Reviewing And Excerpting From Section 4 Treatment From ACC 2023 Chronic Choronary Disease Guideline

Additional Resources

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Today, I review excerpts from Section 4 Treatment from ACC 2023 Chronic Choronary Disease Guideline.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Circulation. 2023 Aug 29;148(9):e9-e119. doi: 10.1161/CIR.0000000000001168. Epub 2023 Jul 20.

All that follows is from the above resource.

4 Treatment

4.1 General Approach to Treatment Decisions

Recommendations for General Approach to Treatment Decisions

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
1	C-LD	1. In patients with CCD, clinical follow-up at least annually is recommended to assess for symptoms,1-12 change in functional status, adherence to and adequacy of lifestyle and medical interventions,13-15 and monitoring for complications of CCD and its treatments.16-18
2b	B-NR	2. In patients with CCD, use of a validated CCD-specific patient-reported health status measure may be reasonable to assess symptoms, functional status, and QOL.19-23

Synopsis

The ultimate goals for treatment of CCD are to prolong survival and improve QOL. To do this, treatments should target a reduction in (1) cardiac death, (2) nonfatal ischemic events, (3) progression of atherosclerosis, and (4) symptoms and functional limitations of CCD while considering patient preferences, potential complications of procedures/medications, and costs to the health care system. When engaging patients in shared decision-making (Section 4.1.3), clinicians should clearly identify that some therapies may improve patient’s symptoms whereas other therapies may reduce the risk of ischemic events. To optimize treatment for each patient, several factors should be considered (Figure 4).^24,25

First, a global assessment of the risk of the patient is needed (Section 3), including both the risk of ischemic events and complications of potential treatment options. Second, obtaining a careful assessment of symptoms of CCD, functional limitations, and QOL is important. Third, SDOH (Section 4.1.4) must be considered. Fourth, the patient must be educated (Section 4.1.2) so they can actively participate in shared decision-making (Section 4.1.3). Finally, a team-based approach (Section 4.1.1) can help patients and clinicians navigate this process.

Recommendation-Specific Supportive Text

1.

Patients with CCD comprise a heterogeneous group that includes those with or without angina, a history of coronary revascularization, and previous ACS. The goals of routine clinical follow-up in these patients include: (a) to assess for new or worsened symptoms, change in functional status, or decline in QOL; (b) to assess for adherence to and adequacy of recommended lifestyle and medical interventions, including physical activity, nutrition, weight management, stress reduction, smoking cessation, immunization status, blood pressure (BP) and glycemic control, and antianginal, antithrombotic, and lipid-lowering therapies13-15; and (c) to monitor for complications of disease or adverse effects related to therapy.16,17 Although there are insufficient data on which to base a definitive recommendation regarding frequency, clinical follow-up evaluation at least annually is recommended and may be sufficient if the patient is stable on optimized GDMT and reliable enough to seek care with a change in symptoms or functional capacity. For select individuals, an annual in-person evaluation may be supplemented with telehealth visits when clinically appropriate.26 Implementation of remote, algorithmically driven-disease management programs may provide a useful adjunctive strategy to achieve GDMT optimization in eligible patients.27

2.

Revascularization1-3,12 and antianginal medications4-7 primarily reduce the symptoms of CCD. The factor most strongly associated with improvement in symptoms and QOL after revascularization is the burden of ischemic symptoms before intervention.8-12,28-30 Thus, assessment of symptoms at each clinic visit is important to identify times when additional interventions could be useful, as well as to quantify the symptomatic response to interventions. Observational studies suggest that clinicians may inaccurately estimate the burden of ischemic symptoms,19-21 which can lead to under-22 or overtreatment.21 Validated patient-reported disease-specific health status measures (eg, 7-item Seattle Angina Questionnaire31)* may help to reliably quantify the burden of CCD symptoms and reduce variation in assessment among clinicians.23 Furthermore, patient-reported disease-specific health status instruments also measure how the patient’s angina affects their QOL, which should be an important component of the treatment decision process. Although several studies showed deficiencies with clinician estimation of patient’s symptoms, no studies show an improvement in quality of care or outcomes with routine use of patient-reported measures in clinical care.

