Glen J. Pearson

2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult

Many developments have occurred since the publication of the widely-used 2009 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines. Here, we present an updated version of the guidelines, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used, per present standards of the CCS. The total cardiovascular disease Framingham Risk Score (FRS), modified for a family history of premature coronary disease, is recommended for risk assessment. Low-density lipoprotein cholesterol remains the primary target of therapy. However, non-high density lipoprotein cholesterol has been added to apolipoprotein B as an alternate target. There is an increased emphasis on treatment of higher risk patients, including those with chronic kidney disease and high risk hypertension. The primary panel has recommended a judicious use of secondary testing for subjects in whom the need for statin therapy is unclear. Expanded information on health behaviours is presented and is the backbone of risk reduction in all subjects. Finally, a systematic approach to statin intolerance is advocated to maximize appropriate use of lipid-lowering therapy. This document presents the recommendations and principal conclusions of this process. Along with associated Supplementary Material that can be accessed online, this document will be part of a program of knowledge translation. The goal is to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dyslipidemia as a fundamental means of reducing global risk in the Canadian population.

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

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.

Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Working Group Consensus Update

The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy. Regarding cognition, the available evidence is not strongly supportive of a major adverse effect of statins. In contrast, the linkage between statin therapy and incident diabetes is more firm. However, this risk is more strongly associated with traditional risk factors for new-onset diabetes than with statin itself and any possible negative effect of new-onset diabetes during statin treatment is far outweighed by the cardiovascular risk reduction benefits. Additional studies are also discussed, which support the principle that systematic statin rechallenge, and lower or intermittent statin dosing strategies are the main methods for dealing with suspected statin intolerance at this time.

Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016)

The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance. Particularly difficult practice situations are reviewed, including management in young and elderly individuals, and in athletes and labourers. Finally, targeted at specialty practitioners, more detailed analyses of specific but more unusual adverse effects ascribed to statins are updated including evidence regarding new-onset diabetes, cognitive dysfunction, cataracts, and the rare but important immune-mediated necrotizing myopathy.

Use of OTC and Herbal Products in Patients with Cardiovascular Disease

BACKGROUND: The use of nonprescription and herbal products by the public is rising, resulting in an increased potential for adverse reactions or drug interactions in cardiac patients. OBJECTIVE: To describe the utilization patterns for nonprescription medications and herbal products in patients with cardiovascular disease across Canada. METHODS: Patients admitted to 8 teaching hospitals during the winter of 1998/1999 were interviewed by a pharmacist using a structured survey instrument. RESULTS: Interviews were conducted with 306 patients (mean age 66 y; 60% men). The majority (74%) had coronary artery disease; however, hypertension, congestive heart failure, and arrhythmias were also common. The most common product categories used were pain relievers (51%), single-entity vitamin/mineral (38%), multivitamin/mineral (23%), antacids (21%), laxatives (17%), and herbals (17%). As compared with western (28%) and central Canada (26%), fewer patients in the Atlantic region (11%) reported daily use of multivitamin/mineral products. Overall, the usage of specific single-entity vitamin/mineral products was most commonly vitamin E (24%), vitamin C (16%), calcium (9%), and B vitamins (8%). Central Canada reported the highest rates (25%) of daily or weekly use of herbal products. The most common herbal products used were garlic (13%), cayenne pepper (2%), and ginseng (2%). More than half of the patients consulted with their pharmacist at least occasionally regarding the use of these products. CONCLUSIONS: Canadian patients with cardiovascular disease commonly report the use of herbal products and vitamins. Allied health professionals need to be aware of the widespread use of these products and their potential for adverse reactions and drug interactions.

A systematic review of the evidence for pharmacist care of patients with dyslipidemia.

To evaluate the effect of pharmacist care on patients with dyslipidemia.

