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Competing Interests: The authors declare no potential or actual conflict of interest with respect to research, authorship and/or publication of this article.

Competing Interests: Declaration of Conflicting Interests: The authors have no financial or other conflicts of interest related to this work.

Competing Interests: Statement of Conflicting Interests:The authors all declare that they have no financial or other conflicts of interest related to this work.

Objective: To evaluate the effects of switching from ticagrelor or prasugrel to clopidogrel in acute coronary syndrome (ACS) patients managed with percutaneous coronary intervention on major adverse cardiovascular events (MACEs) and bleeding. Data Sources: We searched MEDLINE, EMBASE, CENTRAL, bibliographies of relevant articles, and clinicaltrials.gov for eligible articles published from inception to January 27, 2019. Study Selection and Data Extraction: We included randomized controlled trials (RCTs) and cohort and case-control studies that reported on ≥1 outcome of interest. Primary outcomes were MACE and major bleeding, and the secondary outcome was any bleeding. Data Synthesis: From 483 articles, we included 7 relevant studies (2 RCTs, 5 cohort studies) at high/unclear risk of bias. Random-effects meta-analysis revealed inconclusive effects on MACE (hazard ratio [HR] = 1.00, 95% CI = 0.59-1.68; I 2 = 82%), major bleeding (HR = 0.51; 0.19-1.35; I 2 = 91%), and any bleeding (HR = 0.64; 0.38-1.07; I 2 = 85%). Similar nonsignificant results were obtained in secondary analyses evaluating risk ratios. Relevance to Patient Care and Clinical Practice: Ticagrelor and prasugrel, are now considered preferred therapy over clopidogrel in patients with ACS. Switching from these potent P2Y 12 inhibitors to clopidogrel is commonly performed to reduce bleeding risk, other adverse effects, or costs. Current best-available evidence is inconclusive regarding the effects of switching to clopidogrel on the risk of MACE and bleeding. Overall, studies were underpowered to detect clinically important differences. Conclusions: Until adequately powered trials demonstrate an advantage to switching to clopidogrel from prasugrel or ticagrelor, clinicians may consider this approach as clinically indicated on an individual, case-by-case basis.

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., Competing Interests: Declaration of Conflicting Interests:The authors have no real or potential financial conflicts of interest related to this work. Drs. Barry and Pearson were members of the primary panel and coauthors of the 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Dr. Pearson is a member of the Canadian Consensus Working Group and coauthor of the 2016 update for the diagnosis, prevention and management of statin adverse effects and intolerance.

Competing Interests: Declaration of Conflicting Interest:The authors declare no potential or actual conflict of interest with respect to research, authorship and/or publication of this article.

Background: Dyslipidemia is an important risk factor for cardiovascular disease but is suboptimally managed. Pharmacists are accessible primary care professionals and with expanded scopes of practice (including prescribing), could identify and manage patients with dyslipidemia. We sought to evaluate the effect of pharmacist prescribing of dyslipidemia medications on the proportion of participants achieving target LDL-cholesterol (LDL-c) levels., Methods: We conducted a randomized controlled trial in 14 community pharmacies in Alberta, Canada. We enrolled adults with uncontrolled dyslipidemia as defined by the 2009 Canadian Dyslipidemia Guidelines. Intervention was pharmacist-directed dyslipidemia care, including assessment of cardiovascular risk, review of LDL-c, prescribing of medications, health behaviour interventions and follow-up every 6 weeks for 6 months. Usual care patients received their lipid results and a pamphlet on cardiovascular disease and usual care from their physician and pharmacist. Primary outcome was the proportion of participants achieving their target LDL-c (<2 mmol/L or ≥50% reduction) at 6 months between groups., Results: We enrolled 99 patients with a mean (SD) age of 63 (13) years, 49% male and baseline LDL-c of 3.37 mmol/L (0.98). Proportion of patients achieving LDL-c target was 43% intervention versus 18% control ( p = 0.007). Adjusted odds of achieving target LDL-c were 3.3 times higher for the intervention group ( p = 0.031), who also achieved greater reduction in LDL-c (1.12 mmol/L, SE = 0.112) versus control (0.42 mmol/L, SE = 0.109), for an adjusted mean difference of 0.546 mmol/L (SE = 0.157), p < 0.001., Conclusion: Pharmacist prescribing resulted in >3-fold more patients achieving target LDL-c levels. This could have major public health implications., Competing Interests: Declaration of Conflicting Interests:The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Evolving scope of practice has led pharmacists to develop new skills traditionally performed by other members of the health care team, including physical examination (PE). A session to teach PE skills to pharmacists was created as part of a professional development program. The purpose of this study was to evaluate participants' perception of, barriers to and confidence in performing PE before and after the session., Methods: A 2-hour session introduced participants to PE as part of a primary care professional development program. Surveys were administered before and after the session, and then 4 weeks later. Participants' confidence in performing PE was assessed using a 4-point unipolar scale questionnaire, and mean weighted responses were compared between the pre- and post-session surveys., Results: Thirty-four pharmacists participated in the study. At baseline, 82.4% had never received formal PE education, but 38.2% performed PE in practice, including blood pressure measurement. Eighty-two percent of participants identified barriers to performing PE, the most common being lack of formal training. Participants' confidence with PE significantly increased between the pre- and post-session surveys, except for comfort with making drug therapy interventions based on PE findings. Forty-three percent of participants completed the 4-week follow-up survey, which demonstrated that the use of PE in practice remained unchanged., Conclusion: Prior to the session, most participants did not use PE in their practice, primarily due to a lack of formal training. The session significantly improved participants' confidence in PE, but this did not translate into short-term practice change.

