Adherence to direct or vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a long-term observational study.

Our objectives were to measure long-term adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and to identify patient factors associated with adherence. Using linked, population-based administrative data from British Columbia, Canada, an incident cohort of adults prescribed OACs for AF was identified. We calculated the proportion of days covered (PDC) as a time-dependent covariate for each 90-day window from OAC initiation until the end of follow-up. Associations between patient attributes and adherence were assessed using generalized mixed effect linear regression models. 30,264 patients were included. Mean PDC was 0.69 (SD 0.28) over a median follow-up of 6.7 years. 54% of patients were non-adherent (PDC < 0.8). After controlling for confounders, factors positively associated with adherence were number of drug class switches, history of stroke or transient ischemic attack, history of vascular disease, time since initiation, and age. Age > 75 years at initiation, polypharmacy (among VKA users only), and receiving DOAC (vs. VKA) were negatively associated with adherence. PDC decreased over time for VKA users and increased for DOAC users. Over half of AF patients studied were, on average, nonadherent to OAC therapy and missed 32% of their doses. Several patient factors were associated with higher or lower adherence, and adherence to VKA declined during therapy while DOAC adherence increased slightly over time. To min im ize the risk stroke, adherence-supporting interventions are needed for all patients with AF, particularly those aged > 75 years, those with prior stroke or vascular disease, VKA users with polypharmacy, and DOAC recipients.

The Random Effects Warfarin Days' Supply (REWarDS) Model: Development and Validation of a Novel Method for Estimating Exposure to Warfarin Using Administrative Data.

Warfarin's complex dosing is a significant barrier to measurement of its exposure in observational studies using population databases. Using population-based administrative data (1996-2019) from British Columbia, Canada, we developed a method based on statistical modeling (Random Effects Warfarin Days' Supply (REWarDS)) that involves fitting a random-effects linear regression model to patients' cumulative dosage over time for estimation of warfarin exposure. Model parameters included a minimal universally available set of variables from prescription records for estimation of patients' individualized average daily doses of warfarin. REWarDS estimates were validated against a reference standard (manual calculation of the daily dose using the free-text administration instructions entered by the dispensing pharmacist) and compared with alternative methods (fixed window, fixed tablet, defined daily dose, and reverse wait time distribution) using Pearson's correlation coefficient (r), the intraclass correlation coefficient, and the root mean squared error. REWarDS-estimated days' supply showed strong correlation and agreement with the reference standard (r = 0.90 (95% confidence interval (CI): 0.90, 0.90); intraclass correlation coefficient = 0.95 (95% CI: 0.94, 0.95); root mean squared error = 8.24 days) and performed better than all of the alternative methods. REWarDS-estimated days' supply was valid and more accurate than estimates from all other available methods. REWarDS is expected to confer optimal precision in studies measuring warfarin exposure using administrative data.

Therapeutic Controversies in the Medical Management of Valvular Heart Disease.

OBJECTIVE: To evaluate the evidence for common therapeutic controversies in the medical management of valvular heart disease (VHD). DATA SOURCES: A literature search of PubMed (inception to December 2020) was performed using the terms angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and aortic stenosis (AS); and adrenergic ß-antagonists and aortic valve regurgitation (AR) or mitral stenosis (MS). STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) and meta-analyses conducted in humans and published in English that reported ≥1 clinical outcome were included. DATA SYNTHESIS: Nine articles were included: 3 RCTs and 1 meta-analysis for ACE inhibitors/ARBs in AS, 1 RCT for ß-blockers in AR, and 4 RCTs for ß-blockers in MS. Evidence suggests that ACE inhibitors/ARBs do not increase the risk of adverse outcomes in patients with AS but may delay valve replacement. ß-Blockers do not appear to worsen outcomes in patients with chronic AR and may improve left-ventricular function in patients with a reduced ejection fraction. ß-Blockers do not improve and may actually worsen exercise tolerance in patients with MS in sinus rhythm. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: ACE inhibitors/ARBs and ß-blockers can likely be safely used in patients with AS or AR, respectively, who have a compelling indication. There is insufficient evidence to recommend routine use of ß-blockers in patients with MS without atrial fibrillation. CONCLUSIONS: Common beliefs about the medical treatment of VHD are not supported by high-quality data. There remains a need for larger-scale RCTs in the medical management of VHD.

