Canadian Cardiovascular Harmonized National Guideline Endeavour (C-CHANGE) guideline for the prevention and management of cardiovascular disease in primary care: 2022 update
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* Rahul Jain
* James A. Stone
* Gina Agarwal
* Jason G. Andrade
* Simon L. Bacon
* Harpreet S. Bajaj
* Brian Baker
* Gemma Cheng
* David Dannenbaum
* Mark Gelfer
* Jeffrey Habert
* John Hickey
* Karim Keshavjee
* Darlene Kitty
* Patrice Lindsay
* Mary R. L’Abbé
* David C.W. Lau
* Laurent Macle
* Michael McDonald
* Kara Nerenberg
* Glen J. Pearson
* Thuy Pham
* Alexandre Y. Poppe
* Doreen M. Rabi
* Diana Sherifali
* Peter Selby
* Eric Smith
* Sol Stern
* George Thanassoulis
* Kristin Terenzi
* Karen Tu
* Jacob Udell
* Sean A. Virani
* Richard A. Ward
* Darren E.R. Warburton
* Sean Wharton
* Jennifer Zymantas
* Diane Hua-Stewart
* Peter P. Liu
* Sheldon W. Tobe

KEY POINTS
*   This updated C-CHANGE guideline is a subset of recommendations chosen from guidelines from 11 of Canada’s cardiovascular-focused guideline groups, expanded to include Health Canada’s dietary guideline, the Canadian Consensus Conference on Diagnosis and Treatment of Dementia and the Canadian Cardiovascular Society/Canadian Heart Rhythm Society guideline for the management of atrial fibrillation.

*   The 2022 C-CHANGE update includes a total of 83 recommendations, of which 48 are new or revised.

*   Multifaceted care for patients with cardiovascular risk includes the cornerstones of health behaviour change: healthy eating, regular physical activity and exercise, healthy body weight, stress management, reduced alcohol intake and smoking cessation.

*   Cardiovascular disease prevention is foundational to primary care practice and incorporates appropriate risk screening and risk stratification.

*   Cardiovascular disease management combines guideline-directed health behaviour change and pharmacologic therapies to reduce symptoms, burden of disease, complications and residual cardiovascular risk.

The goal of the Canadian Cardiovascular Harmonized National Guideline Endeavour (C-CHANGE) process is to give all Canadian health care providers easy access to a comprehensive and practical set of harmonized guideline recommendations. Clinicians claim that there are too many guidelines with too many individual recommendations to be practical and accessible for primary care; that their patients’ multimorbidity requires them to access many guidelines at the same time; and that at least in the past, some of the recommendations were not harmonized and seemed contradictory.1

Established in 2008 to address these issues, C-CHANGE produces a guideline that is a subset of recommendations chosen from guidelines developed by Canada’s cardiovascular-focused guideline groups. It is designed to help clinicians formulate comprehensive treatment plans for use by all members of the health care team to address multimorbidity, as recommended by the *Canadian Heart Health Strategy and Action Plan*.2 This fourth update was necessitated by recent changes to the guidelines included in previous updates and the addition of guidelines from 3 guideline groups new to the C-CHANGE process (Canadian Cardiovascular Society/Canadian Heart Rhythm Society guideline for the management of atrial fibrillation, Health Canada’s Dietary Guideline and the Canadian Consensus Conference on Diagnosis and Treatment of Dementia) (Appendix 1, available at [www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content](http://www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content)), thus increasing the comprehensiveness from the 2011,1 20143 and 20184 versions to a total of 11 guideline groups.

The Global Burden of Diseases survey identified that the risk factors accounting for the largest percentage of disability-adjusted life-years in Canada included tobacco use, dietary factors, high body mass index (BMI), high fasting blood glucose, increased systolic blood pressure, elevated cholesterol, alcohol and drug use, and low physical activity.5 These risk factors frequently cluster, and their joint management is key for the prevention of and recovery from acute cardiovascular diseases, highlighting the need for a multimorbidity approach for chronic diseases. The importance of renewed attention to these risk factors is shown by the negative cardiovascular consequences of delayed treatment during the COVID-19 pandemic, heightening the importance of accessible, timely, equitable and comprehensive care.6

C-CHANGE specifically chooses implementable or actionable recommendations for primary care and helpful tools to organize how patient care is approached in clinic during periodic health and episodic visits (i.e., preventive strategies, screening, diagnostics and treatment). The recommendations are organized to address and individualize the management of patients with multiple comorbidities. This approach is inclusionary, nonjudgmental and unbiased, and focuses on the complexities of delivering comprehensive cardiovascular disease care in a primary care environment. Users of this guideline are encouraged to identify the individual root causes of cardiovascular risk and disease, complications and barriers to treatments, and to follow a patient-centred approach, including patient-identified health goals that incorporate the patient’s values.7 The C-CHANGE guideline also facilitates the discussion of treatment options beyond pharmacotherapy, including nutrition and physical activity, and procedural and psychological interventions.

## Scope

The goal of C-CHANGE is to assist health care providers in managing patients who often have multiple cardiovascular comorbidities, through the initiation and implementation of individualized atherosclerotic cardiovascular disease (ASCVD) risk reduction strategies, based on their expert knowledge of their patient’s preferences, goals and values. Although the main audience for this guideline update is primary care providers, many other specialists and members of the interprofessional team who manage patients with multiple cardiovascular disease comorbidities — such as atrial fibrillation, diabetes, hypertension, dyslipidemia, heart failure and obesity — may also find this guideline useful and relevant.