Resources For The Seattle Angina Questionnaire

• The Seattle Angina Questionnaire
• Development and Validation of a Short Version of the Seattle Angina Questionnaire
• State of the Art Review: Interpreting the Seattle Angina Questionnaire as an Outcome in Clinical Trials and in Clinical Care [PubMed Abstract] [Full Text HTML] [Full-Text PDF]. JAMA Cardiol. 2021 May 1; 6(5): 593–599. doi: 10.1001/jamacardio.2020.7478. Merrill Thomas 1, Philip G Jones 1, Suzanne V Arnold 1, John A Spertus 1.

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Resuming Excerpts From Section 4

4.1.1 Team-Based Approach

Recommendation for Team-Based Approach

Referenced studies that support the recommendation are summarized in the Online Data Supplement.

COR	LOE	Recommendation
1	A	1. In patients with CCD, a multidisciplinary team-based approach is recommended to improve health outcomes, facilitate modification of ASCVD risk factors, and improve health service utilization.∗ 1-13

Synopsis

A patient-centered, team-based approach that focuses on shared decision-making is essential to monitoring and managing patients’ CCD symptoms throughout their disease course. These recommendations apply to all aspects of clinical practice for long-term management of CCD. A team-based approach can effectively be applied to nearly all aspects of CCD management and care. Continuous communication among the care team, the patient, and any caregivers is essential to optimize outcomes and meet patient needs. Figure 5 reflects the interconnectedness of the patient and caregiver to the care team and the care team members to each other. Components of the health care team include but are not limited to: physicians; nurse practitioners; physician assistants; nurses and nursing assistants; pharmacists; dietitians; exercise physiologists; physical, occupational, and speech therapists; psychologists; and social workers.

Recommendation-Specific Supportive Text

1.

RCTs and systematic reviews with meta-analysis show that a patient-centered, multidisciplinary, team-based approach can improve patient self-efficacy, health-related QOL, and ASCVD risk factor management compared with usual care in patients with CCD who also may have hypertension, diabetes, or hyperlipidemia.1-8,11-13,15-34 Patients actively involved in their care with the medical team tend to have greater knowledge and confidence in self-management, which improves health-related QOL.1,21,32 Team-based care also facilitates behavior change and promotes weight loss, tobacco cessation, and reduces depression.8,12,16,31,33,35 A team-based approach may be more cost-effective and cost-efficient compared with usual care and reduces emergency department visits, unplanned health service utilization, cardiovascular complications in patients with diabetes, and readmission costs.6,7,9,10,20-22,27,28,31,32,34 A large cohort study comparing health care resource utilization of >1 million patients with either diabetes or ASCVD found that, overall, health care resource utilization was comparable among patients receiving care from physicians compared with advanced practice providers, although physicians work with larger patient panels.9 Communication through telehealth, patient education sessions, specialty clinics, medication therapy management, and patient decision support aids are appropriate and useful methods for providing patient care.36 Refer to Sections 4.1, 4.2, 4.3, and 7 for management.

4.1.2 Patient Education

Recommendations for Patient Education

Referenced studies that support the recommendations are summarized in Online Data Supplement.