Treatment of chronic noncancer pain in patients on opioid therapy in primary care: A retrospective cohort study.

BACKGROUND: This study sought to characterize the real-world treatment of chronic noncancer pain (CNCP) in patients on opioid therapy in primary care. METHODS: A retrospective cohort study from 2014-18 was conducted at a multidisciplinary primary care clinic in Chilliwack, British Columbia. Included were adults on daily opioid therapy for CNCP. Patients receiving palliative care or ≤1 visit were excluded. Outcomes of interest included use of opioid/nonopioid pharmacotherapy, number/frequency of visits and proportion of patients able to reduce/discontinue opioid therapy. RESULTS: Seventy patients (mean age 53 years, 53% male, 51% back pain) were included. Median follow-up was 6 visits over 12 months. Sixty-two patients (89%) reduced their opioid dose, 6 patients had no change and 2 patients required a dose increase. Mean opioid dose was reduced from 183 to 70 mg morphine equivalents daily. Twenty-four patients (34%) discontinued opioid therapy, 6 patients (9%) transitioned to opioid agonist therapy and 6 patients (9%) breached their opioid treatment agreement. Nonopioid pharmacotherapy included nonsteroidal anti-inflammatory drugs (64%), gabapentinoids (63%), tricyclic antidepressants (56%) and nabilone (51%). DISCUSSION: Over half of patients were no longer on opioid therapy by the end of the study. Most patients had a disorder (e.g., back pain) for which opioids are generally not recommended. Overall mean opioid dose was reduced from baseline by approximately 60% over 1 year. Lack of access to specialized pain treatments may have accounted for high nonopioid pharmacotherapy usage. CONCLUSIONS: This study demonstrates that treatment of CNCP and opioid tapering can successfully be achieved in a primary care setting. Can Pharm J (Ott) 2020;153:xx-xx.

Use of low-dose acetylsalicylic acid for cardiovascular disease prevention: A practical, stepwise approach for pharmacists.

Low-dose acetylsalicylic acid (ASA) is recommended in patients with established cardiovascular disease. However, the role of ASA in those without cardiovascular disease (i.e., primary prevention) is less clear, which has led to discordance among Canadian guidelines. In 2018, 3 double-blind, randomized controlled trials were published that evaluated ASA 100 mg daily versus placebo in patients without established cardiovascular disease. In the ASPREE trial, ASA did not reduce the risk of all-cause death, dementia, or persistent physical disability in patients ≥70 years of age but increased the risk of major bleeding. In the ARRIVE trial, ASA failed to lower the risk of a composite of cardiovascular events but increased any gastrointestinal bleeding in patients at intermediate risk of cardiovascular disease. In the ASCEND trial, ASA significantly reduced the primary composite cardiovascular outcome in patients with diabetes for a number needed to treat of 91 over approximately 7.4 years. Yet major bleeding was increased with ASA for a number needed to harm of 112. Therefore, in most situations, ASA should not be recommended for primary cardiovascular prevention. However, there are additional indications for ASA beyond cardiovascular disease. Thus, a sequential algorithm was developed based on contemporary evidence to help pharmacists determine the suitability of ASA in their patients and play an active role in educating their patients about the potential benefits (or lack thereof) and risks of ASA. Can Pharm J (Ott) 2020;153:xx-xx.

Patients' perceptions and use of natural health products.

