Society Guidelines
2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult

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Abstract

Since the publication of the 2012 guidelines new literature has emerged to inform decision-making. The 2016 guidelines primary panel selected a number of clinically relevant questions and has produced updated recommendations, on the basis of important new findings. In subjects with clinical atherosclerosis, abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy is recommended. For all others, there is an emphasis on risk assessment linked to lipid determination to optimize decision-making. We have recommended nonfasting lipid determination as a suitable alternative to fasting levels. Risk assessment and lipid determination should be considered in individuals older than 40 years of age or in those at increased risk regardless of age. Pharmacotherapy is generally not indicated for those at low Framingham Risk Score (FRS; <10%). A wider range of patients are now eligible for statin therapy in the FRS intermediate risk category (10%-19%) and in those with a high FRS (> 20%). Despite the controversy, we continue to advocate for low-density lipoprotein cholesterol targets for subjects who start therapy. Detailed recommendations are also presented for health behaviour modification that is indicated in all subjects. Finally, recommendation for the use of nonstatin medications is provided. Shared decision-making is vital because there are many areas in which clinical trials do not fully inform practice. The guidelines are meant to be a platform for meaningful conversation between patient and care provider so that individual decisions can be made for risk screening, assessment, and treatment.

Résumé

Depuis la publication des lignes directrices de 2012, la nouvelle littérature qui est apparue favorise la prise de décision éclairée. Le principal panel sur les lignes directrices de 2016 a choisi un certain nombre de questions pertinentes sur le plan clinique et a procédé à l’actualisation des recommandations en se basant sur les dernières conclusions importantes. Chez les sujets ayant des signes cliniques d’athérosclérose, un anévrisme de l’aorte abdominale, chez la plupart des sujets atteints d’un diabète ou d’une néphropathie chronique, et chez ceux ayant un cholestérol à lipoprotéines de faible densité ≥ 5 mmol/l, le traitement par statines est recommandé. Pour les autres, l’accent est mis sur l’évaluation des risques liée à la détermination des lipides pour optimiser la prise de décision. Nous avons recommandé la détermination des lipides chez les sujets non à jeun comme alternative convenable à la détermination des concentrations chez les sujets à jeun. L’évaluation des risques et la détermination des lipides devraient être considérées chez les individus de plus de 40 ans ou chez ceux exposés à un risque accru, quel que soit l’âge. La pharmacothérapie n’est généralement pas indiquée chez ceux dont le score de risque de Framingham est faible (SRF; < 10 %). Un plus grand nombre de patients sont maintenant admissibles au traitement par statines, soit ceux de la catégorie de risque intermédiaire du SRF (10 % à 19 %) et ceux de la catégorie de risque élevé du SRF (> 20 %). En dépit de la controverse, nous continuons de préconiser des valeurs cibles du taux de cholestérol à lipoprotéines de faible densité chez les sujets qui commencent le traitement. Nous présentons également des recommandations détaillées sur la modification du comportement en matière de santé indiquée chez tous les sujets. Finalement, nous recommandons l’utilisation de médicaments n’appartenant pas au groupe des statines. La prise de décision partagée est indispensable puisqu’il existe de nombreux domaines dans lesquels les essais cliniques n’éclairent pas pleinement la pratique. Les lignes directrices sont censées servir de plateforme à des échanges significatifs entre le patient et le prestataire de soins de sorte que des décisions individuelles sur le dépistage et l’évaluation des risques, et le traitement puissent être prises.

Section snippets

Introduction and Process

The 2012 Canadian Cardiovascular Society (CCS) dyslipidemia guidelines have been updated to reflect new clinical trial and epidemiologic evidence. The primary panel posed a number of population, intervention, comparator, and outcomes (PICO) questions to create recommendations on the basis of detailed literature review. The PICO format is a common standard used for guidelines implementation, to aid clinicians in determining whether the recommendations apply to their own patients with outcomes

Definitions

CVD events: CV death, nonfatal myocardial infarction (MI), ischemic stroke, revascularization, and acute coronary syndromes hospitalizations.

Number needed to treat (NNT): NNT to prevent 1 CVD event for 5 years of treatment per 1 mmol/L reduction in LDL-C. NNT of < 50 is generally regarded as desirable by physicians with some patients wishing to see NNT < 30 to deem an intervention as acceptable.

Risk Assessment for Primary Prevention

PICO: In adults, does the use of one of the currently recommended risk engines compared with no risk assessment improve the management of dyslipidemia to reduce CVD events?

The primary goals of CVD risk assessment should be: (1) to reassure individuals without any treatable risk factors that they are doing well; (2) to advise individuals with treatable risk factors or unhealthy behaviours; and (3) to identify subjects most likely to benefit from pharmacotherapy. Several studies have also shown

Whom to Consider for Screening

Screening should be considered for men and women older than 40 years of age or at any age with the conditions listed in Figure 1. These conditions are associated with an increased risk of CVD. They represent traditional CVD risk factors and a variety of inflammatory conditions that were reviewed in the 2012 guidelines. In addition, we addressed the following PICO question.

PICO: Among women of any age with previously documented hypertensive diseases of pregnancy should lipid screening be

How to Screen: Fasting or Nonfasting Lipid Determination

PICO: Among adults for whom screening is recommended is nonfasting lipid determination equivalent to fasting lipid determination for risk assessment?

