Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions.

Background: One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual. Systematic Review Registration: PROSPERO no. 135886.

Why a distinct medical stream is necessary to support patients using cannabis for medical purposes.

BACKGROUND: Since 2001, Canadians have been able to obtain cannabis for medical purposes, initially through the Access to Cannabis for Medical Purposes Regulations (ACMPR). The Cannabis Act (Bill C-45) came into force on October 17, 2018, replacing the ACMPR. The Cannabis Act enables Canadians to possess cannabis purchased from a licensed retailer without authorization for either medical or nonmedical purposes. The Cannabis Act is currently the guiding legislation which governs both medical and nonmedical access. The Cannabis Act contains some improvements for patients but is essentially the same as its previous legislation. Beginning in October 2022, the federal government is conducting a review of the Cannabis Act and is questioning whether a distinct medical cannabis stream is still required, given the ease of access to cannabis and cannabis products. Although there is overlap in the reasons for medical and recreational cannabis use, the distinct legislation of medical versus recreational use of cannabis in Canada may be under threat. MAIN BODY: A large segment of the medical, academic, research, and lay communities agree that there is a need for distinct medical and recreational cannabis streams. Perhaps most importantly, separation of these streams is necessary to ensure that both medical cannabis patients and healthcare providers receive the required support needed to optimize benefits while minimizing risks associated with medical cannabis use. Preservation of distinct medical and recreational streams can help to ensure that needs of different stakeholders are met. For example, patients require guidance in the form of assessing the appropriateness of cannabis use, selection of appropriate products and dosage forms, dosing titration, screening for drug interactions, and safety monitoring. Healthcare providers require access to undergraduate and continuing health education as well as support from their professional organizations to ensure medical cannabis is appropriately prescribed. Although there are challenges in conducing research, as motives for cannabis use frequently straddle boundaries between medical versus recreational cannabis use, maintenance of a distinct medical stream is also necessary to ensure adequate supply of cannabis products appropriate for medical use, to reduce stigma associated with cannabis in both patients and providers, to help enable reimbursement for patients, to facilitate removal of taxation on cannabis used for medical purposes, and to promote research on all aspects of medical cannabis. CONCLUSION: Cannabis products for medical and recreational purposes have different objectives and needs, requiring different methods of distribution, access, and monitoring. HCPs, patients, and the commercial cannabis industry would serve Canadians well to continue to advocate to policy makers to ensure the continued existence of two distinct streams and must strive to make ongoing improvements to the current programs.

Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions

One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual.

Colchicine for Prevention of Atherothrombotic Events in Patients With Coronary Artery Disease: Review and Practical Approach for Clinicians.

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1ß/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions-within 30 days and, ideally, within 3 days-or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.

Fragility fracture identifies patients at imminent risk for subsequent fracture: real-world retrospective database study in Ontario, Canada.

BACKGROUND: The secondary fracture prevention gap in the osteoporosis field has been previously described as a 'crisis'. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1-2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures. METHODS: This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized. RESULTS: Among 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236-955). For each index fracture site examined, median time from index to second fracture was < 2 years. The proportion of patients with BMD assessment was 10.3% ≤1 year prior to and 16.4% ≤1 year post index fracture. The proportion of patients receiving osteoporosis therapy was 29.8% ≤1 year prior, 34.6% ≤1 year post, and 25.9% > 3 years post index fracture. CONCLUSIONS: This cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

Non-vitamin K antagonist oral anticoagulant (NOAC) use and dosing in Canadian practice: Insights from the optimising pharmacotherapy in the management approach to lowering risk in atrial fibrillation (OPTIMAL AF) Programme.

AIMS: To estimate the rate of non-vitamin K oral anticoagulant (NOAC) dosing that is lower- and higher-than-recommended and to describe the reasons for NOAC dose discordance with Health Canada prescribing information. METHODS: The OPTIMAL AF Programme was an observational cohort quality assessment initiative in which primary and specialty care physicians in eight provinces provided a snapshot of their anticoagulated non-valvular atrial fibrillation (NVAF) patients through either an electronic medical record (EMR) system or standardised, paper-based data collection methods. RESULTS: Data on 1681 NVAF patients receiving oral anticoagulation (OAC) for stroke prevention was provided by 102 physicians. A NOAC was prescribed in 1379 patients (8%). The standard recommended dose was prescribed in 849 (76%) and reduced dose in 264 (24%). Concordance of the reduced dose with Health Canada prescribing information occurred in 154 patients (58%). The standard dose was concordant in 805 (95%). The main reasons for the use of discordant reduced doses were age of 80 years or more, elevated creatinine, prior bleeding or dose recommended by specialist. DISCUSSION AND CONCLUSION: The vast majority of Canadian patients meeting the Canadian Cardiovascular Society (CCS) guideline recommendations for OAC to decrease AF-related stroke risk were receiving product monograph-concordant NOAC dosing (85%). Nonetheless, this highlights the fact that an important proportion of patients were prescribed doses that are discordant and opportunities remain to improve NOAC dosing to optimise stroke prevention.