COR	LOE	Recommendations
1	C-LD	1. Patients with CCD should receive ongoing individualized education on symptom management, lifestyle changes, and SDOH risk factors to improve knowledge and facilitate behavior change.1
1	C-LD	2. Patients with CCD should receive ongoing individualized education on medication adherence to improve knowledge and facilitate behavior change.2-4

Synopsis

Patient education is defined as “the process by which health professionals and others impart information to patients that will alter their health behaviors or improve their health status.’’^1,5 Systematic reviews of studies using educational interventions suggest they improve patient knowledge and facilitate behavior change,¹ although impact on sustained lifestyle change, cholesterol and BP levels, and morbidity and mortality rates are less clear.^5-7 A meta-analysis of secondary prevention programs suggested education and counseling after MI reduced mortality but not recurrent MI.⁶ In contrast, a review of RCTs on educational interventions among patients with various manifestations of coronary disease concluded that education had no effect on total mortality, recurrent MI, or hospitalizations.⁵ Yet, Swedish registry data suggest that the education component of CR is strongly linked to cardiovascular and total mortality.⁷ Published studies of educational interventions for patients with CCD, whether provided in person or by Internet, are heterogeneous, often incompletely described, many are short-term, and outcomes assessment varies. At this time, there are insufficient comparative data to provide clinicians and their care teams assistance when choosing among interventions, a gap that should be addressed in future research studies.

4.1.3 Shared Decision-Making

Recommendations for Shared Decision-Making

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
1	C-LD	1. Patients with CCD and their clinicians should engage in shared decision-making particularly when evidence is unclear on the optimal diagnostic or treatment strategy, or when a significant risk or benefit tradeoff exists.1-3
2b	B-R	2. For patients with CCD and angina on GDMT who are engaged in shared decision-making regarding revascularization, a validated decision aid may be considered to improve patient understanding and knowledge about treatment options.4

Synopsis

Shared decision-making is a collaborative decision-making process that includes patient education about risks, benefits, alternatives to treatment and testing options, and clinician ascertainment of patient values and goals. Shared decision-making helps to maximize patient engagement in medical decision-making, increase patient knowledge about their care, and align treatment decisions with patient preferences. Even when evidence suggests one treatment or testing modality compared with another may lead to improved cardiovascular outcomes at a population level, the optimal treatment or testing choice for an individual patient may vary based on patient values and preferences, as well as the financial implications of the choice to the patient. Decision aids can improve knowledge and reduce decisional conflict in shared decision-making, but few validated decision aids are available for patients with CCD. Clinician-patient conversations, as well as corresponding educational materials, should be tailored to the patient’s preferred language, reading level, health literacy, and visual acuity.

4.1.4 Social Determinants of Health

Recommendation for SDOH

Referenced studies that support the recommendation are summarized in the Online Data Supplement.

COR	LOE	Recommendation
1	B-R	1. In patients with CCD, routine assessment by clinicians and the care team for SDOH is recommended to inform patient-centered treatment decisions and lifestyle change recommendations.∗ 1-8

∗ Modified from the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease.⁹

Synopsis

SDOH, such as health care access, economic stability, and social context are key drivers of persistent health disparities and health inequities.^1,10-13 SDOH have profound influences on the health and well-being of patients with CCD and have become increasingly recognized in cardiovascular medicine.^2,9,10,14-18 There is an intersection of SDOH with sex, socioeconomic class, race, ethnicity, sexual orientation, and social vulnerabilities.^12,19-21 SDOH impact all stages of CCD management, including secondary prevention, treatment, access to care, and patient follow-up (Section 7.1, “Follow-Up Plan and Testing”) and self-management.¹⁴ Clinicians should ensure health equity in cardiovascular care by viewing each patient through an SDOH lens with cultural humility to formulate comprehensive care plans (Figure 6). Brief, evidence-based screening tools are available to support clinicians in identifying SDOH that may negatively affect health outcomes and health care utilization.^4,13,22-24 Routine SDOH screening in patients with CCD by clinicians or front-line staff should encompass assessment of mental health (Section 4.2.2), psychosocial stressors, health literacy, sociocultural influences (language, religious affiliation, body image), financial strain, transportation, insurance status, barriers to adherence to a heart healthy diet (food security) (Section 4.2.1, “Nutrition, Including Supplements”), neighborhood or environmental exposures (Section 4.2.11), and viable options for regular physical activity (Section 4.2.10, “Cardiac Rehabilitation”) and social support.^1,2,25 Based on identified barriers or needs, collaborative cardiovascular care teams can provide tangible and practical community-based resources and services to patients.^2,26-28 Operationalization of guidelines on addressing SDOH requires embedding health equity into clinical practice, team-based care, patient education, and shared decision-making tools (Sections 4.1.1, 4.1.2, and 4.1.3).^{13,14,17,19,29-33}

