Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) guideline for the prevention and management of cardiovascular disease in primary care: 2018 update
==============================================================================================================================================================================

* Sheldon W. Tobe
* James A. Stone
* Todd Anderson
* Simon Bacon
* Alice Y.Y. Cheng
* Stella S. Daskalopoulou
* Justin A. Ezekowitz
* Jean C. Gregoire
* Gord Gubitz
* Rahul Jain
* Karim Keshavjee
* Patty Lindsay
* Mary L’Abbe
* David C.W. Lau
* Lawrence A. Leiter
* Eileen O’Meara
* Glen J. Pearson
* Doreen M. Rabi
* Diana Sherifali
* Peter Selby
* Jack V. Tu
* Sean Wharton
* Kimberly M. Walker
* Diane Hua-Stewart
* Peter P. Liu

KEY POINTS
*   C-CHANGE promotes patient care by bringing nine guideline groups together, to provide a composite set of recommendations to help clinicians formulate a comprehensive treatment plan directed toward patient priorities.

*   The 2018 update to the C-CHANGE guideline includes a total of 77 recommendations and 52 recommendations that are newly added or updated.

*   A new category for hypertension for high-risk individuals has been developed with a new lower threshold for treatment (130 mm Hg systolic) and target blood pressure (< 120 mm Hg systolic).

*   Multifaceted care for patients with cardiovascular risks includes the cornerstones of health behaviour change, such as healthy eating and regular physical activity.

The Canadian Cardiovascular Harmonized National Guideline Endeavour (C-CHANGE) is a nationally endorsed guideline process, targeting primary care health care practitioners. The C-CHANGE guideline is a composite of nine of Canada’s cardiovascular-focused clinical practice guidelines (Table 1), chosen to meet primary care needs, including managing patients with multiple comorbidities, and since 2011 has been part of Canada’s robust and successful cardiovascular guideline efforts.8,9 Ninety percent of Canadians still have suboptimal cardiovascular health from multiple cardiovascular risk factors, higher rates of obesity and diabetes,15 and suboptimal control of hypertension, dyslipidemia and blood glucose.16 The compilation of the best available evidence into a nationally recognized and valuable set of best practices provides a common starting point for local and regional implementation strategies to achieve target control rates, including the enabling of interprofessional care. Putting evidence-based best practices into the hands of primary care health care practitioners may accelerate improved outcomes in Canada, but the main challenge is how best to implement the new recommendations, with efforts cognizant of local context and tailored to the needs of regional and local populations. The goal of the C-CHANGE process is for all Canadian health care practitioners to have easy access to a comprehensive and usable set of harmonized guidelines.

View this table:
[Table 1:](http://www.cmaj.ca/content/190/40/E1192/T1)

Table 1: 
C-CHANGE guideline partners and methodology

The third cycle of the C-CHANGE process was initiated as a result of many updates to the participating guidelines, including a complete update of the Canadian Association of Cardiovascular Prevention and Rehabilitation and Obesity Canada guidelines and the addition of guidelines on heart failure. In each C-CHANGE cycle, efforts are made to improve and harmonize guideline development with all partner organizations so that each guideline scores highly on the AGREE II (Appraisal of Guidelines for Research & Evaluation II) Instrument, which evaluates the process of guideline development and quality of reporting.17

The full 2018 C-CHANGE guideline update is available in Appendix 1, at [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1](http://www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1).

## Scope

This guideline is directed to primary health care providers caring for Canadian adults who have or are at risk of developing chronic cardiovascular diseases, including hypertension, diabetes, dyslipidemia, heart failure and stroke, and the risk factors for these conditions, including smoking, obesity and physical inactivity. The purpose of the C-CHANGE guideline is to bring together a comprehensive set of recommendations drawn from the nine participating guideline groups applicable to the care of people with multiple comorbidities. The aim is also to do this with sufficient rigour that health care practitioners and patients have confidence in the C-CHANGE process, as well as in the guidelines from the nine participating groups.