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation.

BACKGROUND: Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain. METHODS: We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male). RESULTS: Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians. CONCLUSIONS: Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation.

2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents.

Use of Evidence-Based Therapy for Cardiovascular Risk Factors in Canadian Outpatients With Atrial Fibrillation: From the Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation (FREEDOM AF) and Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation (CONNECT AF).

Using data collected from 2 national atrial fibrillation (AF) primary care physician chart audits (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation [FREEDOM AF] and Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation [CONNECT AF]), we evaluated the frequency of, and factors associated with, the use of cardiovascular (CV) evidence-based therapies in Canadian AF outpatients with at least 1 CV risk factor or co-morbidity. Of the 11,264 patients enrolled, 9,495 (84.3%) were eligible for one or more CV evidence-based therapies. The proportions of patients with AF receiving all eligible guideline-recommended therapies were 40.8% of patients with coronary artery disease, 48.9% of patients with diabetes mellitus, 40.2% of patients with heart failure, 96.7% of patients with hypertension, and 55.1% of patients with peripheral arterial disease. Factors that were independently associated with nonreceipt of all indicated evidence-based therapies included sinus rhythm rather than AF at baseline and liver disease. In conclusion, although most Canadian outpatients with AF have CV risk factors or co-morbidities, a substantial portion of these patients did not receive all guideline-recommended therapies. These findings suggest that there is an opportunity to improve the quality of care for patients with AF in Canada.

Appropriate Use of Antithrombotic Medication in Canadian Patients With Nonvalvular Atrial Fibrillation.

This national chart audit of 7,019 patients with nonvalvular atrial fibrillation (AF) from 735 primary care physician practices sought to examine the management of Canadian patients with AF through an evidence-based, guideline-recommended approach. The appropriate use of oral anticoagulants (OACs) in this patient population and the potential factors guiding OAC choice were examined. Suboptimal dosing was seen. In patients on warfarin, 30.9% had not achieved a time in therapeutic range (TTR) in excess of 65% and, despite current Canadian guideline recommendations, were continued on warfarin rather than one of the novel OACs. In patients who received no antithrombotic therapy, 65.5% met criteria for treatment with an OAC. In addition, 62.8% of patients who were treated with acetylsalicylic acid monotherapy met guideline criteria for the use of an OAC. In those patients treated with an OAC, 24.8% were not on the recommended dose based on the product monograph or, if on warfarin, had a TTR <65%. Of the patients on novel OACs (NOACs), 7.4% of patients were underdosed, whereas overdosing was seen in 4.3%. Factors that may have contributed to dosing outside recommendations included underestimation of stroke risk, overestimation of bleed risk, compliance concerns, and lack of provincial reimbursement. In conclusion, significant correctable gaps remain in optimal treatment for stroke prevention in AF.

Risk stratification and stroke prevention therapy care gaps in Canadian atrial fibrillation patients (from the Co-ordinated National Network to Engage Physicians in the Care and Treatment of Patients With Atrial Fibrillation chart audit).

The objectives of this national chart audit (January to June 2013) of 6,346 patients with atrial fibrillation (AF; ≥18 years without a significant heart valve disorder) from 647 primary care physicians were to (1) describe the frequency of stroke and bleed risk assessments in patients with nonvalvular AF by primary care physicians, including the accuracy of these assessments relative to established predictive indexes; (2) outline contemporary methods of anticoagulation used; and (3) report the time in the therapeutic range among patients prescribed warfarin. An annual stroke risk assessment was not undertaken in 15% and estimated without a formal risk tool in 33%; agreement with CHADS2 score estimation was seen in 87% of patients. Major bleeding risk assessment was not undertaken in 25% and estimated without a formal risk tool in 47%; agreement with HAS-BLED score estimation was observed in 64% with physician overestimation in 26% of patients. Antithrombotic therapy included warfarin (58%), dabigatran (22%), rivaroxaban (14%), and apixaban (<1%). Among warfarin-treated patients, the median international normalized ratio was 2.4 and time in therapeutic range (TTR) was 73%; however, the TTR was <50% in 845 (25%), 50% to 69% in 674 (20%), and ≥70% in 1,827 (55%) patients. In conclusion, we describe a contemporary real-world elderly population with AF at important risk for stroke. There is apparent overestimation of bleeding risk in many patients. Warfarin was the dominant stroke prevention treatment; however, the suggested TTR target was achieved in only 55% of these patients.