## Recommendations

Recommendations selected from the 11 included guidelines have been organized into 4 groupings. The recommendations are ordered to consider the progression of pathology, from primary prevention to the effects of comorbidities and other risk factors, to target organ damage. The first grouping describes health behaviours for all patients, with subsections for dietary, physical activity and exercise, and smoking cessation (Table 1). Recognizing that obesity underlies many of the cardiovascular risk factors discussed, recommendations on obesity are paired with the adiposity-related diseases of diabetes and hypertension (Table 2). Recommendations for people with dyslipidemia, ASCVD or heart failure are grouped together (Table 3), as are recommendations for those with atrial fibrillation, stroke or dementia (Table 4).

View this table:
[Table 1:](http://www.cmaj.ca/content/194/43/E1460/T1)

Table 1: 
C-CHANGE 2022 recommendations on health behaviours for all people

View this table:
[Table 2:](http://www.cmaj.ca/content/194/43/E1460/T2)

Table 2: 
C-CHANGE 2022 recommendations for people with obesity, diabetes or hypertension

View this table:
[Table 3:](http://www.cmaj.ca/content/194/43/E1460/T3)

Table 3: 
C-CHANGE 2022 recommendations for people with dyslipidemia, atherosclerotic vascular disease or congestive heart failure

View this table:
[Table 4:](http://www.cmaj.ca/content/194/43/E1460/T4)

Table 4: 
C-CHANGE 2022 recommendations for people with atrial fibrillation, stroke or dementia

Recommendations are clustered into subsections where appropriate for diagnostic strategies, treatment targets, and pharmacologic or procedural therapies. For each of the 83 recommendations (48 of which are new or revised), the source guideline is identified in conjunction with the strength of the recommendation and the level of evidence (Tables 1–⇑⇑4). As the guideline groups use different grading methodologies, the grading schemes are summarized in Appendix 2a (available at [www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content](http://www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content)), with a comparison of the different grading schemes used in the recommendations (Appendix 2b) and a summary of the details of the grade methodology (Appendix 2c). The supporting text highlights many of the important updates and new recommendations.

Recognizing the importance of depression in the management and prevention of ASCVD, we have included additional information that emphasizes this linkage and a pragmatic evidence-informed approach to depression management.

### Health behaviours applicable to all

Health behaviour change remains the foundation of the C-CHANGE guideline and should be prescribed to all individuals (Table 1). Health Canada’s Dietary Guideline recommends water as the preferred beverage of choice, avoiding sugar-sweetened beverages.8 The Global Burden of Diseases Nutrition and Chronic Diseases Expert Group found, for example, that individuals consuming 1 to 2 servings of sugar-sweetened beverages per day had a 26% greater risk of developing type 2 diabetes (risk ratio [RR] 1.26, 95% confidence interval [CI] 1.12 to 1.41) than those who consume less than 1 serving per month.21

Starting physical activity at any level compared with remaining inactive provides the greatest increment in health benefits, and there are important health benefits even at a lower volume or intensity of physical activity.22 For example, individuals active at half the current recommendations compared with inactive individuals (e.g., those reporting no leisure-time physical activity) still had a 14% lower risk of coronary artery disease (RR 0.86, 95% CI 0.76 to 0.97).23 Therefore, rather than aiming for the maximal amount from the start, clinicians should target any physical activity or exercise that patients are willing to begin, supporting them to generate solutions to perceived barriers.24 In the presence of disabilities that prevent exercise at a moderate or vigorous level, clinicians should recommend physical activity at a lower level that is comfortable and, over time, encourage longer duration and increased frequency.

For people with obesity, a pooled meta-analysis showed that an average of 46 minutes of walking 4 times weekly at a moderate intensity over 12 to 16 weeks led to overall weight loss of 2.13 kg (95% CI −3.2 to −1.06), a reduction of BMI by 0.96 kg/m2 (95% CI −1.44 to −0.48) and a reduction in waist circumference of 2.83 cm (95% CI −4.13 to −1.53). A subgroup analysis on women older than 50 years who did not lose weight still found that physical activity was associated with an improvement in waist circumference resulting from an increase in fat-free mass.25

### People with obesity, diabetes or hypertension

Recommendations for people with obesity, diabetes or hypertension are outlined in Table 2. Obesity is now recognized as a chronic disease. In the health care setting, weight bias among providers reduces quality of care and can be identified with self-assessment tools.12 The development of personalized management plans is facilitated by understanding an individual’s context and culture and integrating these with the root causes of their obesity.12

The pillars of obesity therapy include behavioural and psychological interventions, pharmacotherapy and bariatric surgery. Medical therapy to aid with weight loss is now effective and safe, and may include the glucagon-like peptide-1 (GLP1)-receptor agonists. In a randomized controlled trial, adults with a BMI of at least 30 kg/m2, or 27 kg/m2 with comorbidities, and who were able to take liraglutide over the 3-year study period, lost weight and developed new diabetes more slowly (2.7 times longer [95% CI 1.9 to 3.9]) than those on placebo.26 Bariatric surgery has been shown to be effective for treating obesity. A network analysis showed that a Roux-en-Y gastric bypass improved BMI at 2 years, with a mean difference of −7.2 kg/m2 (95% CI −8.9 to −5.5).27 Weight loss leads to improvement in other adiposity-related risk factors.28

A major change in the management of diabetes since the 2018 C-CHANGE update is the new evidence showing cardiovascular risk reduction for GLP1 receptor agonist and sodium–glucose cotransporter 2 (SGLT2) inhibitor classes: for both classes in reducing major adverse cardiovascular events (MACE), and for SGLT2 inhibitor drugs in reducing heart failure resulting in hospital admission and progression of nephropathy. The previous recommendation for using these agents to treat people with diabetes and ASCVD was changed in this 2022 update to include primary prevention for those aged 60 years and older with 2 or more cardiovascular risk factors such as tobacco use, dyslipidemia or hypertension, in conjunction with the removal of the requirement for uncontrolled glycosylated hemoglobin (HbA1c).

The Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) study enrolled patients with type 2 diabetes and an HbA1c of 7% or greater with ASCVD if they were aged 50 years or older, and if 60 years or older, patients could have only 1 cardiovascular risk factor, such as abnormal albuminuria, hypertension and left ventricular hypertrophy or peripheral vascular disease.29 After a median follow-up of 2.1 years, for the primary composite outcome of MACE, there was a 26% relative risk reduction with use of semaglutide (hazard ratio [HR] 0.74, 95% CI 0.58 to 0.95; number needed to treat [NNT] 44).

The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial enrolled participants with type 2 diabetes; 68.5% of participants had at least 2 cardiovascular risk factors and no previous cardiovascular events (primary prevention). 30 After a median follow-up of 5.4 years, there was a lower incidence of MACE with dulaglutide than with placebo, with a 12% relative risk reduction (HR 0.88, 95% CI 0.79 to 0.99; NNT 71).

Most of those (59%) enrolled in the Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes (DECLARE-TIMI 58) trial had cardiovascular risk factors only. After a median follow-up of 4.2 years in this predominantly primary prevention cohort, the incidence of MACE was not significantly improved, but there was a reduction in hospital admissions for heart failure of 27% (HR 0.73; 95% CI 0.61 to 0.88; NNT 43), and a reduction in progressive kidney disease of 24% (HR 0.76 95% CI 0.67 to 0.87; NNT 71).31

In patients with diabetes and advanced nephropathy, the Canagliflozin and Renal End Points in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study found a 30% relative risk reduction in the main renal composite outcome (renal or cardiovascular death, dialysis or doubling of creatinine) with canagliflozin (HR 0.70, 95% CI 0.58 to 0.82; NNT 22), as well as significant improvements in MACE, including hospital admissions for heart failure.32 Cardiovascular and renal data showing similar protection in people with diabetes with empagliflozin confirm the class effect.33,34

Follow-up of patients who receive a diagnosis of hypertension and who are actively working on changing their health behaviours is recommended every 3 to 6 months. When antihypertensives are being adjusted to bring the blood pressure to target, patients should be followed up within 8 weeks, with shorter intervals if the patient is at higher cardiovascular risk.9 People with 1 adiposity-related comorbidity, such as diabetes and hypertension, should be screened for other related risk factors.35

### People with dyslipidemia, atherosclerotic vascular disease or congestive heart failure

Recommendations for people with dyslipidemia, ASCVD and congestive heart failure are summarized in Table 3. Acute myocardial infarction (MI) is associated with individual risk factors; data collected from virtually every country in the world show that risk of MI triples with current smoking or diabetes, and the risk doubles with hypertension, obesity, depression or dyslipidemia.36

Prevention of new ASCVD with statins is effective in people at intermediate risk (men aged 55 yr or older and women 65 yr or older, with at least 1 of elevated waist–hip ratio; low high-density lipoprotein; history of smoking; dysglycemia; family history of premature coronary disease; abnormal albuminuria; or estimated glomerular filtration rate < 50 mL/min). In the Heart Outcomes Prevention Evaluation–3 (HOPE–3) study, cholesterol-lowering with rosuvastatin 10 mg/d reduced the composite of cardiovascular death, nonfatal MI or stroke by 24% (HR 0.76, 95% CI 0.64 to 0.88; NNT 91), compared with placebo.37

The role of acetylsalicylic acid (ASA) for primary prevention continues to be downgraded, with the removal of the recommendation for its use in primary prevention for patients with hypertension aged 50 years and older.9 The Diabetes Canada recommendations added a “should not” recommendation for the use of ASA for primary prevention of ASCVD in people with diabetes.14 The recommendation for use of ASA for secondary prevention remains and is supported by strong evidence.38

The management of dyslipidemia now emphasizes a foundation of health behaviour change, with the addition of statins to lower low-density lipoprotein-C (LDL-C) below the risk-appropriate thresholds.16 For most patients in whom statins are indicated for primary prevention of ASCVD events, the threshold is an LDL-C level less than 2.0 mmol/L. For the use of statins in secondary prevention (i.e., patients with established ASCVD), the threshold is now an LDL-C level of 1.8 mmol/L. If the LDL-C is not lowered below either 2.0 or 1.8 mmol/L on maximally tolerated statin, for primary and secondary prevention, respectively, this is an indication for intensification of therapy beyond statins, including the addition of ezetimibe or PCSK9 inhibitors or both. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) study tested the PCSK9 inhibitor evolocumab compared with placebo in patients with LDL 1.8 mmol/L or higher with ASCVD on statin (5% were also taking ezetimibe).39 At 48 weeks, there was a 15% reduction in risk of cardiovascular death, MI, stroke, hospital admission for unstable angina, or coronary revascularization (HR 0.85, 95% CI 0.79 to 0.92; NNT 67).39

The management of heart failure has substantially changed. A decision-analytic model showed that the all-cause mortality for patients with heart failure and reduced ejection fraction was 35% at 24 months without evidence-based therapy, dropping to 10% with the cumulative benefit of quadruple therapy.40 Quadruple therapy comprises angiotensin receptor antagonist neprilysin inhibitors, β-blockers, mineralocorticoid receptor antagonists and SGLT2 inhibitors. The challenge now is to initiate and titrate these therapies expeditiously using goal-directed medical therapy. Most current treatment recommendations are relevant to patients with established heart failure with reduced ejection fraction. However, nearly half of all patients with heart failure have preserved or mildly reduced ejection fraction, and future guidance based on new evidence will likely reflect updated evidence for managing this subgroup of patients.