## Methods

### Guideline panel composition

This C-CHANGE guideline update was developed by a volunteer guideline panel, which is a scientific committee that reflects the authors of this paper and draws representation from each of the guideline partner organizations involved in the C-CHANGE process, along with primary care physicians with expertise in guideline dissemination (Appendix 2, available at [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1](http://www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1)). C-CHANGE works with each of the guideline groups to support quality improvement in guideline development in the domains outlined by the AGREE II Instrument.17 The C-CHANGE process uses a modified Delphi method to select a subset of all of the guideline partners’ recommendations that are appropriate for a primary care setting.8 Appendix 3, available at [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1](http://www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1), outlines the process and timeline undertaken for the 2018 C-CHANGE update.

### Guideline development

In the fall of 2016, the C-CHANGE guideline groups were contacted and agreed to participate in a consensus conference in June of 2017, as there were sufficient updates in the individual guideline groups to justify a C-CHANGE update and there was also the possibility that the heart failure guidelines would be ready for this C-CHANGE cycle (Appendix 3). Individual recommendations are chosen from each guideline group for inclusion in C-CHANGE to meet the needs of patients with the most common clusters of comorbidities, as hypertension, diabetes and dyslipidemia cluster together.18

The Canadian Cardiovascular Society’s heart failure group had been working with C-CHANGE for the last three years to update its guideline process and became the ninth major guidelines group to join the C-CHANGE collaboration. The addition of the heart failure recommendations had to wait until they were published in October 2017. From the 2017 comprehensive update of the Canadian Cardiovascular Society heart failure guideline, eight specific recommendations were chosen, using the modified Delphi process, as being the most appropriate for primary care health care practitioners, and were added to the C-CHANGE guideline.3 Agreements were established between the guideline groups about timing of publication of C-CHANGE and each individual group.

C-CHANGE ensures the quality of each partner guideline group using the AGREE II Instrument17 to assess the quality and reporting of the guideline. C-CHANGE performs an appraisal using AGREE II for the guideline groups; the appraisals can be found online ([www.cchangeguidelines.com](http://www.cchangeguidelines.com)). For more information on using AGREE II and the quality improvement process, see Appendix 4, available at [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1](http://www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.180194/-/DC1) (Quality Improvement in C-CHANGE Guideline).

### Management of competing interests

Funding for the C-CHANGE consensus conference and administrative support came from the Canadian Institutes of Health Research and in-kind support from the scientific and professional volunteers engaged in the process.

Seven of the nine guideline groups require their guideline panel members to disclose any potential competing interests by the time of their consensus conference, or early in the development process. Members with direct competing interests are asked to abstain from voting in the areas in which they have the conflict.

In the other two guideline groups, the Canadian Cardiovascular Society and the Canadian Action Network for the Advancement, Dissemination and Adoption of Practice-informed Tobacco Treatment, mitigation of competing interests and prevention of bias are approached by requiring a majority of their panel members in each guideline subgroup to have no relationships with industry; competing interests are declared early in the development process to ensure the required panel composition. In these two guideline subgroups, expert opinion from committee members with competing interests are welcomed at the consensus conference with the recognition of their potential bias. Experts in critical appraisal who have no competing interests make up the review committees to ensure the evidence has been assessed appropriately, and to provide a respected voice at the consensus discussions and debates, ensuring recommendations are aligned with the evidence. These experts in critical appraisal are part of the individual guideline groups and, for Diabetes Canada and Hypertension Canada, led the guideline development process (DS and DR, respectively). As leads of their respective processes, these two critical appraisal experts were also part of the C-CHANGE guideline process.

## Recommendations

The 2018 update to the C-CHANGE guideline includes a total of 77 recommendations originating from the nine partner guideline groups, including 52 recommendations that have been newly added or updated (Tables 2⇓⇓⇓⇓⇓–8). The ninth guideline (Canadian Cardiovascular Society Guidelines for the Management of Heart Failure)7 was added to C-CHANGE this year, with eight heart failure recommendations. The complete list of 2018 C-CHANGE recommendations is available in Appendix 1, with a full discussion of the evidence supporting each recommendation.