Focused 2012 update of the Canadian Cardiovascular Society guidelines for the use of antiplatelet therapy.

The initial 2010 Canadian Cardiovascular Society (CCS) Guidelines for the Use of Antiplatelet Therapy in the Outpatient Setting were published in May 2011. As part of a planned re-evaluation within 2 years, we conducted an extensive literature search encompassing all topics included in the 2010 CCS Guidelines, and concluded that there were sufficient new data to merit revisiting the guidance on antiplatelet therapy for secondary prevention in the first year after acute coronary syndrome (ACS), percutaneous coronary intervention, or coronary artery bypass grafting, and the interaction between clopidogrel and proton pump inhibitors. In addition, new clinical trials information about the efficacy and safety of combining novel oral anticoagulants with antiplatelet therapy in ACS justified the addition of a new section of recommendations to the Guidelines. In this focused update, we provide recommendations for the use of clopidogrel, ticagrelor, and prasugrel in non-ST elevation ACS, avoidance of prasugrel in patients with previous stroke/transient ischemic attack, higher doses of clopidogrel (j) /day) for the first 6 days after ACS, and the preferential use of prasugrel or ticagrelor after percutaneous coronary intervention in ACS. For non-ACS stented patients, we recommend acetylsalicylic acid/clopidogrel for 1 year, with at least 1 month of therapy for bare-metal stent patients and 3 months for drug-eluting stent patients unable to tolerate year-long double therapy. We also consider therapy for patients with a history of stent thrombosis, the indications for longer-term treatment, discontinuation timing preoperatively, indications for changing agents, the management of antiplatelet therapy before and after bypass surgery, and use/selection of proton pump inhibitors along with antiplatelet agents.

The use of antiplatelet therapy in the outpatient setting: Canadian Cardiovascular Society guidelines.

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This full document has been summarized in an Executive Summary published in the Canadian Journal of Cardiology and may be found at http://www.ccs.ca/. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital following acute coronary syndromes, post-percutaneous coronary intervention, post-coronary artery bypass grafting, patients with a history of transient cerebral ischemic events or strokes, and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy/lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel and proton-pump inhibitors, or acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications.

The use of antiplatelet therapy in the outpatient setting: Canadian Cardiovascular Society Guidelines Executive Summary.

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This Executive Summary provides an abbreviated version of the principal recommendations. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital after acute coronary syndromes, percutaneous coronary intervention, or coronary artery bypass grafting; patients with a history of transient cerebral ischemic events or strokes; and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy or lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel, and proton-pump inhibitors, or aspirin and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications. The complete guidelines document is published as a supplementary issue of the Canadian Journal of Cardiology and is available at http://www.ccs.ca/.

Cardiovascular risk profiles and outcomes of Chinese living inside and outside China.

AIM: To assess whether cardiovascular risk differs among the Chinese living inside and outside mainland China. METHODS AND RESULTS: Three thousand, four hundred and eighty-two East Asians were enrolled in the REduction of Atherothrombosis for Continued Health Registry in mainland China, Hong Kong/Singapore/Taiwan, Western Europe, and North America. Baseline demographics, medication use, risk factor control, and 30-month cardiovascular outcomes of the 2938 patients with atherothrombotic disease were compared. Rates of hypertension, hypercholesterolemia, diabetes, abdominal obesity, and body mass index ≥25 kg/m² were lowest in mainland China, were increased in Hong Kong/Singapore/Taiwan, and were highest in Western Europe and North America. Diabetes prevalence was 23% in mainland China, approximately two-fold lower than the other regions. Antihypertensive, antidiabetic, and antiplatelet agent use was similar in all regions. Risk factor control was significantly poorer in Western Europe and, except for glucose control, significantly better in North America. Thirty-month nonfatal stroke rates were highest in mainland China and fell in a stepwise manner in more westernized societies. Conversely, nonfatal myocardial infarction rates increased in more westernized societies. CONCLUSION: Obesity and other risk factors progressively worsen as patients move from mainland China to Hong Kong/Singapore/Taiwan and overseas. Despite similar medication use, risk factor control and cardiovascular outcomes were significantly different. The magnitude of these changes is larger than formerly estimated, suggesting population differences in cardiovascular risk and disease prevalence, likely to be more closely associated with lifestyle and cultural habits than genetic differences.