### People with atrial fibrillation, stroke or dementia

The recommendations for people with atrial fibrillation, stroke or dementia are outlined in Table 4. Atrial fibrillation is a major risk for stroke and is estimated to be prevalent in 1.4% of people older than 65 years.19 However, a prospective cohort study of 2171 patients aged 65 or older in Canadian primary care practices found that 2.7% had atrial fibrillation.17 Stroke caused by atrial fibrillation is disabling in 60% of people and fatal in 20%.18 Oral anticoagulation with warfarin reduces stroke from nonvalvular atrial fibrillation by 60% compared with placebo and 20% for antiplatelet therapy alone.19 The new direct-acting oral anticoagulants have shown better efficacy, with equal or better safety, than warfarin and are now recommended over warfarin for patients with nonvalvular atrial fibrillation. A meta-analysis of the 4 direct-acting oral anticoagulants available in Canada (apixaban, dabigatran, edoxaban and rivaroxaban) showed a reduction of a composite of stroke and systemic embolism (RR 0.81, 95% CI 0.73 to 0.91), as well as less major bleeding (RR 0.85, 95% CI 0.73 to 1.00), than warfarin.41

For patients who survive a stroke, clinicians must also recognize that 20%–50% of affected people will also experience poststroke depression and anxiety, vascular cognitive impairment and poststroke fatigue.20 Dementia usually has a vascular contribution from stroke and hypertension.41 Screening for dementia is indicated if there is a clinical concern for a cognitive disorder or a history of stroke or transient ischemic attack, and should include an objective assessment of cognition and functional impairment. 20 A 4-item subset of the Montreal Cognitive Assessment, including clock drawing, tap-at-letter-A, orientation and delayed recall, was assessed in 8773 participants aged 65 years or older and was able to distinguish dementia from nondementia using an optimal cut-off score of < 10, with 87.9% sensitivity and 87.6% specificity.42

### Depression and cardiovascular health

Comorbidity screening for people with or at risk for ASCVD should include depression, as mood disorders may be present in about a quarter of older adults.42 Depression also has a direct impact on cardiovascular outcomes and management.43

In the absence of Canadian recommendations addressing depression and cardiovascular disease, and the request from the C-CHANGE patient panel to address depression, this subsection of the guideline has been added to reinforce the importance of depression as both a risk factor for the development of ASCVD and for worse outcomes, including mortality in patients with established ASCVD. We drew on the Scientific Statements from the American Heart Association and the European Society of Cardiology Working Group on Coronary Pathophysiology and Microcirculation.43–46 The recommendations for screening, referral and treatment of depression in people with ASCVD in the American Heart Association statements were endorsed by the American Psychiatric Association.43

About 1 in 6 with ASCVD have a major depressive disorder and a greater proportion have depressive symptoms.43,44,46 The interaction of depression with ASCVD is bidirectional, related to biological and psychological factors.44 Raising awareness of the adverse effects of depression on ASCVD outcomes may improve patients’ adherence to positive health behaviours, including medication use.44,46

Treatment for moderate to severe depression includes selective serotonin reuptake inhibitor antidepressants, such as sertraline or escitalopram (with occasional prolonged QTc effects);44,46 psychological treatments, such as stress management and cognitive behavioural therapy;44,46 and exercise and participation in cardiac rehabilitation programs.44,46 Mindful meditation is a useful adjunct in dealing with mood and ASCVD risk factors.44,46 A screening approach for all at-risk individuals and patients with ASCVD using the Patient Health Questionnaire-2 can be considered and, if positive, clinicians should be prepared to manage or appropriately refer those found to be depressed.43,44,46

## Methods

The C-CHANGE guideline update is developed by a volunteer guideline panel with expertise in guideline development, dissemination, implementation and evaluation. Quality assurance in guideline development is supported by the Appraisal of Guidelines, Research and Evaluation instrument (AGREE II).47,48

Recommendations included in C-CHANGE guidelines are drawn from guideline recommendations recently published by partner guideline groups and selected by the C-CHANGE Guideline Panel using a modified Delphi process.49 We added 3 guideline groups for this cycle (for a total of 11 guideline partners), as their recent guidelines were appropriate for C-CHANGE and each scored highly on the AGREE II checklist:48 the Canadian Cardiovascular Society/Canadian Heart Rhythm Society guideline for the management of atrial fibrillation, Health Canada’s Dietary Guideline and the Canadian Consensus Conference on Diagnosis and Treatment of Dementia guideline.8,19,20

### Composition of participating groups

Three main groups were involved in the development of this update: the C-CHANGE Executive (R.J., S.T, J.S., P.L., D.H.-S.), the C-CHANGE Guideline Panel and the Community Consultation and Review Panel (Appendix 1). The guideline panel included the leads or committee chairs from each of the 11 partner guideline groups; a multidisciplinary and interprofessional group of experts in their respective specialties; and sufficient primary care practitioners to make up a majority of the panel. Members of the Scientific Planning and Review Committee for the Canadian Cardiovascular

Health Education Program (CHEP+) were also invited to participate on the guideline panel (Appendix 1). The executive was tasked with finding primary care physicians to participate on the guideline panel and with vetting potential guideline panellists. The development and role of the Community Consultation and Review Panel are discussed in the Patient Engagement subsection.