View this table:
[Table 2:](http://www.cmaj.ca/content/190/40/E1192/T2)

Table 2: 
Body habitus: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

View this table:
[Table 3:](http://www.cmaj.ca/content/190/40/E1192/T3)

Table 3: 
Diet, and sodium and alcohol intake: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

View this table:
[Table 4:](http://www.cmaj.ca/content/190/40/E1192/T4)

Table 4: 
Risk factor screening: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

View this table:
[Table 5:](http://www.cmaj.ca/content/190/40/E1192/T5)

Table 5: 
Diagnostic strategies: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

View this table:
[Table 6:](http://www.cmaj.ca/content/190/40/E1192/T6)

Table 6: 
Risk stratification: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

View this table:
[Table 7:](http://www.cmaj.ca/content/190/40/E1192/T7)

Table 7: 
Treatment targets: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

View this table:
[Table 8:](http://www.cmaj.ca/content/190/40/E1192/T8)

Table 8: 
Pharmacologic and procedural therapy for CVD risk reduction: New or updated recommendations in the 2018 C-CHANGE harmonized guideline*

In the recommendations, it was important to keep the focus on multifaceted optimal medical care, which remains a goal for people with diabetes and, by extension, those at higher risk of cardiovascular disease (Box 2). Management of multifaceted care in the ambulatory care setting is facilitated with an interprofessional team approach.

Box 1: 
### **Strength of recommendations and quality of evidence**

The individual guideline groups have a rigorous methodology to assess the quality of evidence for the development of guidelines, and these are listed in Table 1. There are two dimensions describing each of the recommendations: the first is the strength of the recommendation, and the second the quality of the evidence supporting it, based on quality and certainty. All Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) recommendations are “should do” or “should not do” recommendations and are considered to be strong. A “must do” recommendation is usually a policy to comply with health and safety recommendations, such as hand washing; a “could do” recommendation is one that some patients may opt out of because other options are less effective but more acceptable. The National Institute for Health and Clinical Excellence describes “should do” and “should not do” recommendations as interventions that, in most people, will lead to more good than harm.6

The second dimension describing the recommendation is the evidentiary base. C-CHANGE works with the guideline groups to ensure that the evidence cited and systematic reviews are of the highest quality and reviewed by experts in critical appraisal who have no competing interests. For drug and device recommendations, the highest level of evidence is required from randomized controlled trials of hard outcomes with adequate power and appropriate internal and external validity.7 Health behaviour change and diagnostic recommendations can have evidence with surrogate outcomes. Every effort is made to reduce the number of recommendations that are based on consensus opinion only, but these are still considered strong recommendations, as most people would follow the expert opinion where sufficient evidence does not exist. Drug and device recommendations are not based on consensus opinion. C-CHANGE aims to select recommendations based on high-quality evidence and to minimize recommendations that are based on consensus (8 of the 76 recommendations [10.5%] are consensus).

Box 2: 
### **Multifaceted care for patients with cardiovascular risk**

*   Healthy eating

*   Regular physical activity

*   Smoking cessation

*   Management of blood glucose

*   Control of blood pressure

*   Vascular-protective medications, including statins and blockers of the renin-angiotensin aldosterone system

### Major changes in recommendations

#### Hypertension

The Systolic Blood Pressure Intervention Trial (SPRINT) study, published in November of 2015, has led to substantial changes in blood pressure measurement and management recommendations in Canada and the United States.64,65 After SPRINT’s publication, a new category for hypertension for high-risk individuals was developed in Canada by Hypertension Canada with a new lower threshold for treatment (130 mm Hg systolic) and the lowest target blood pressure yet in any Canadian guideline (< 120 mm Hg systolic). This large National Institutes of Health study has excellent internal and external validity and showed that the lower blood pressure target offered a substantial cardiovascular benefit for higher-risk patients who had a systolic blood pressure of 130 mm Hg or more and the presence of a Framingham Risk Score of 15% or more, chronic kidney disease (estimated glomerular filtration rate [eGFR] 20–60 mL/min), or were aged 75 and older. The study did not include patients with diabetes or previous stroke, or those with postural hypotension, or who were unwilling to take intensified therapy. The results showed a relative risk reduction of cardiovascular events by 25% (95% confidence interval [CI] 0.64–0.89) and total mortality by 27% (95% CI 0.60–0.90) at only 3.3 years and associated numbers needed to treat of 62 and 90, respectively, over three years.65 The number needed to treat of the primary outcome over 3.14 years for participants aged 75 and older was 27, and for frail compared with fit participants, there was greater absolute benefit.66