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Figure 6

Social Determinants of Health and Cardiovascular Care for Patients With CCD

• Identifies SDOH issue. ✓ Considerations for clinicians and care teams. CCD indicates chronic coronary disease, and SDOH, social determinants of health.

4.2 Guideline-Directed Management and Therapy

4.2.1 Nutrition, Including Supplements

Recommendations for Nutrition, Including Supplements

Referenced studies that support the recommendations are summarized in Online Data Supplement.

Recommendations
COR	LOE	Nutrition
1	B-R	1. In patients with CCD, a diet emphasizing vegetables, fruits, legumes, nuts, whole grains, and lean protein is recommended to reduce the risk of CVD events.∗1-4
2a	B-NR	2. In patients with CCD, reducing the percentage of calories from saturated fat (<6% of total calories) and replacing with dietary monounsaturated and polyunsaturated fat, complex carbohydrates, and dietary fiber can be beneficial to reduce the risk of CVD events.∗1-6
2a	B-NR	3. In patients with CCD, minimization of sodium (<2,300 mg/d; optimally 1,500 mg/d) and minimization of processed meats (eg, cured bacon, hot dogs) can be beneficial to reduce the risk of CVD events.∗2,3,6,7
2a	B-NR	4. In patients with CCD, limiting refined carbohydrates (eg, containing <25% whole grain by weight, including refined cold ready-to-eat breakfast cereal, white bread, white rice), and sugar-sweetened beverages (eg, soft drinks, energy drinks, fruit drinks with added sugars) can be beneficial to reduce the risk of CVD events.∗2-4,6,8
3: Harm	B-NR	5. In patients with CCD, the intake of trans fat should be avoided because trans fat is associated with increased morbidity and mortality rates.∗9,10
	Nutrition Supplements
3: No Benefit	B-NR	6. In patients with CCD, the use of nonprescription or dietary supplements, including omega-3 fatty acid, vitamins C, D, E, beta-carotene, and calcium, is not beneficial to reduce the risk of acute CVD events.11-22

∗ Modified from the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease.²³

Synopsis

Among patients with CCD, dietary behavior changes along with GDMT are important to reduce the risk of acute CVD events including ASCVD, and outcomes related to HF, stroke, and CVD-related deaths.^1,2,24 Among patients with CCD, it is well established that healthy dietary choices improve management of CVD risk factors and target pathophysiologic mechanisms contributing to acute CVD events.^25,26 Studies across diverse populations support the health benefits of a higher intake of whole grains and fiber, with lower intake of saturated fat, sodium, refined carbohydrates, and sweetened beverages^23,27,28 (Figure 7). Healthy dietary choices combined with caloric reduction will support weight loss goals and improve cardiometabolic health for overweight and obese patients.^29,30 In contrast, nonprescription nutrition or dietary supplements²⁸ have insufficient evidence to support their use to reduce the risk of acute CVD events in patients with CCD.^18,31 For this guideline, nutrition supplements is defined by the National Institutes of Health – Office of Dietary Supplements as nonprescription, dietary supplements that contain minerals (eg, calcium), herbs, amino acids, and vitamins across all dosage forms (eg, tablets, gummies).³²

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4.2.2 Mental Health Conditions

Recommendations for Mental Health Conditions

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
2a	B-R	1. In patients with CCD, targeted discussions and screening for mental health is reasonable for clinicians to assess and to refer for additional mental health evaluation and management.1-4
2a	B-R	2. In patients with CCD, treatment for mental health conditions with either pharmacologic or nonpharmacologic therapies, or both, is reasonable to improve cardiovascular outcomes.2,4-6