### Guideline development

Updates for C-CHANGE guidelines are initiated when the C-CHANGE Executive meets with existing and new partner guideline groups and leads from these groups identify that there is sufficient new material to warrant an update. All relevant guidelines from the participating guideline groups considered for inclusion in the C-CHANGE process undergo an AGREE II assessment (D.H.-S.) to ensure academic rigour and appropriateness.

The development process for this update is summarized in Appendix 8 (available at [www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content](http://www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content)). For this update, the executive reviewed recommendations from the 2018 C-CHANGE guideline4 in conjunction with the leads from each partner group, for potential updates to individual recommendations and to identify recommendations targeted for removal. Furthermore, the executive reviewed all new guidelines from the groups, focusing on potential new recommendations that were directed toward primary care practice.

C-CHANGE uses a modified Delphi ranking process to select the final recommendations.49 The executive instructed guideline panel members that their role in the ranking process was vital to ensure recommendations chosen are relevant, implementable and of high impact in primary care. To ensure that all guideline panel members understood their role, role summaries were provided, along with online group presentations with question-and-answer periods (repeated as needed), so that all panellists became familiar with the information. All guideline panel members had the same role and a single vote.

The executive asked guideline panel members to consider the impact of attempting to be comprehensive by adding many recommendations from each guideline group; instead, they were instructed to choose only those recommendations that would have the highest impact in primary care for patients with multimorbidity, thereby leading to a smaller, more pragmatic subset of recommendations. It is a concern that for patients with multimorbidity, following the Chronic Care Model may increase the patient’s treatment burden (i.e., the impact of health care on patient well-being) through the addition of more treatments, testing and health care visits.50 Increased treatment burden has been associated with nonadherence, particularly in patients with more adverse social determinants of health.50 An insight from the concept of treatment burden in patients with multimorbidity and adverse social determinants of health is that nonadherence to prescribed therapy may be, in part, beyond the patient’s control.

The executive instructed panellists that C-CHANGE prefers the strength of included recommendations to be strong, usually with wording “we recommend,” indicating for clinicians that most patients should receive the recommendation, and that for patients, most people in that situation would want the recommended course of action.50 To limit bias, we excluded recommendations based upon low-quality evidence unless they had a strong clinical impact, as suggested by partnering guideline leads — such as the use of loop diuretics in heart failure.

For this update, C-CHANGE used a pool of more than 200 recommendations for the first round of the ranking process. Because of the pandemic, meetings of the guideline panel took place by videoconference, with multiple meetings from June 2021 to September 2021, to ensure that everyone was able to participate. Voting templates on Excel spreadsheets were emailed to panel members for the voting rounds.

The voting process we used was adapted from the Hypertension Canada guideline process.51 Existing recommendations (or their updated versions) from the 2018 guideline required support from 70% of those voting to remain. New recommendations required a ranked score of at least 7 out of 10, to get to the second round of voting. In the second round, recommendations from 2018 with 70% voting to remain, and new recommendations with a minimum score of 7, were voted on to stay or to go, with a minimum of 80% of votes to keep a recommendation in this round. This led to the final set of recommendations, which we shared with the guideline panel members for final comments.

In the C-CHANGE guideline, we have preserved the original wording and grade of each recommendation from the original partner guideline. The strength of the quality of evidence supporting the recommendation is also described. An overview of the grading schemes is available in Appendix 2b. Readers are referred to each specific guideline group website for additional details on the grading scheme and for the literature review supporting each recommendation (Appendix 2a).

We did not perform economic evaluations, given the absence of robust, high-quality health economic evidence. C-CHANGE emphasizes the importance of guideline users making management decisions appropriate to the clinical circumstances and resource realities within their own jurisdiction or region.

We passed on feedback on recommendations assessed during the modified Delphi process, but not included in this guideline, to partnering guideline groups for their individual quality improvement processes.

### Patient engagement

To reflect the patient voice, from ASCVD prevention to disease management, patient engagement for C-CHANGE took place in 3 phases. Before the C-CHANGE process, each guideline group had its own patient engagement process (more details available on each guideline group’s website; see Appendix 2a). A member of the C-CHANGE executive (D.H.-S.) evaluated these processes as part of the AGREE II evaluation for each guideline group; the evaluation of the guidelines’ patient-engagement processes can be found on the C-CHANGE website ([www.cchangeguidelines.com](http://www.cchangeguidelines.com)).

After the modified Delphi process described above, C-CHANGE, working with the Canadian Stroke Best Practices Group, brought together 10 people in a Community Consultation and Review Panel (CCRP) to ensure that the patient and caregiver voice was included and the principles of equity, diversity and inclusion52 endorsed and respected. The lived experience of the CCRP members (including persons with specific cardiovascular conditions and expert caregivers, defined as a person with sufficient lived experience and knowledge of the condition to meaningfully contribute to the CCRP; i.e., not a community health personal health worker who is not assigned permanently to that person) provided feedback and insights based on personal experiences. The inclusive nature of this group helped to ensure that the process and recommendations were grounded in real life experiences that directly reflected patients’ needs and preferences. We requested specific feedback from the CCRP with respect to how they viewed the C-CHANGE process and its potential impact on their own primary health care provider. The patient engagement interview guide and some representative quotes are found in Appendix 9 (available at [www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content](http://www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content)).

During the implementation process after the 2018 C-CHANGE guideline,4 we sought patient voices through focus groups, and key informant interviews conducted with the Ontario College of Art and Design University (OCADU) Health Design unit. This process was reinitiated in partnership with OCADU for this 2022 guideline.