The SPRINT study was also consistent with the recent Hypertension Canada change in recommendation on blood pressure measurement in the office.11 Automated oscillometric devices are now preferred over manual readings with aneroid or mercury sphygmomanometers, and home measurements or, preferably, ambulatory blood pressure monitoring are recommended for the diagnosis of hypertension.11,67–72 Measurement of blood pressure with automated devices in the waiting room and in the pharmacy has been shown to closely approximate home blood pressure monitoring, as well as daytime ambulatory blood pressure monitoring.73

Single-pill combinations are now recommended as initial therapy for patients with elevated blood pressure even less than 20/10 above target. The evidence comes from the improved adherence and efficacy of single-pill combinations and studies showing a reduction in cardiovascular events.74

#### Dyslipidemia

For management of dyslipidemia, the Canadian approach is a treat-to-target model. The Canadian Cardiovascular Society guideline for managing dyslipidemia in adults to prevent cardiovascular disease recommends pharmacologic therapy with statins for high-risk groups, including those with clinical atherosclerosis, abdominal aortic aneurysm, diabetes, chronic kidney disease, or low-density lipoprotein (LDL) cholesterol ≥ 5.0 mmol/L, as well as a Framingham Risk Score of ≥ 20%. However, for primary prevention, a risk assessment is required, as those with a risk score < 10% do not require pharmacotherapy, and a “fire-and-forget” strategy is inappropriate (i.e., treatment without follow-up blood tests to monitor lipid levels).

For those at intermediate risk, there is consideration of therapy based on other risk factors, such as an LDL ≥ 3.5, non–high-density lipoprotein (non-HDL) cholesterol ≥ 4.3, apolipoprotein B-100 ≥ 1.2, or men aged 50 years or older and women aged 60 years or older with one additional cardiovascular disease risk factor. These targets come from studies showing that achieving lower LDL levels was associated with better outcomes,75 that the proportional reduction of major cardiovascular events was directly related to the absolute LDL reduction with no evidence of a threshold,76 that better outcomes were seen with at least a 50% reduction in LDL,77,78 and that intensification of statin therapy was associated with better outcomes in patients with cardiovascular disease.39,79 The European Society of Cardiology80 and the American College of Cardiology81 have recommended the use of targets as well.

#### Diabetes

The assessment of diabetes now includes testing with a two-hour plasma glucose after a 75 g oral glucose tolerance test for people with glycosylated hemoglobin (A1c) levels from 6.0% to 6.4%. Reliance on A1c or fasting plasma glucose alone can miss impaired fasting glucose or impaired glucose tolerance82 and the oral glucose tolerance test is of benefit in patients with unexplained microvascular complications. It also helps to identify those who will benefit from a reduction in cardiovascular risk factors.83 Higher prevalence of hemoglobinopathies also reduce the accuracy of A1c in high-risk non-Caucasian ethnic groups.84

The management of type 2 diabetes has been expanded with two new medication classes, the sodium–glucose cotransporter 2 (SGLT2) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists, with some members of each class showing reductions in major cardiovascular outcomes in addition to blood glucose-lowering and, often, weight loss.85 An antihyperglycemic agent with proven cardiovascular benefit should be added to existing therapy to reduce cardiovascular outcomes.85 Addition of an SGLT2 inhibitor or a GLP-1 agonist is recommended for patients with uncontrolled diabetes and cardiovascular disease.