In contrast to changes in triglyceride levels after a large oral fat load, triglyceride and LDL-C levels change relatively little after normal meals in most of the population. General and community-based population studies reported that triglyceride levels increase only 0.2-0.3 mmol/L or 20% after eating normal meals,27, 28 typically peaking 4

Primary and Secondary Lipoprotein Determinants

PICO: In adult patients, are apoB and non-HDL-C still appropriate as alternate targets to evaluate risk?

There is no significant new literature on this topic since the publication of the 2012 guidelines. Non-HDL-C is derived from the simple calculation of total cholesterol minus HDL-C and is the sum of all the cholesterol transported in atherogenic lipoprotein (Fig. 3). One molecule of apoB is present in all atherogenic lipoprotein including LDL, very LDL, remnants, and lipoprotein(a) (Lp(a)).

When to Consider Pharmacological Treatment in Risk Management

PICO: In adults, do current dyslipidemia treatment recommendations on the basis of levels of risk reduce CVD events?

When deciding on whom to consider for pharmacotherapy we suggest the following approach (Fig. 4). (1) For statin-indicated conditions: identify patients who are in the 5 statin-indicated conditions listed in the section on “Statin-indicated Conditions.” Risk assessment is not required for these individuals as statin therapy is indicated. (2) For primary prevention: perform a risk

CKD

PICO: In adults with CKD, who will benefit from statin therapy to reduce CVD events?

Randomized trials have shown benefit of statins or statins combined with ezetimibe in subjects with CKD. This includes subjects with an estimated glomerular filtration rate < 60 mL/min/1.73 m2 and those with preserved estimated glomerular filtration rate in whom CKD is determined on the basis of an increased urinary albumin:creatinine ratio (≥ 3 mg/mmol) for at least a 3-month duration. The Study Heart and Renal

Secondary Testing

PICO: In adults, does the measurement of risk markers improve CV risk assessment in IR subjects to aid in dyslipidemia management?

We recommend limited testing in subjects in whom a clear decision about the use of statin therapy by the patient and clinician is not evident. This would generally be confined to those at low to IR in a primary prevention setting. A full review was not undertaken for all of the potential biomarkers, instead we focused on areas in which new literature was evident. The

Monitoring, Surveillance, and Targets

PICO: In adults who have started pharmacotherapy, does the use of treatment targets reduce CVD events?

We recognize there is controversy regarding the use of lipid treatment targets. There is no conclusive evidence for using targets for lipid-lowering therapy, because no RCTs have tested specific lipid targets. However, we believe that titrating statin therapy to achieve target lipid levels will have beneficial effects on CVD outcomes, particularly for high-risk (statin-indicated conditions)

Health Behaviour Interventions

PICO: In adults with high cholesterol levels and increased CV risk do lifestyle interventions compared with usual care decrease lipid values or CVD events?

Lifestyle interventions remain the cornerstone of chronic disease prevention, including CVD. Data from the INTERHEART study indicate that, in addition to the traditional risk factors (abnormal lipid levels, hypertension, smoking, and diabetes), abdominal obesity, dietary patterns, alcohol consumption, physical inactivity, and psychosocial

Nonstatin Therapy

PICO: In adults already receiving statins, does the combination of other lipid-modulating drugs compared with placebo reduce CVD events?

Potential Adverse Effects of Statins

Statin intolerance and adverse effects remain of great interest in the media and in lay materials readily available to patients. Additionally, this generates many academic publications that have been previously reviewed and synthesized into principles of management that remain applicable. The term, goal-inhibiting statin intolerance, has been advanced to describe this phenomenon.102, 103, 104

Rhabdomyolysis remains very rare with currently marketed statins as previously reviewed. Because myalgia

Practical Approach

The backbone of risk reduction involves a concerted effort to affect lifestyle choices.121 We recognize that there is controversy when it comes to the use of treatment targets. The primary panel continues to believe that monitoring and surveillance of LDL-C levels to achieve consistent target levels or > 50% reduction from baseline will have beneficial effects on outcomes, particularly for high-risk secondary prevention patients. We recognize that several groups have not recommended targets.

Conclusions

The primary panel has tried to capture the recent excitement in the study of dyslipidemia within this document. Although guidelines cannot always reflect the expected changes in dyslipidemia research, we believe that we have added several important recommendations that will move us in that direction. The use of nonfasting lipid determinations will be of great value for patients and service providers. Risk assessment with shared decision-making is meant to recognize that population-based

Acknowledgements

We are grateful to Dr. Kara Nerenberg, Libin Cardiovascular Institute for providing text for the section on hypertensive diseases of pregnancy. We also thank Ms. Marinda Fung for reference editing.

We are very grateful for the thoughtful feedback and comments of the secondary review panel. 2016 Lipids 2nd Panel Members: Ranjani Aiyar MD, Canadian Society of Internal Medicine, Ottawa, Ontario, Canada; Alexis Baass MD, Royal Victoria Hospital, Montréal, Québec, Canada; N. John Bosomworth MD,

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    The disclosure information of the authors and reviewers is available from the CCS on their guidelines library at www.ccs.ca.

    This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.

    These authors contributed equally to this work.

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