### Management of competing interests

C-CHANGE follows the principles of the Guidelines International Network for guidance regarding the disclosure and management of competing interests throughout the guideline process (Appendix 10, available at [www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content](http://www.cmaj.ca/lookup/doi/10.1503/cmaj.220138/tab-related-content)).53,54 Guideline panel members with competing interests represented only a minority of the panel (9 of 40 panel members). Those with competing interests were instructed to recuse themselves from voting on recommendations that could be influenced by these competing interests. Using the voting templates, recommendations for therapies associated with potential competing interests in panel members were cross-tabulated to ensure that recommendations continued to meet the designated voting approval thresholds. Before the voting process, we collected a completed International Committee of Medical Journal Editors disclosure of interest form from each panel member (these forms are available on the C-CHANGE website at [https://www.cchangeguidelines.com/](https://www.cchangeguidelines.com/)).55

Partner guideline groups addressed potential competing interests individually in developing their source guidelines, but all scored well on the C-CHANGE AGREE II assessment. Additional information is available from each group’s website (Appendix 2a).

## Implementation

C-CHANGE is involved in both dissemination and implementation strategies of its guidelines through its knowledge translation arm, CHEP+. Activities include an annual national conference with plenary speakers representing chairs of partnering guideline groups, as well as interactive case-based workshops accredited by the College of Family Physicians of Canada and the Royal College of Physicians and Surgeons of Canada, designed to help practitioners change their practice behaviours. At the provincial level, C-CHANGE will approach ministries of health to promote regional programs and propose workshops at national and provincial primary care meetings. C-CHANGE’s publications and updates are posted on its website ([https://www.cchangeguidelines.com/](https://www.cchangeguidelines.com/)) and CHEP+ events and resources are posted on its website ([https://www.chepplus.com/](https://www.chepplus.com/)).

C-CHANGE supports partner guideline groups in guideline development and dissemination based on specific feedback on the implementability of individual recommendations, knowledge translation tools for clinicians such as outpatient flowsheets, and patient-oriented tools.

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 Cardiovascular Health in Ambulatory Care Research Team (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 better cardiovascular disease outcomes.56

We project that the next update of the C-CHANGE guideline will be in 2025, depending 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 continue to provide feedback to the individual guideline groups on their recommendations and implementation strategies.

## Other guidelines

Internationally, guideline groups that regularly update their recommendations seem to be coming closer together than farther apart. Blood pressure targets for high-risk patients (e.g., older [> 75 yr], with chronic kidney disease, at high cardiovascular risk) continue to fall based on the Systolic Blood Pressure Intervention Trial (SPRINT).57 The latest example is the Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure in people with chronic kidney disease, with a systolic blood pressure target lower than 120 mm Hg for patients with or without diabetes.58 This contrasts with C-CHANGE, in which the target systolic blood pressure for patients with diabetes (with or without chronic kidney disease) is still lower than 130/80 mm Hg and, for people with chronic kidney disease alone, lower than 120 mm Hg systolic. The KDIGO guideline developers decided to target a lower blood pressure for people with chronic kidney disease with or without diabetes to improve implementability, at the cost of weakening the evidentiary strength of recommendation. Table 5 highlights recommendations from other countries’ guidelines that differ from those included in this C-CHANGE update.

View this table:
[Table 5:](http://www.cmaj.ca/content/194/43/E1460/T5)

Table 5: 
National and international guidelines for the management of cardiovascular disease

## Gaps in knowledge

Managing patients with multimorbidity is increasingly complex and requires increased health care utilization.66 In patients with adverse social determinants of health, layering additional therapies for multimorbidity may worsen adherence in the most vulnerable by increasing their treatment burden.67 Health care practitioners need to understand better how to calibrate treatments to meet both public health and patient health needs.

Hypertension control rates in Canada were among the highest in the world up to 2010, and these rates were associated with improved national ASCVD outcomes.68 These rates of hypertension control and improved national outcomes were attributed in part to implementation projects such as continuing professional development programs leading to a more educated and integrated health care community.69 More recently, however, hypertension control rates in women have fallen.70 Although the specific reasons for this reduction are unknown, explanations include the loss of federal government support for hypertension surveillance, a fall in hypertension guideline implementation efforts, and the loss of industry sponsorship for education initiatives as generic medications have become more widely used.71 Importantly, in the effort to understand why ASCVD outcomes worsen in any population, there is a paucity of data on the effectiveness of specific interventions to implement clinical practice guidelines and their effect on improving ASCVD patient outcomes.

How to implement physical activity recommendations at the individual, family and community level, leading to observable change nationally in health and wellness, requires much greater attention. Implementing physical activity and exercise recommendations is often done in a manner implying that failure to achieve some threshold will not allow the health benefits to accrue; Warburton and Bredin advocate a strengths-based approach in health and wellness promotion that focuses on the innate strengths of individuals, families and communities.72 This approach has been increasingly used in Indigenous communities, including helping to build cultural competencies and culturally safe places.72 The greatest relative benefits of physical activity come from doing some activity, rather than remaining sedentary.22

## Limitations

This document is not a replacement for reading the individual guidelines. The C-CHANGE guideline is limited by the published literature, which is then evaluated for inclusion by individual guideline groups, and C-CHANGE must wait until the new evidence finds its way into its partners’ guidelines. The C-CHANGE process tries to balance comprehensiveness with the risk of missing some recommendations that different partner groups felt were important. There is no adjustment of the original wording of the source recommendations within the C-CHANGE process; wording suggestions for future guideline recommendations are provided as feedback to partner guideline leads for potential incorporation in their next guideline development cycle.