Objective: To review the efficacy and safety of colchicine as primary and secondary prophylaxis for pericarditis., Data Sources: We searched MEDLINE, EMBASE, PubMed, BIOSIS Previews, International Pharmaceutical Abstracts, Web of Science, and CENTRAL for controlled studies from database inception date to July 2009. Search terms included colchicine, pericarditis, and postpericardiotomy syndrome (PPS)., Study Selection and Data Extraction: Prospective, randomized, controlled trials investigating the use of colchicine in preventing pericarditis were included. Data extracted included design, inclusion criteria, demographics, interventions, background therapy, and pericarditis-related clinical outcomes., Data Synthesis: Data were synthesized qualitatively, given variable study designs. Three trials were identified. A single trial examining primary prevention evaluated the use of colchicine versus placebo for preventing PPS in patients undergoing cardiopulmonary bypass grafting. No significant reduction in PPS was found. Two studies examined secondary prevention of pericarditis, comparing colchicine plus aspirin versus aspirin alone. One study examined using these comparators to treat a first episode of pericarditis. After 3 months, there was a significant reduction in recurrent pericarditis with colchicine plus aspirin (11.7% vs 33%; p = 0.009). Another study examined this same regimen in recurrent pericarditis, finding a significant reduction in recurrence after 6 months (21% vs 45%; p = 0.02)., Conclusions: Despite limitations in study designs, current evidence suggests a role for colchicine in the secondary prophylaxis for recurrent pericarditis. The evidence for use of colchicine as primary prophylaxis in PPS is indeterminate; therefore, colchicine cannot be recommended routinely. While colchicine should be recommended for the prevention of recurrent pericarditis, questions regarding the optimal regimen and long-term safety profile need to be further elucidated.

Objective: To report the case of an orthotopic heart transplant recipient who developed rhabdomyolysis precipitated by the addition of clopidogrel to the existing regimen of cyclosporine and atorvastatin, which had been tolerated for more than 3 years without adverse effects or laboratory evidence of myositis., Case Summary: Fourteen years after cardiac transplantation, a 58-year-old woman began a planned 4 week course of clopidogrel 75 mg/day following coronary angioplasty and placement of a stent in the left circumflex coronary artery. Almost 4 weeks later, she presented with severe muscle pain and weakness and laboratory evidence of rhabdomyolysis, with marked elevations of plasma creatine kinase (96,000 U/L) and urine myoglobin (332,872 microg/L) as well as early acute renal failure (serum creatinine 2.9 mg/dL). Symptoms and laboratory abnormalities resolved with cessation of cyclosporine, atorvastatin, and clopidogrel. Clopidogrel was not restarted, while atorvastatin and cyclosporine were; the patient had no recurrence of symptoms up to 15 months later., Discussion: Both atorvastatin and cyclosporine, as well as clopidogrel's active thiol derivative, are metabolized by the cytochrome P450 3A4 isoenzyme. Cyclosporine is also a moderate inhibitor of this isoenzyme. We postulate that competition between atorvastatin and clopidogrel for CYP3A4 receptors, already partially inhibited by cyclosporine, led to increased atorvastatin concentrations, resulting in the acute onset of rhabdomyolysis. This theory is further supported by the patient's continued ability to tolerate the combination of atorvastatin and cyclosporine, without clopidogrel, on rechallenge. Use of the Naranjo probability scale revealed that rhabdomyolysis was probably precipitated by the addition of clopidogrel to the stable baseline regimen of cyclosporine and atorvastatin., Conclusions: Practitioners must be conscious of the potential for adverse effects when prescribing clopidogrel to heart transplant patients who are concomitantly receiving cyclosporine and a statin. If concomitant administration is required, careful clinical and laboratory monitoring of the patient is necessary.

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 < or = 97 mg/dL, as recommended by national guidelines. After 2 months of ezetimibe, the patient's 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 (> or = 5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.

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.