Synopsis

Mental health has a major role in overall cardiovascular health and well-being in patients with CCD.⁷ Mental health is defined as “a state of well-being in which an individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and is able to make a contribution to his or her community.”⁸ Mental health can have positive or negative effects on cardiovascular risk factors and outcomes.^7,9 It is estimated that 20% to 40% of patients with CCD have concomitant mental health conditions such as depression and anxiety.^10,11 Meta-analyses have shown that negative psychological states (eg, general distress) are associated with MACE in men and women with CCD.¹² Despite being a modifiable prognostic risk factor for CCD outcomes, screening for mental health disorders is seldom addressed in the clinical setting.^4,13 Potentially underpinning the bidirectional relationship between mental health and CCD is the resulting influence on health behaviors (eg, medication and CR adherence, diet, physical activity, sleep, smoking) and risk factors (eg, BP, lipids, body mass index [BMI], inflammation, thrombosis).^4,7 Pharmacologic and psychotherapeutic treatments may reduce recurrent cardiovascular events and mortality rate in patients with CCD.^5,14-17 See Section 4.1.4 for discussion of the interplay between mental health and SDOH.

Table 6Suggested Screening Tool to Assess Psychological Distress: Patient Health Questionnaire-2 Depression Screen

Over the past 2 weeks, how often have you been bothered by the following problems?	Not at all	Several days	More than half the days	Nearly every day
Little interest or pleasure in doing things	0	1	2	3
Feeling down, depressed, or hopeless	0	1	2	3
Total score of ≥3 warrants further assessment for depression.

Data derived from Kroenke et al.³¹ and Levine et al.^7,46 Reprinted with permission from Levine GN et al. Copyright 2021 American Heart Association, Inc.

Table 7Suggested Screening Questions to Assess Psychological Health

Well-being parameter	Question
Health-related optimism	How do you think things will go with your health moving forward?
Positive affect	How often do you experience pleasure or happiness in your life?
Gratitude	Do you ever feel grateful about your health? Do you ever feel grateful about other things in your life?

Data derived from Levine GN et al.^7,46 Reprinted with permission from Levine GN et al. Copyright 2021 American Heart Association, Inc.

4.2.3 Tobacco Products

Recommendations for Tobacco Products

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
1	A	1. In patients with CCD, tobacco use should be assessed at every health care visit to facilitate identification of those who may benefit from behavioral or pharmacologic interventions.∗ 1-3
1	A	2. Patients with CCD who regularly smoke tobacco should be advised to quit at every visit.∗ 4
1	A	3. In patients with CCD who regularly smoke tobacco, behavioral interventions are recommended to maximize cessation rates in combination with pharmacotherapy, including bupropion, varenicline, or combination long- and short-acting nicotine replacement therapy (NRT).∗ 5-7
2b	B-R	4. In patients with CCD who regularly smoke tobacco, varenicline may be considered versus bupropion or NRT to increase cessation rates.6
2b	B-R	5. In patients with CCD who regularly smoke tobacco, the short-term use of nicotine-containing e-cigarettes may be considered to aid smoking cessation, although the risk of sustained use and unknown long-term safety may outweigh the benefits.8-10
3: Harm	B-NR	6. Patients with CCD should avoid secondhand smoke exposure to reduce risk of cardiovascular events.∗ 11,12

∗ Modified from the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease.¹³

Synopsis

Tobacco smoke exposure, in particular cigarette smoking, is a leading cause of CVD and cardiovascular events in persons with CCD.^14-18 Cigarette smoke adversely affects endothelial function, promotes atherosclerosis, and is prothrombotic.¹⁹ Beneficial short-term effects of smoking cessation include a decrease in heart rate and BP and improved endothelial function.^20,21 Prospective cohort studies of patients with CCD show that smoking cessation is associated with a 36% reduction in death and a 32% reduction in MI.²² Pharmacotherapy and behavioral therapy in combination can increase the success of smoking cessation. Observational studies on smokeless tobacco (including snuff, snus, and chewing tobacco) and cardiovascular risk have found mixed results, but an increased risk of coronary heart disease events may be observed, albeit to a lesser degree than cigarette smoking.^23-26