BACKGROUND: Despite a lack of good scientific evidence for their benefit, Canadians take a lot of natural health products (NHPs). The objectives of this study were to determine patients' perception of the efficacy, safety and quality of NHPs and to characterize NHP use. METHODS: A standardized, 18-question survey was distributed to the general public through a variety of methods. RESULTS: A total of 326 individuals completed the survey. Eighty-five percent of respondents take 1 or more NHPs. Forty-seven percent agreed/strongly agreed that NHPs are safer than prescription medications and 24% disagreed/strongly disagreed that prescription medications are more effective than NHPs. Three-quarters of respondents agreed/strongly agreed that health care providers should recommend NHPs more often, as most stated they preferred to take an NHP for both a minor ailment (82%) and chronic medical condition (60%). Respondents used 124 different NHPs, most commonly vitamin D, vitamin B and magnesium. Respondents purchased NHPs primarily from health/vitamin stores (66%) and accessed the Internet for information about them (64%). Younger, female respondents were more likely to take NHPs. DISCUSSION: Patients appear to be comfortable foregoing education from health care professionals about the benefits and risks of NHPs. Patients' comfort with self-prescribing NHPs seems to stem from a perception of general efficacy and quality with little to no concern about harm and appears to be strongly influenced by lay sources of information. CONCLUSION: Most respondents take 1 or more NHPs, preferring to use NHPs over prescription medications for minor and chronic health concerns seemingly based on a perception of safety and quality.

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.

Development of a Pharmacist REferral Program in a primary cARE clinic (PREPARE): A prospective cross-sectional study.

BACKGROUND: Increasing demand for ambulatory health care services has led to the development of primary care multidisciplinary teams that include pharmacists. The objective of this study was to characterize referrals to a pharmacist in a primary care clinic (PCC) based in Chilliwack, British Columbia. METHODS: This prospective cross-sectional study included all patients referred to the PCC pharmacist over 12 months (May 2015 to April 2016). Data regarding the source/reason for referral, patient demographics, medical problems/medications and number/category of identified drug therapy concerns (DTCs) were collected. RESULTS: A total of 137 referrals were received. Mean age was 60 years and 59% were female. Twenty patients (15%) did not attend their appointment. Fifty-eight percent were new clinic patients identified using a Medication Risk Assessment Questionnaire (MRAQ), 30% were from PCC clinicians and 12% were from community family physicians. The most common reason for referral was for a medication review (82%). Median number of medical problems and medications per patient were 7 (interquartile range [IQR] 5) and 11 (IQR 7.5), respectively. A total of 460 DTCs were identified (median 4 per patient, IQR 3.5), of which 34% were medication without an indication and 28% an untreated indication. DISCUSSION AND CONCLUSION: The most common source of referrals to a PCC pharmacist was for medication reviews of new patients using an MRAQ. Most referred patients had multiple medical problems and polypharmacy, and few were referred for disease-specific management. The number of DTCs per patient was variable and, despite polypharmacy being commonplace, almost one-third of patients had an untreated indication.

Familial hypercholesterolemia: Review of diagnosis, screening, and treatment.

OBJECTIVE: To summarize the pathophysiology, epidemiology, screening, diagnosis, and treatment of familial hypercholesterolemia (FH). QUALITY OF EVIDENCE: A PubMed search was conducted (inception to July 2014) for articles on pathophysiology, screening, diagnosis, and management of FH, supplemented with hand searches of bibliographies of guidelines and reviews. A supporting level of evidence for each recommendation was categorized as level I (randomized controlled trial or systematic review of randomized controlled trials), level II (observational study), or level III (expert opinion). The best available evidence is mostly level II or III. MAIN MESSAGE: Familial hypercholesterolemia affects 1 in 500 Canadians. Risk of a coronary event is high in these patients and is underestimated by risk calculators (eg, Framingham). Clinicians should screen patients according to guidelines and suspect FH in any patient with a premature cardiovascular event, physical stigmata of hypercholesterolemia, or an elevated plasma lipid level. Physicians should diagnose FH using either the Simon Broome or Dutch Lipid Network criteria. Management of heterozygous FH includes reducing low-density lipoprotein levels by 50% or more from baseline with high-dose statins and other lipid-lowering agents. Clinicians should refer any patient with homozygous FH to a specialized centre. CONCLUSION: Familial hypercholesterolemia represents an important cause of premature cardiovascular disease in Canadians. Early identification and aggressive treatment of individuals with FH reduces cardiovascular morbidity and mortality.

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.

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.