlipidemia (FCH), characterised by high LDL cholesterol, high triglycerides or both, which affects about one in 100 people •

Emphasis on lifestyle as the first key step for management of dyslipidemia, with inclusion of extensive nutritional information.

ESC Chairperson of the Task Force, Professor Zeljko Reiner, Director, University Hospital Center Zagreb, Croatia said that the management of lipids needs to be taken within the broader context of total cardiovascular risk. As for the Fourth Joint Task Force, the guidelines have used the SCORE risk score to categorise cardiovascular risk. HDL cholesterol has been incorporated into the risk charts to show how this variable impacts cardiovascular risk and allow for more accurate estimation of risk. In addition, the guidelines incorporate relative risk charts, of particular value in young or middle-aged individuals, who may have low absolute risk but high relative risk. Total cholesterol is recommended to be used in estimation of total risk using the SCORE system but is not a target.

The first priority in management is LDL cholesterol. While it is recognised the lipids are a continuum, specific targets have been defined according to the SCORE risk categories:

• <1.8 mmol/L (~70 mg/dL) and/or at least 50 percent reduction in levels if this target cannot be reached in very high risk patients
• <2.5 mmol/L (~100 mg/dL) in high risk patients
• <3.0 mmol/L (~115 mg/dL) in moderate risk patients.

‘These should be seen as the goals of therapy and in actuality, represent the upper threshold for values,’ said Professor Virgil Brown, President of the International Atherosclerosis Society, and Chief of Medicine at the Atlanta Veterans’ Affairs Medical Center, Emory University, Atlanta, Georgia.

Non-HDL cholesterol and apolipoprotein B may be alternative targets to LDL cholesterol, especially in patients with type 2 diabetes, metabolic syndrome or combined dyslipidemia. The targets for non-HDL cholesterol are 0.8 mmol/L (~30 mg/dL) higher than the corresponding LDL cholesterol target. For apoB, the targets are <80 mg/dL and <100 mg/dL in patients at very high or high total cardiovascular risk. The guidelines do not provide targets for HDL cholesterol or triglycerides. ‘While the Task Force recognises the importance of these variables as contributors to risk, there is currently insufficient trial evidence to recommend specific targets. These should be regarded as secondary variables for intervention,’ said Professor Guy de Backer, University Hospital Ghent, Ghent, Belgium.

The guidelines place renewed emphasis on the importance of lifestyle, including diet and exercise, in the management of dyslipidemia. ‘The role of nutrition in the prevention of cardiovascular disease and the effect of dietary factors on lipids has been extensively reviewed. Lifestyle is the backbone of treatment and also has relevance from an economic perspective,’ said Professor Gabriele Riccardi, Università degli Studi of Naples ‘Federico II’, Naples, Italy. The guidelines include information on functional foods, and recommend that inclusion of phytosterol-enriched foods (1-2 g/day) in the diet may be considered in individuals with elevated total and LDL cholesterol levels which do not justify the use of cholesterol-lowering drugs.

Secondary causes of dyslipidemia and compliance (if the patient is already on treatment), should be checked before further pharmacotherapeutic intervention. Statins are the treatment of first choice. ‘The guidelines have used a balanced approach in making treatment recommendations, taking into account both efficacy and safety considerations. The clinician should base selection of the statin on the required LDL cholesterol reduction for the patient’s total cardiovascular risk. It is acknowledged that the response to statin is variable; however, uptitration to the highest recommended dose or the highest tolerable dose is recommended to achieve target levels,’ said Professor Taskinen.

‘While data from simvastatin 80 mg were reviewed, this should not be prescribed to patients,’ said Professor Catapano.

From a safety perspective, statins that do not undergo significant hepatic metabolism via cytochrome P450-related enzymes (pravastatin, rosuvastatin or pitavastatin) may be considered in patients receiving concomitant treatment for co-morbidities.

Bile acid sequestrants or nicotinic acid, or a cholesterol absorportion inhibitor, either alone or in combination with bile acid sequestrants or nicotinic acid, can be considered in patients who do not tolerate statins. Statin combination therapy with either a cholesterol absorption inhibitor, bile acid sequestrant or nicotinic acid may be considered if the target level is not reached.

In combined dyslipidemia, especially prevalent in high-risk patients with metabolic syndrome and types 2 diabetes, raising HDL cholesterol and concomitantly lowering triglycerides, on top of LDL cholesterol reduction is relevant. The high cardiovascular risk associated with this dyslipdemic profile has been previously highlighted by the recent EAS Consensus Panel paper on elevated triglyceride-rich lipoproteins and low HDL cholesterol, in which the current evidence base was critically appraised.² The pharmacotherapeutic recommendations made in the EAS Consensus Panel paper and the ESC/EAS guidelines for the management of dyslipidemia are consistent. Combination of statin with nicotinic acid (niacin) or a fibrate can be considered, and if this is not sufficiently effective for lowering triglycerides, omega-3 fatty acids may be considered. ‘Niacin/laropiprant may be useful as the Task Force recognises the tolerability issues, specifically flushing, associated with niacin. Gemfibrozil should be avoided in combination with a statin due to the increased risk for myopathy; the efficacy of fenofibrate in patients with atherogenic dyslipidemia is supported by subgroup analyses from FIELD and ACCORD.’

The guidelines recognise that the management of dyslipidemia may differ in different clinical settings. Guidance has been provided for a number of groups including the elderly, women, children, and patients with diabetes or metabolic syndrome. However, the guidelines also recognise the need for good clinical judgement. ‘The evidence-base in elderly patients is strong, however, co-morbidities need to be considered’ said Professor Olov Wiklund, Sahlgrenska Academy at Gothenburg University, Sweden.

Chronic kidney disease (CKD) is regarded as a coronary artery disease equivalent with LDL cholesterol as the primary target for treatment. Statins are the first line treatment and also have protective effects on the rate of kidney function loss and on proteinuria. Patients with moderate to severe CKD should be considered as very high risk and clinicians should therefore aim to achieve a LDL cholesterol target of <1.8 mmol/L either with statin alone or in combination.

The incorporation of information on the detection and treatment of genetic dyslipidemias is welcome. FCH, characterised by high LDL cholesterol, high triglycerides or both, is common but often missed in clinical practice. ‘The guideline is useful in raising awareness of the prevalence of FCH and the need to diagnose and treat earlier,’ said Professor Catapano.

The issue of fasting versus nonfasting lipid measurement has been addressed in the guidelines. On the basis of current evidence, triglyceride measurement should be fasting, although total cholesterol, apolipoproteins B and A-I, and HDL cholesterol can be determined in nonfasting samples.

Professor Reiner said that implementation of the guidelines is crucial to their success. ‘Table 3 of the guidelines is key. Dietary advice should be adapted to local circumstances. To aid in practical use we are preparing a clinician’s pocket guide as a ready reference.’ An interdisciplinary approach is indicated at the national level to aid implementation of the guidelines.

References

Guideline citations:

Reiner Z, Catapano A, de Backer G et al. ESC/EAS guidelines for the management of dyslipidaemias. The Task Force on the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; doi:10.1093/eurheartj/ehr158 [Epub ahead of print].

Catapano A, Reiner Z, de Backer G et al. ESC/EAS guidelines for the management of dyslipidaemias. The Task Force on the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011; doi:10.1016/j.atherosclerosis.2011.06.012 [Epub ahead of print].

1. Graham I, Atar D, Borch-Johnsen K et al; European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG). European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J 2007;28:2375-2414.

2. Chapman MJ, Ginsberg HN, Amarenco P et al; European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011; 32: 1345-61, doi:10.1093/eurheartj/ehr112.