The current recommendation for an angiotensin-converting inhibitor or an angiotensin-receptor blocker in patients with diabetes is for patients older than 55 years who have one additional cardiovascular risk factor, or clinical cardiovascular disease or microvascular complications. This is a change from previous recommendations that all people with diabetes older than 55 years should be treated with a renin angiotensin-aldosterone system blocker, considering the lack of evidence for cardiovascular benefits in the lower-risk population.

#### Atrial fibrillation

The use of direct oral anticoagulants is recommended for non-valvular atrial fibrillation over warfarin, based on randomized controlled trials showing equal or greater reduction of stroke, equal or less major bleeding, less intracranial bleeding, and no net increase in coronary artery disease outcomes. We recognize that as yet there are no long-term data on the effect of new oral anticoagulants on coronary outcomes, in contrast to that for efficacy of warfarin.86

#### Health behaviours

Changes in recommendations regarding health behaviours include recognition that high sodium intakes (i.e., > 6 g/d) are associated with worse cardiovascular outcomes, particularly in people with hypertension.87 Avoiding a diet high in sodium and aiming for a total daily sodium intake toward 2 g (5 g of salt or 87 mmol of sodium) per day is recommended to lower blood pressure in people with hypertension and to prevent or delay the new onset of hypertension in those at risk.74 For dietary intake, maintaining sufficient calories for a healthy body weight and consuming a diet that is enjoyable and culturally appropriate is an overarching goal; when combined with regular physical activity, as outlined by the Canadian Society of Exercise Physiology guideline, diet can help to prevent type 2 diabetes.88

Cigarette smoking is a well-established risk factor for vascular disease. There is now sufficient evidence for recommendations for screening and advising on smoking cessation, as well as the use of pharmacotherapy for smoking cessation.89 Much of the evidence is summarized in a Cochrane collaboration systematic review finding that brief physician advice to stop smoking led to clinically important increases in smoking cessation, and advice combined with pharmacotherapy increased cessation rates over advice alone.27,90

## Implementation

Continuing professional development is an important method of disseminating guidelines to primary care practitioners. C-CHANGE’s electronic continuing professional development modules are hosted on the College of Family Physicians of Canada’s Prevention in Hand initiative website ([www.preventioninhand.com/Modules.aspx](http://www.preventioninhand.com/Modules.aspx)), and are accredited by the college and the Royal College of Physicians and Surgeons of Canada. C-CHANGE education modules facilitate small-group, case-based practice workshops; each is codeveloped by a member of the College of Family Physicians of Canada.

C-CHANGE supports the development of implementation tools for provincial and regional applications by asking these groups to include a guideline developer as part of the process, to ensure that the adaptation is true to the original recommendation and able to receive C-CHANGE endorsement.18

Patients often have multiple comorbidities, complicated by conditions such as stroke or myocardial infarction. A disease-silo approach to care leads to the risk of fragmentation, overlooking treatable risk factors. C-CHANGE helps to promote patient care by bringing guidelines from multiple groups together, formatted so that members of the interprofessional team can collaborate to formulate a comprehensive treatment plan directed to patient priorities. This makes it easier to achieve integration of primary and specialty care and to align this with the patient’s health outcome goals and preferences.91

The development of C-CHANGE guideline–based quality practice indicators, such as those in the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) study,92 allow for surveillance and evaluation of primary care practice behaviours and can inform the guideline development process about practice gaps, or recommendations that may not be able to be implemented. Ongoing “real-world” surveillance of practice changes recommended by the C-CHANGE guideline is important to identify where “practice gaps” exist and where guideline implementation efforts are most needed. Use of the set of quality indicators developed by the CANHEART initiative (based on previous versions of the C-CHANGE guideline) has shown that health regions in Ontario with better adherence to these guidelines have fewer cardiovascular events.92,93

The Triple Aim Framework offers a foundation for health care providers to conceptualize health care with an emphasis on optimizing health for individuals and populations, and the health care experience.94 This framework considers the patient experience of care, health of populations and per capita cost of health care, all of which need to be considered simultaneously. Leveraging the C-CHANGE harmonization of cardiovascular guidelines, the “real-world” surveillance of current practices and quality indicators and patient experiences, health care providers and decision-makers may assess, evaluate and identify opportunities for health care improvement across many patients with comorbidities, in alignment with this framework.