## Conclusion

C-CHANGE continues to meet its mandate from *The Canadian Heart Health Strategy and Action Plan* for guideline harmonization, expanding to 11 of Canada’s cardiovascular-focused guideline groups to produce an implementable and actionable guideline to help address and individualize the cardiovascular management of patients with multimorbidity. We made purposeful efforts to engage patients throughout the C-CHANGE process in an integrated and meaningful way. Our approach strives to respect the principles of equity, diversity and inclusion and focuses on the delivery of comprehensive cardiovascular health and disease care in a primary care environment. C-CHANGE provides a uniquely Canadian platform to engage health care providers in improving their guideline-directed best practices, with the goal of improving patient health outcomes.

## Acknowledgements

The authors acknowledge the participation of Health Canada’s Office of Nutrition Policy and Promotion in this work. The authors thank the Canadian Stroke Best Practices Group, led by Patrice Lindsay and their Community Consultation and Review Panel for their collaboration in leading the patient engagement process. They also acknowledge Rebecca McGuff from Stroke Best Practice Project, Heart & Stroke Foundation for her support and coordination in this process, and for our patient/caregiver panel members: Wendi Bacon, Wendi Plets, Janice Forsythe, Dianna Rasing, Wendy Reaser, Geri Rockstein, Wayne Sandvik and Helen Su for their invaluable feedback and insights from a patient/caregiver perspective. The authors thank the Ontario College of Art and Design University’s Health Design unit, led by Dr. Peter Jones, for their work on implementation efforts, particularly, the student members — Leah Ferguson, Carley MacAdam-Thompson, Hannah Walsh, Beverley Freedman, Rosa Chu and Maizie Lovatt — for their insights and expertise on aspects of health design on C-CHANGE implementation projects. They also thank Dr. Peter Jones and Rosa Chu for their collaborative design work on the final tables. The authors thank the Canadian Institutes of Health Research for funding support.