Table 8Behavioral Resources for Smoking Cessation

Resource	Description
Telephone-based: Quitline English: 1-800-QUIT-NOW (1-800-784-8669) Spanish: 1-855-DÉJELO-YA (1-855-335-3569) Mandarin and Cantonese: 1-800-838-8917 Korean: 1-800-556-5564 Vietnamese: 1-800-778-8440	Counseling by telephone from a trained tobacco coach who offers support via a series of scheduled telephone calls before and after a smoker’s quit date. Patients can self-refer to the Quitline, or clinicians can refer patients, with their consent, proactively. Quitline services vary by state, can include text messaging and web coaching support, and may provide free samples of nicotine replacement therapy. State-by-state information about Quitline services is available at https://www.cdc.gov/tobacco/patient-care/quitlines-other/index.html
Web-based: American Lung Association Freedom From Smoking https://www.lung.org/quit-smoking/join-freedom-from-smoking	Created by the American Lung Association to support smoking cessation in persons who want to quit. The program also provides information about nicotine replacement therapy and pharmacotherapy. Multiple modes of support available to patients, including group clinics, a telephone-based “Lung HelpLine,” a self-help guide, and a web-based interactive customized program. Interactive program available for computer, tablet, or smartphone interface.
Web-based: National Cancer Institute English: Smokefree.gov Spanish: https://espanol.smokefree.gov/Spanish	Supported by the US Department of Health and Human Services and National Institutes of Health, created by the National Cancer Institute. Website contains information about quitting and resources for quitting and allows users to create a personalized quit plan. Specific websites are also available for women, teens, Veterans, and those >60 y of age. Programs available through the website include: SmokefreeTXT (text messaging program), QuitGuide, and quitSTART (mobile phone apps).
Web-based: Asian Smokers’ Quitline Mandarin, Cantonese, Korean, and Vietnamese Speakers https://www.asiansmokersquitline.org/	Operated by the Moores Cancer Center at the University of California, San Diego, funded by a grant from the US Centers for Disease Control and Prevention. Created to support tobacco cessation for persons who speak Mandarin, Cantonese, Korean, and Vietnamese across the United States. Some participants may be eligible for a 2-wk starter kit of nicotine patches. Telephone counseling developed to deliver a quit plan and support quitting, and printed self-help materials sent to participants.
Web-based: BecomeAnEX Available in English and Spanish https://www.becomeanex.org	Created by the Truth Initiative, a nonprofit public education in partnership with the Mayo Clinic Nicotine Dependence Center. Website with information about cessation of smoking, vaping, or use of smokeless tobacco, with resources to build an individualized quit plan. Includes support from experts and an online community, and a text message–based program for quitting vaping focused on teens and young adults, “This is Quitting.” An employer-based program, the EX Program, is also available through the Truth Initiative.

4.2.4 Alcohol and Substance Use

Recommendations for Alcohol and Substance Use

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
1	C-LD	1. Patients with CCD should be routinely asked and counseled about substance use to reduce ASCVD events.1-5
2a	B-NR	2. In patients with CCD who consume alcohol, it is reasonable to limit alcohol intake (≤1 drink/d for women, ≤2 drinks/d for men) to reduce cardiovascular and all-cause death.6-8
3: No Benefit	B-NR	3. Patients with CCD should not be advised to consume alcohol for the purpose of cardiovascular protection. 9,10