Telehealth interventions that include technologies (social networking services, smart phone applications, and patient and clinician portals) may enhance the remote delivery, support and monitoring of interventions reflective of C-CHANGE recommendations and quality indicators.95 With respect to the importance of healthy behaviours in preventing and managing cardiovascular disease, technologies may provide patients with asynchronous or synchronous access to feedback from health care professionals, while giving health care practitioners insightful patient data on healthy behaviours, medication adherence and other health goals. Technology preferences should be tailored to meet the needs of the patient and provider, as well as being integrated with electronic medical records.96,97

The next update of the C-CHANGE guideline is projected to be in 2021, dependent on sufficient changes in the existing recommendations, or sooner if warranted by new evidence that will substantially change primary care practice. During this time, C-CHANGE will provide feedback to the individual guideline groups on their recommendations.

## Other guidelines

Table 9 highlights some recommendations from other guidelines that differ from those included in this C-CHANGE update.

View this table:
[Table 9:](http://www.cmaj.ca/content/190/40/E1192/T9)

Table 9: 
National and international guidelines for the management of cardiovascular disease

## Gaps in knowledge

Obesity impairs health with respect to physical, mental and social well-being. We recommend the assessment and management of obesity using body mass index and waist circumference measurements as initial screening tools; however, these measures are based on Caucasians. Because body fat distribution varies with different ethnicity, different ethnicity-specific cut-points for body mass index and waist circumference may provide more accurate assessment of adiposity-related complications in specific populations.103

Other gaps include blood pressure measurement and treatment thresholds for home and ambulatory monitoring in people with diabetes, as well as the management of resistant hypertension.

## Conclusion

The C-CHANGE Initiative has resulted in a comprehensive set of recommendations that provide a single national authoritative source for the primary care management of cardiovascular disease. C-CHANGE shows that Canada’s national cardiovascular-focused guideline groups can produce rigorous harmonized recommendations that allow interprofessional teams to manage, collaboratively and confidently, Canadians who have and are at risk for cardiovascular disease. This set of recommendations can be implemented and disseminated to meet the regional needs of Canadians.

## Acknowledgements

The C-CHANGE executive (James Stone, Sheldon Tobe, Peter Liu, Diane Hua-Stewart and Kimberly Walker) acknowledges the insightful advice, wisdom and enthusiastic support of the following people who have contributed to the C-CHANGE process, the implementation or evaluation, and the 2018 update: Norman Campbell and Karen Tu; and for continuing professional development initiatives: David Dannenbaum, John Hickey, Thuy Pham, Sol Stern, Richard Ward and Sheila Hu. The executive also thanks Peter Jones and Alison Mulvale from the Ontario College of Art and Design University (OCADU) for designing the C-CHANGE guideline table in Appendix 1, and for using C-CHANGE for the Inclusive Health Design program (MDes) at OCADU.

## Footnotes

*   * Dr. Jack Tu, a member of the C-CHANGE guideline panel, died on May 30, 2018, during preparation of this manuscript for publication.

*   *CMAJ* Podcasts: author interview at [https://soundcloud.com/cmajpodcasts/180194-guide](https://soundcloud.com/cmajpodcasts/180194-guide)