Tolerability of Statin-Fibrate and Statin- Niacin Combination Therapy in Dyslipidemic Patients at High Risk for Cardiovascular Events

Achieving recommended cholesterol and triglyceride targets for the prevention of cardiovascular events is difficult and frequently requires the use of >1 lipid-lowering medication. This study evaluated the tolerability and effectiveness of combination regimens in high-risk dyslipidemic patients resistant to monotherapy. A retrospective chart review of all patients referred to a cardiovascular risk reduction clinic over a 7.5-year period identified 136 patients who received combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30) regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued combination therapy: 11 (8.1%) experienced myalgia with or without elevated creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine kinase elevation. No patient had combination therapy discontinued due to elevated liver enzymes. Medications were stopped in 8 patients for reasons other than reported adverse effects or biochemical abnormalities, and 5 patients were switched to alternate monotherapy. Mean percent change from baseline to treatment with combination therapy for total cholesterol (-35%), low-density lipoprotein cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (-62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%) were all statistically significant (p <0.01). These results demonstrate that combination statin-fibrate and statin-niacin regimens are safe and effective in managing dyslipidemias in most patients at risk for cardiovascular events who are inadequately treated with one of these agents alone.

Long-Term Impact of a Community Pharmacist Intervention on Cholesterol Levels in Patients at High Risk for Cardiovascular Events: Extended Follow-up of the Second Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP-plus)

Study Objective. To determine the effect of a community pharmacist intervention in patients at high risk for coronary heart disease on low‐density lipoprotein cholesterol (LDL) levels 1 year after completion of the Second Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP‐plus).

Supratherapeutic Response to Ezetimibe Administered with Cyclosporine

OBJECTIVE: To report the case of a patient who underwent orthotopic heart transplant (OHT) and demonstrated a supratherapeutic response to ezetimibe when administered with cyclosporine. CASE SUMMARY: Ezetimibe 10 mg/day was added to the lipid-lowering regimen (atorvastatin 40 mg/day) of a 64-year-old male patient after OHT to achieve a target low-density lipoprotein cholesterol (LDL-C) level ≤97 mg/dL, as recommended by national guidelines. After 2 months of ezetimibe, the patients LDL-C level had decreased by 60% to 51 mg/dL. Subsequently, the dose of ezetimibe was reduced to 5 mg/day and, after another 2 months, a repeat lipid panel revealed LDL-C 57 mg/dL. DISCUSSION: Hyperlipidemia is a common problem among heart transplant recipients. Combination therapy using a statin plus ezetimibe appears to be an attractive option to achieve target lipid levels in this population. However, the manufacturer warns that ezetimibe should be administered cautiously in patients concomitantly receiving cyclosporine. Unpublished data suggest a pharmacokinetic interaction between ezetimibe and cyclosporine that results in a significant 2.3- to 12-fold increase in exposure to total ezetimibe. An objective causality assessment in this case revealed that this supratherapeutic LDL-C reduction was probably related to coadministration of ezetimibe and cyclosporine. A potential mechanism to explain this interaction might be an alteration in glucuronidation induced by cyclosporine. CONCLUSIONS: When ezetimibe is prescribed for patients concomitantly receiving cyclosporine, it should be initiated at a lower than recommended dose (≤5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.

Are the ACC/AHA Guidelines on the Treatment of Blood Cholesterol a Game Changer? A Perspective From the Canadian Cardiovascular Society Dyslipidemia Panel

Department of Medicine, University of British Columbia, Vancouver, British Columbia, CanadaReceived for publication January 10, 2014. Accepted January 14, 2014.Corresponding author: Dr Todd J. Anderson, Libin Cardiovascular Institute of Alberta, University of Calgary, 1403-29th St NW, Calgary, Alberta T2N 2T9,Canada. Tel.: þ1-403-944-1033; fax: þ1-403-944-1592.E-mail: todd.anderson@albertahealthservices.caThe disclosure information of the authorsand reviewers isavailable from the CCSonthe following websites: www.ccs.ca and/orwww.ccsguidelineprograms.ca.This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents theconsensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These rec-ommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowingoptimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement isnot intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard toall the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will notnecessarily produce successful outcomes in every case.0828-282X/