Dyslipidemia is an important and undertreated cardiovascular risk factor. HMG Co-A reductase inhibitors (statins) are highly efficacious and the clinical trial evidence demonstrating benefit is unsurpassed. Despite this, there remains some knowledge translation gaps in the screening, diagnosis and treatment of dyslipidemia to prevent atherosclerotic disease. Clinicians have relied on clinical practice guidelines from various stakeholder organizations to aid them in decision making. It is widely recognized that a more accessible approach is required for primary care clinicians to optimize risk reduction. Recently, the 2012 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines were published.¹ The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used under the auspices of the CCS. The new guidelines focused on the importance of risk assessment, the use of statins as primary pharmacological therapy and specific recommendations for lifestyle modification. Harmonization with guidelines by other societies as part of the Canadian Cardiovascular Harmonization of National Guidelines Endeavour (C-CHANGE) was adhered to.²

The recent publication of the 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol has sparked strong opinion in the medical literature, creating opportunity to reinforce the importance of this topic. The ACC/AHA guidelines followed a rigorous multi-year process implemented by the NHLBI, culminating in the recent document.³ The guidelines needed to adhere to specific rules with respect to the highest level of evidence from clinical trials and meta-analyses. These new guidelines have incorporated many new features that are substantially different than previous US, Canadian or European publications. The writing group is to be congratulated for proposing substantive changes that aim to treat a larger proportion of the population at risk and simplify the process for the front-line treating clinician. We will review the similarities, differences and implications of the new guidelines compared with the recently published Canadian standards.

What is concordant between the US and Canadian dyslipidemia guidelines?

1. Of the four primary recommendations for treatment in the ACC/AHA guidelines, three parallel the primary recommendations from the CCS group. These include the use of statin based therapy in subjects with a) established atherosclerosis, b) most subjects with diabetes mellitus and c) those with a low density lipoprotein cholesterol (LDL-C) above 190 mg/dl (5 mmol/L) regardless of risk.
2. The use of a risk assessment tool is also stressed importantly in both guidelines. A lipid profile cannot be adequately assessed by a clinician or patient without putting it into the context of the overall cardiovascular risk.
3. Statin based therapy is the cornerstone of pharmacological treatment on a background of lifestyle modification. At the present time, no randomized trials have demonstrated a benefit of additional lipid modulation compared with statins alone.
4. Safety recommendations were put forward in both the US and Canadian guidelines as they apply to statin therapy. We also felt strongly that the small incremental risk of diabetes that occurs with high potency statins should not dissuade their prescription in appropriately identified subjects.
5. The potential utility of surrogate biomarkers of risk for intermediate risk subjects who did not otherwise fit into a statin therapy group was addressed in both guidelines documents. Like the ACC/AHA document we suggested several possible tests including biochemical and imaging modalities.

What is discordant between the US and Canadian dyslipidemia guidelines:

1. The first difference relates to the use of the new Pooled Cohort Equation for global cardiovascular risk assessment. In the Canadian guidelines we recommended the total cardiovascular Framingham risk score with a correction in some with a family history of premature coronary artery disease. The use of the new risk equation has generated some rhetoric as it has not been extensively calibrated as yet.⁴ In addition, it is not clear how it relates to other assessment tools including Framingham. Canada has a very diverse population and we acknowledge that the Framingham risk engine with a predominantly Caucasian derivation is not ideal for many sectors of the Canadian population. There will likely be many publications in the near term that will validate (or not) the new Pooled Cohort Equation. The more important message here is not the difference between the risk assessment tools, but that risk assessment is an essential component of best patient care.
2. The biggest and boldest difference is the recommendation to treat all subjects at intermediate risk (Pooled Cohort Equation above 7.5%) regardless of LDL-C. This has the potential to greatly increase the number of Americans who would be eligible for statin therapy in a primary prevention setting. The evidence is rather strong that even low-intermediate risk subjects will gain a 25-35% relative risk reduction in cardiovascular events with statin therapy.⁵ While the primary panel of the CCS guidelines recognized this fact we retained the recommendation of treating those in the intermediate risk group (Framingham risk score >10%) with an LDL-C above 130 mg/dl (3.5 mmol/L). We felt that this would maintain a conservative number needed to treat. In addition, this level of LDL-C was the inclusion criteria for several clinical trials of statin based therapy.
3. The new ACC/AHA guideline also makes no recommendation for the use of treatment targets in subjects who begin on statin therapy. Essentially, this suggests a treat-and-follow approach. This has some appeal based on ease of practice and it is clear that no randomized trial has been undertaken to target a specific LDL-C goal. The CCS guidelines panel had certainly considered this option but in the end continued with the concept of LDL-C targets for several reasons: a) the epidemiology and indirect evidence from clinical trials meta-regression suggests that lower LDL-C levels result in fewer cardiovascular events; b) coronary regression can be achieved at LDL-C levels or a % LDL-C reduction recommended in the Canadian guidelines; c) measuring levels does provide some metrics around patient compliance; d) it is a framework that people have been comfortable with; e) this leaves the door open for combination therapy that might be useful in subjects with aggressive atherosclerosis or based on ongoing randomized trials of novel agents.
4. A new recommendation in the CCS guidelines was the inclusion of subjects with chronic kidney disease in the "to be treated" category based on the epidemiology and the randomized Study of Heart and Renal Protection (SHARP) study. This was not explicitly mentioned in the US guidelines.

Implications

Our purpose is certainly not to debate the merits of the Canadian dyslipidemia guidelines compared with the new ACC/AHA standard. They are remarkably similar in many respects. Where there are differences the reasons for these choices are clearly articulated. The primary panel on the Canadian guidelines will continue to monitor new clinical evidence as it emerges. Guidelines are simply frameworks to help clinicians make educated decisions with individual patients. A full risk-benefit discussion with the patient will often create clarity about what the optimal approach is. As statin based therapy becomes less expensive, the movement to more widespread treatment is justified, as has been the case for hypertension. The interest in the new dyslipidemia guidelines will allow local programs to convey the importance of a strategy of risk assessment, and dyslipidemia therapy as part of an overall program of cardiovascular risk reduction to patients, clinicians and health care administrators. This can be nothing but good for our patients.

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References

1. Anderson TJ, Gregoire J, Hegele RA, et al. 2012 update of the canadian cardiovascular society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-167.
2. Tobe SW, Stone JA, Brouwers M, et al. Harmonization of guidelines for the prevention and treatment of cardiovascular disease: The C-CHANGE initiative. CMAJ 2011;183:E1135-50.
3. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the american college of cardiology/american heart association task force on practice guidelines. J Am Coll Cardiol 2013.[Epub ahead of print].
4. Ridker PM, Cook NR. Statins: New american guidelines for prevention of cardiovascular disease. Lancet 2013;382:1762-1765.
5. Cholesterol Treatment Trialists'Ctt C. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet 2012.380:581-90.

Keywords: Cardiovascular Diseases, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Oxidoreductases, Risk Assessment

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