Arden R. Barry

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.

Omega-3 polyunsaturated fatty acid supplementation in the prevention of cardiovascular disease.

Introduction: Omega-3 polyunsaturated fatty acids (PUFAs) have purported protective cardiovascular (CV) effects. We sought to assess the evidence available for the use of omega-3 PUFAs for the prevention of cardiovascular disease (CVD). Methods: A systematic literature search was conducted using MEDLINE and EMBASE from 1999 to 2015. Placebo-controlled, randomized controlled trials (RCTs) that enrolled over 1000 patients with follow-up greater than 1 year and meta-analyses of RCTs were included. Results: Eight RCTs and 2 meta-analyses were included. In patients with preexisting CVD, only 1 of 5 included RCTs demonstrated a reduction in CV events with omega-3 PUFAs; however, the effect size was minimal, and the study was limited by an open-label design and lack of placebo control. Two meta-analyses concluded omega-3 PUFAs do not reduce CV events in addition to standard, evidence-based therapy in patients after myocardial infarction. Of the 3 predominantly primary prevention RCTs, only 1 demonstrated a minor reduction in major coronary events; however, it was also an open-label study. Furthermore, the safety of omega-3 PUFAs should be considered. While data from RCTs have not demonstrated serious safety concerns, omega-3 PUFAs can increase the risk of bleeding and may interact with other medications that affect hemostasis, such as antiplatelet agents and warfarin. Discussion and Conclusion: There is currently a lack of evidence to support the routine use of omega-3 PUFAs in the primary and secondary prevention of CVD. Pharmacists are ideally situated to engage patients in the discussion of the lack of benefit and possible risk of omega-3 PUFA supplements.

Case report and review of clenbuterol cardiac toxicity

Clenbuterol is an oral β2-agonist utilized as an illicit substance for performance-enhancement or weight loss. We report a case of a 23-year-old male who presented with anxiety and chest tightness after intentional ingestion of 5000 μg of clenbuterol (125 times the recommended adult dose) to lose weight. His electrocardiogram showed sinus tachycardia and diffuse nonspecific repolarization abnormalities with mild inferolateral ST-segment depression. Bloodwork revealed a potassium of 2.0 mmol/L, peak lactate of 9.4 mmol/L, and peak troponin of 5.39 μg/L. A transthoracic echocardiogram was normal except for hyperdynamic left ventricular function. He was treated with intravenous fluids and oral metoprolol. His tachycardia and electrocardiogram abnormalities resolved after 48 h. Clenbuterol has gained notoriety in recent years as a drug of abuse and cases of toxicity will likely continue to increase due to its relative attainability and readily accessible online dosing information. Patients often present with agitation, palpitations, tachycardia, hypokalemia, and hyperglycemia. Treatment is supportive with intravenous fluids, β-blockers, and potassium supplementation. <Learning objective: Clenbuterol, an oral β2-agonist, can be utilized as an illicit substance for performance-enhancement or weight loss. Cardiac toxicity and type II myocardial infarction can occur with clenbuterol overdoses. Associated symptoms include agitation, palpitations, tachycardia, hypokalemia, and hyperglycemia. Treatment is supportive primarily with intravenous fluid, β-blockers, and potassium supplementation.>.

Reasons for non‐use of proven pharmacotherapeutic interventions: systematic review and framework development

RATIONALE, AIMS AND OBJECTIVES The quality of patient care and safety is dependent on addressing both errors of commission (e.g. overuse of medications) and errors of omission (e.g. patients receiving too little care). Despite guidelines recommending the use of certain proven pharmacotherapeutic interventions, a large gap exists between the patients that have an indication for, and those that actually receive such interventions. To address how the rate of implementation of proven interventions can be improved is dependent on a comprehensive knowledge of the factors contributing to their underuse. The aim of the review is to create an evidence-based framework of reasons why eligible patients do not receive proven pharmacotherapeutic interventions. METHODS A systemic review of the published reasons for non-use based on the Cochrane methodology. RESULTS The systematic review identified 67 articles meeting the inclusion criteria. The reasons for non-use were extracted from the studies and a framework was created from the results. CONCLUSIONS The factors associated with lack of implementation of proven pharmacotherapeutic interventions are complex and heterogeneous but can be understood from the perspectives of clinicians, patients and health care delivery systems. Efforts to increase the utilization of proven interventions should focus on disease/intervention-specific programmes that take into account the identified modifiable clinician, patient and system factors.

Short- versus standard-term dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation: A meta-analysis

BACKGROUND Twelve months of dual antiplatelet therapy (DAPT) is recommended after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. However, certain clinical scenarios may require premature discontinuation of therapy (e.g. urgent surgical procedure, major bleeding). The objective of this systematic review and meta-analysis was to investigate clinically relevant outcomes associated with a shorter duration of DAPT after PCI with DES implantation. METHODS A systematic search of Medline and Embase (inception to December 2015) was conducted. Included were randomized controlled trials that compared 6 months (or less) of DAPT (defined as acetylsalicylic acid 75-200mg daily and a P2Y12 inhibitor) to the standard of 12 months. Outcomes of interest included death (all-cause and cardiac), myocardial infarction (MI), definite/probable stent thrombosis, and bleeding (major and overall). An odds ratio (OR) and 95% confidence interval (CI) were calculated for each outcome using a random effects model. RESULTS Six trials (five open-label, one double-blind) were included (N=13,900). Four studies investigated 6 months of DAPT, and two studies investigated 3 months. Median follow-up was 12 months. There was no statistically significantly difference between groups regarding all-cause death (OR 0.88, 95% CI 0.64-1.20), cardiac death (OR 1.00, 95% CI 0.64-1.55), MI (OR 1.16, 95% CI 0.87-1.56), and stent thrombosis (OR 1.22, 95% CI 0.70-2.15). Both major and any bleeding were significantly decreased with shorter-term DAPT (OR 0.58, 95% CI 0.34-0.98, and OR 0.62, 95% CI 0.47-0.81, respectively). CONCLUSIONS Shorter duration (3-6 months) of DAPT, as compared to 12 months, was not associated with a higher risk of death, MI, or stent thrombosis, but a lower rate of major and overall bleeding.