## Footnotes

*   **Competing interests:** James Stone reports receiving consulting fees and honoraria from Bayer Canada and Sanofi Canada. Dr. Stone is senior medical director, Cardiovascular Health and Stroke Strategic Clinical Network, Alberta Health Services; and member at large, Governing Council, College of Physicians and Surgeons of Alberta. Jason Andrade reports receiving payment or honoraria from Medtronic, Biosense-Webster, Abbott, Bio-tronik, Bayer, Servier and BMS-Pfizer. Simon Bacon reports receiving grants from Moderna, paid through Respiplus for the development of vaccine hesitancy education modules, and consultancy and speaker fees from Respiplus. Dr. Bacon has served on advisory boards for Bayer, Sanofi, Respiplus and Lucilab, none of which are related to the current article. Dr. Bacon also holds a Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research Mentoring Chair (SMC-151518) and Fonds de recherche du Québec Chair (251618 and 309815). Harpreet Bajaj reports receiving grants from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sanofi and Tricida; and honoraria for lectures from Eli Lilly and Novo Nordisk. Mark Gelfer reports receiving consulting fees from Telus Health Care Centres and holding an unpaid role as board chair of GenXys Health Care Systems, in which Dr. Gelfer also holds stock options. Jeffrey Habert reports receiving consulting fees from MDBriefcase, Liv, MedPlan, Master Clinician Alliance, Academy, Bridge, Seacourses, Thrombosis Canada, Meducom, Antibody, the Canadian Heart Research Centre, CTC Communications, STA Healthcare Communications, Canadian Collaborative Research Network, CPD Network, Telus Health, EOCI Pharmacomm and Operatic. Dr. Habert has also received honoraria from Pfizer, Amgen, BMS, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Purdue, Bausch, Allergan, AbbVie, AstraZeneca, Novartis, Lundbeck, Canadian Cardiovascular Health Education Program (CHEP+), Novo Nordisk, Janssen, Eisai, HLS, Otsuka, Sunovion and Jazz. Dr. Habert was the previous co-chair of the Thrombosis Canada Clinical Guides (2018–2021). Karim Keshavjee reports receiving consulting fees from McMaster University, Demers Professional Corporation and Normative. Darlene Kitty reports receiving teaching stipends from the University of Ottawa Faculty of Medicine and the McGill University Faculty of Medicine for occasional lectures, and travel support as director for the Indigenous Program of the University of Ottawa Faculty of Medicine. Dr. Kitty is the chair of the Indigenous Health Committee, College of Family Physicians of Canada. David Lau reports receiving grants from Novo Nordisk; consulting fees from Amgen, Bayer, Boehringer Ingelheim, CME at Sea, HLS Therapeutics, Eli Lilly, Novo Nordisk and Viatris; honoraria from Amgen, Bayer, Boehringer Ingelheim, CME at Sea, HLS Therapeutics, Eli Lilly and Novo Nordisk; and payment for expert testimony from the Canadian Medical Protective Association. Dr. Lau has served in leadership roles with Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons. Laurent Macle reports receiving grants and honoraria from BMS-Pfizer, Servier and Bayer. Michael McDonald reports receiving consulting fees from Boehringer Ingelheim, and honoraria from Novartis and Servier. Dr. McDonald also participated in the data safety monitoring board for the IVVE Trial. Kara Nerenberg reports membership with the clinical practice guideline committees for the Heart and Stroke Foundation, Obesity Canada, Hypertension Canada, Diabetes Canada and the Society of Obstetricians and Gynaecologists of Canada. Glen Pearson reports receiving consulting fees from Novartis Canada as an advisory board participant. Alexandre Poppe reports receiving a research grant from Stryker and an honorarium from Pfizer-BMS. Dr. Poppe has also participated on a data safety monitoring board for the FLOW trial of fluoxetine after stroke and the safety committee for the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT trial) of tenecteplase for acute stroke. Dr. Poppe has received fellowship program support from Servier. Diana Sherifali reports receiving personal funding through her Heather M. Arthur Population Health Institute/Hamilton Health Sciences Chair in Interprofessional Health Research. Peter Selby reports receiving grants from the Ontario Ministry of Health and Pfizer (Global Research Awards for Nicotine Dependence). Dr. Selby has also participated on the C-CHANGE guideline panel since 2010. Eric Smith reports receiving consulting fees from Bayer, Biogen, Alnylam and Cyclerion. Sol Stern reports receiving consulting fees and honoraria from [MDBriefcase.com](http://MDBriefcase.com) and Sea Courses Inc. George Thanassoulis reports receiving grants, consulting fees and honoraria from Amgen, Sanofi, Novartis and Silence. Dr. Thanassoulis has also been a member of the CCS Dyslipidemia Guideline committee. Kristin Terenzi reports receiving consulting fees for advisory boards of, honoraria for speaking events for, and support for attending meetings from AstraZeneca, Boehringer Ingelheim, Astellas, Allergan, Amgen, Aspen, Bayer, Lilly, Lundbeck, AbbVie, Aralez, GSK, Merck, Novo Nordisk, Pfizer and Novartis. Karen Tu reports receiving grants (payments to institution) from CIHR, St. Michael’s Hospital Foundation, The College of Family Physicians of Canada, Foundation for Advancing Family Medicine, Canadian Medical Association Foundation, North York General Hospital Exploration Fund, Heart and Stroke Foundation of Canada, Heart and Stroke Foundation of Ontario, United States Department of Defense, University of Toronto — Department of Family and Community Medicine, MaRS Innovation Fund, Canadian Dermatology Foundation, Canadian Rheumatology Association (Canadian Initiative for Outcomes in Rheumatology Care), PSI Foundation, Cancer Care Ontario, Toronto Rehab Institute Chair Fund, UTOPIAN, Arthritis Society, MS Society of Canada, The Canadian Vascular Network, Ontario SPOR Support Unit Targeted IMPACT Award and Rathlyn Foundation. Dr. Tu holds a Research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. Jacob Udell reports receiving grants from Boehringer Ingelheim, Janssen, Sanofi and Novartis; and honoraria from AstraZeneca, GlaxoSmithKline and Sanofi. Dr. Udell has also participated on advisory boards for Boehringer Ingelheim, Sanofi and Novartis. Sean Virani reports receiving grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Servier, Otsuka and Medtronic; consulting fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Seriver and Otsuka; and honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bayer, Novartis, Servier, Otsuka and Medtronic. Dr. Virani has also participated in data safety monitoring boards or advisory boards for Abott and Medtronic. Richard Ward reports receiving consulting fees from Eisai and Lilly-Boehringer Ingelheim, and payment or honoraria from Boehringer Ingelheim, AstraZeneca, Janssen, Amgen, Lilly, Pfizer and Takeda. Dr. Ward also serves as director of the Alberta Medical Association. Sean Wharton reports receiving grants and honoraria from Novo Nordisk, Eli Lilly, Bausch Health Canada and Boehringer Ingelheim; has participated in data safety monitoring boards for Novo Nordisk, Eli Lilly, Bausch Health Canada and Boehringer Ingelheim; and has received equipment, medical writing or other services from Novo Nordisk, Eli Lilly and Bausch Health Canada. Dr. Wharton has also played a leadership role in The Obesity Society and Obesity Canada. Jennifer Zymantas reports receiving an honorarium from Pfizer for a moderator role during speaking engagements related to anticoagulation. Diane Hua-Stewart holds the role of director of CHEP+. Peter Liu reports receiving grants from Genome Canada, the Heart and Stroke Foundation and CIHR. Dr. Liu holds a patent for IGFBP7 as a biomarker for heart failure and is chief scientific officer with the University of Ottawa Heart Institute. Sheldon Tobe reports receiving a KMH clinic unrestricted grant and in-kind support for the Zero to Five study, paid to Sunnybrook Research Institute; consulting fees from AstraZeneca; and payment for the CHEP+ education program from Amgen, Astra-Zeneca, BMS, Bayer, Boehringer Ingelheim, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer and Sanofi Genzyme. Dr. Tobe also holds a volunteer role with the American Hypertension Specialists Certification Program. No other competing interests were declared.

*   This article has been peer reviewed.

*   **Contributors:** All of the authors contributed to the conception and design of the work. Rahul Jain and Sheldon Tobe wrote the first draft and subsequent versions of the manuscript. All of the authors gave final approval of the version to be published and agreed to be accountable for all aspects of the work.

*   **Funding:** Funding for the development of the 2022 C-CHANGE guideline was provided by the Canadian Vascular Network through a Canadian Institutes of Health Research (CIHR) 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 (grant no. 06668 and 0669). Updates to the implementation tools have been made with in-kind support from the CHEP+ scientific planning committee members, as well as the Ontario College of Art and Design Health Design Unit’s graduate student program. The funders did not have a direct influence on the process, the content of the recommendations or the preparation of the manuscript.

*   **Endorsements:** Diabetes Canada; Canadian Association of Bariatric Physicians and Surgeons; Heart and Stroke Foundation of Canada; Hypertension Canada.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: [https://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/)

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