*   **Competing interests:** Todd Anderson reports receiving grants from Amgen and DalCor, and personal fees from Sanofi, Merck, and Amgen, outside the submitted work. Alice Cheng reports personal fees from Abbott, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier and Takeda, outside the submitted work. Gord Gubitz reports receiving personal fees from Bayer, Pfizer and Boehringer Ingelheim, outside the submitted work. David Lau reports receiving research funding and speaker fees from AstraZeneca and Novo Nordisk and has received speaker fees and/or served as consultant from Amgen, Akcea, Boehringer Ingelheim, Janssen, Merck, Shire and Valeant, outside the submitted work. Lawrence Leiter has received research funding from, has provided CME on behalf of, or has acted as an adviser to Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion, GlaxoSmithKline, Janssen, Kowa, the Medicines Company, Merck, Novartis, Novo Nordisk, Resverlogix, Sanofi, Servier and The Medicines Company, outside the submitted work. Peter Selby reports receiving grants from Pfizer Inc., Bhasin Consulting Fund, Patient-Centered Outcomes Research Institute, Pfizer Canada Inc.; personal fees from Bristol-Myers Squibb, Pfizer Canada Inc., Evidera Inc., Johnson & Johnson Group of Companies, Medcan Clinic, Miller Medical Communications, NVision Insight Group, Myelin & Associates; and is a vendor of record for providing smoking cessation pharmacotherapy (free or discounted) for research studies for Pfizer, Novartis, Johnson & Johnson, and Med-Plan Communications, outside the submitted work. Simon Bacon has received consultancy fees from Schering-Plough, Merck and Sygesa, speaker fees from Novartis, and investigator-initiated grants from GlaxoSmithKline and Abb Vie. Sheldon Tobe reports grants from Eli Lilly, Astra Zeneca, AbbVie and Bayer, as well as personal fees from Servier and Valeant, during the conduct of the study. He has also had travel reimbursed by the Novartis Foundation. Sean Wharton reports personal fees from Novo Nordisk, Janssen and Eli Lilly, outside the submitted work. Eileen O’Meara reports clinical trial and national leader function fees paid to her institution from Novartis; clinical trial and national leader function fees paid to her instution, as well as consulting fees from Astra Zeneca; clinical trial fees paid to her institution from Merck; clinical trial fees paid to her institution and consulting fees from Bayer; and clinical trial and steering committee fees paid to her institution from Amgen. James Stone reports personal fees from Astra Zeneca, Bayer, Lilly, Sanofi, Novo-Nordisk and Servier, as well as personal fees for a clinical research trial from Sanofi, outside the submitted work. No other competing interests were declared.

*   **Contributors:** Sheldon Tobe wrote the first and subsequent versions of the manuscript. James Stone, Peter Liu, Kimberly Walker and Diane Hua-Stewart are the executive members of C-CHANGE; Todd Anderson, Simon Bacon, Alice Cheng, Stella Daskalopoulou, Justin Ezekowitz, Jean Gregoire, Gord Gubitz, Rahul Jain, Karim Keshavjee, Patty Lindsay, Mary L’Abbe, David Lau, Lawrence Leiter, Eileen O’Meara, Glen Pearson, Doreen Rabi, Diana Sherifali, Peter Selby, Mark Tremblay, Richard Ward and Sean Wharton are members of the C-CHANGE guideline panel. All members of the panel developed the 2018 C-CHANGE guideline, reviewed and made substantive contributions to the manuscript. All of the authors, with the exception of Jack Tu, approved the final version submitted for publication and agree to act as guarantors of the work.

*   **Funding:** Funding for the development of the 2018 C-CHANGE guideline was provided by the Canadian Vascular Network through a Canadian Institutes of Health Research Emerging Networks Grant (no. 132211). The C-CHANGE implementation tools and activities were funded by the Public Health Agency of Canada (no. 6464-15-201-8041132) and the Ontario Ministry of Health and Long-Term Care (no. 06668 and 0669). The funders did not have a direct influence on the process, the contents of the recommendations or the preparation of the manuscript.

*   **Endorsements:** Canadian Action Network for the Advancement, Dissemination and Adoption of Practice-Informed Tobacco Treatment (CAN-ADAPTT); Canadian Cardiovascular Society; Canadian Association of Cardiovascular Prevention and Rehabilitation; Canadian Society for Exercise Physiology; Diabetes Canada; Hypertension Canada; Obesity Canada; Heart and Stroke Foundation.

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