Coenzyme Q10 supplementation in the management of statin-associated myalgia

Statins are indicated for use as first-line therapy in the prevention of major adverse cardiovascular events (e.g., myocardial infarction, stroke) in patients with or at risk for cardiovascular disease.[1][1] However, muscle-related adverse effects, including myopathy, often limit the use of statins

Applying the guidelines for pharmacists integrating into primary care teams.

Background: In 2013, Jorgenson et al. published guidelines for pharmacists integrating into primary care teams. These guidelines outlined 10 evidence-based recommendations designed to support pharmacists in successfully establishing practices in primary care environments. The aim of this review is to provide a detailed, practical approach to implementing these recommendations in real life, thereby aiding to validate their effectiveness. Methods: Both authors reviewed the guidelines independently and ranked the importance of each recommendation respective to their practice. Each author then provided feedback for each recommendation regarding the successes and challenges they encountered through implementation. This feedback was then consolidated into agreed upon statements for each recommendation. Results and Discussion: Focusing on building relationships (with an emphasis on face time) and demonstrating value to both primary care providers and patients were identified as key aspects in developing these new roles. Ensuring that the environment supports the practice, along with strategic positioning within the clinic, improves uptake and can maximize the usefulness of a pharmacist in primary care. Demonstrating consistent and competent clinical and documentation skills builds on the foundation of the other recommendations to allow for the effective provision of clinical pharmacy services. Additional recommendations include developing efficient ways (potentially provider specific) to communicate with primary care providers and addressing potential preconceived notions about the role of the pharmacist in primary care. Conclusion: We believe these guidelines hold up to real-life integration and emphatically recommend their use for new and existing primary care pharmacists.

Adverse drug reactions: The importance of maintaining pharmacovigilance

In 2004, the anti-inflammatory drug rofecoxib was voluntarily withdrawn from the market due to cardiovascular safety concerns. Although this case was highly publicized, it was not an isolated example. Between 1997 and 2011, 25 drugs were withdrawn from the Canadian market due to safety concerns identified through postmarketing surveillance or pharmacovigilance. Identification and reporting of suspected adverse drug reactions through pharmacovigilance is an important patient safety activity that is the responsibility of all clinicians, especially pharmacists. It is particularly important for newer drugs, as rare adverse effects are not always identified in clinical trials and the prescribing of medications in the “real world” often yields new drug-related safety concerns. In this article, we aim to explore the ongoing monitoring and assessment of suspected drug-related adverse effects and discuss recent examples of newly identified drug safety concerns.

Effect of Glucagon-like Peptide-1 Receptor Agonists on All-cause Mortality and Cardiovascular Outcomes: A Meta-analysis

BACKGROUND Cardiovascular disease is the leading cause of death in patients with type 2 diabetes. OBJECTIVE To assess the impact of glucagon-like peptide-1 receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant outcomes including all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart failure, in patients with type 2 diabetes. METHODS EMBASE, MEDLINE, and CENTRAL were searched (inception to September 2016) for randomized, double-blind, placebo-controlled trials of at least one year in duration that compared any GLP1RA to placebo in patients with type 2 diabetes. Both authors independently completed the literature search, data extraction, and risk of bias assessment. For each outcome, a Risk Ratio (RR) and 95% Confidence Interval (CI) were calculated using a Mantel-Haenszel random effects model. RESULTS Eight trials (three albiglutide, two lixisenatide, two liraglutide, one semaglutide) consisting of 21,135 patients were included. Most patients had, or were at high risk for, cardiovascular disease. Follow- up ranged from 1-3.8 years. Trials contributing the majority of data were deemed to have a low risk of bias. The risk of all-cause mortality was lowered by 11% in patients receiving a GLP1RA (RR 0.89, 95% CI 0.81-0.99). There was no statistically significant difference between groups with respect to cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalizations for heart failure. CONCLUSION GLP1RA therapy when compared to placebo reduced all-cause mortality in high cardiovascular risk patients with type 2 diabetes. They did not impact cardiovascular mortality, nonfatal MI, nonfatal stroke, or heart failure hospitalizations.

Prevention and management of statin adverse effects: A practical approach for pharmacists:

Statin-associated adverse effects, primarily muscle-related symptoms, occur in up to approximately one-third of patients in clinical practice. Recently, a Canadian Consensus Working Group outlined 6 key principles to assess and manage patients with goal-inhibiting statin intolerance, defined as a syndrome characterized by symptoms or biomarker abnormalities that prevent the long-term use of and adherence to indicated statin therapy, which includes a trial of at least 2 statins and precludes reversible causes of statin adverse effects. These principles ensure patients are appropriately receiving a statin and aware of both the benefits and risks of therapy. As well, they address factors that may increase the risk of statin-associated myopathy. A thorough assessment of patients’ clinical and laboratory history should be performed in any patient presenting with muscle symptoms on statin therapy, followed by a systematic dechallenge/rechallenge approach. In practice, most patients with statin intolerance due to muscle symptoms will be able to tolerate another statin. This is of particular importance because of the relative paucity of compelling evidence demonstrating a cardiovascular benefit with nonstatin therapies. Pharmacists are ideally situated to provide patient education, recommend changes to therapy and monitor patients with goal-inhibiting statin intolerance.