Synopsis

Various substances can have adverse effects on the cardiovascular system, including cocaine, amphetamines, opioids, alcohol, and marijuana (Table 9). These substances also have the potential for abuse and drug-drug interactions with cardiovascular therapies. Because some of these substances are illicit (eg, cocaine, heroin), studies examining the link between substances and patients with CCD are limited, observational, and with imprecise measures of exposure risk. Although observational data show a J-shaped relationship between alcohol consumption and cardiovascular risk, no RCTs support moderate alcohol consumption to reduce cardiovascular risk.^6,11 In fact, recent studies suggest that no safe level of alcohol use is acceptable and that previously observed cardioprotective effects of light-to-moderate alcohol use are likely confounded by other lifestyle and sociodemographic factors.⁸ With the recent legalization of marijuana and its derivatives in some states, its use in patients with CCD is expected to grow.¹ A scientific statement from the AHA highlights the cardiac-specific effects of cannabis, including stimulation of the sympathetic nervous system, platelet activation, endothelial dysfunction, and carbon monoxide toxicity from smoking and inhalation.¹² Observational studies of the association between marijuana and cardiovascular events are limited by selection bias with rigorous data about the long-term effect of marijuana and cardiovascular risk lacking.^12,13 The AHA released a scientific statement discussing the importance of distinguishing and managing out-of-hospital cardiac arrests from opioids and in engaging patients with opioid use disorders in secondary prevention programs.¹⁴ Because of potential cardiac toxicity, drug-drug interactions, and high risk for misuse, long-term opioid use for patients with CCD and chronic pain should be avoided. For recommendations regarding tobacco products, please see Section 4.2.3.

Table 9 Substances With Abuse Potential and Adverse Cardiovascular Effects for Patients With CCD∗

Substance	Potential Adverse Cardiovascular Effects
Alcohol	▪ J-shaped relationship between alcohol intake and cardiovascular risk in observational studies but limited by confounding.18 ▪ Heavy alcohol use and binge drinking associated with increased morbidity and mortality rates.9,10,19 ▪ May increase serum triglycerides. ▪ Potential drug-drug interactions with cardiovascular therapies.
Cocaine, methamphetamine	▪ Stimulation of the sympathetic nervous system.5,20 ▪ Platelet activation and aggregation.20 ▪ Increased myocardial oxygen demand.5 ▪ Can present with cocaine-associated chest pain. ▪ MI risk independent of route of administration.21
Opioids	▪ Possible association with risk of MI in chronic use.22 ▪ High potential for dependence and abuse with chronic use. ▪ Potential for drug-drug interactions with cardiovascular therapies.
Marijuana	▪ Stimulation of the sympathetic nervous system. ▪ Platelet activation. ▪ Endothelial dysfunction. ▪ Carbon monoxide toxicity from smoking and inhalatation.12 ▪ Route of administration may impact toxicity, with edible products associated with fewer acute cardiovascular symptoms.23

CCD indicates chronic coronary disease; and MI, myocardial infarction.

∗ List is not all inclusive.

4.2.5 Sexual Health and Activity

Recommendations for Sexual Health and Activity

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
2a	B-NR	1. In patients with CCD, it is reasonable to individualize resumption of sexual activity based on type of sexual activity, exercise capacity, and postprocedural healing.∗ 1,2
2a	B-NR	2. In patients with CCD, cardiac rehabilitation and regular exercise can be useful to reduce the risk of cardiovascular complications with sexual activity.∗ 3
3: Harm	B-NR	3. In patients with CCD, phosphodiesterase type 5 inhibitors should not be used concomitantly with nitrate medications because of risk for severe hypotension.∗ 4

∗ Modified from the 2012 AHA Scientific Statement on Sexual Activity and Cardiovascular Disease.⁵

Synopsis

Sexual health is important to QOL. Sexual activity represents moderate physical activity at around 3 to 5 metabolic equivalents.⁵ If a patient with CCD can reach this level during exercise testing without ischemia or symptoms, then the risk for ischemia during sexual activity is low, especially considering the short exposure period.² It is rare for a patient to die from cardiac disease during sexual intercourse; in this regard, men appear more at risk than women,⁶ with the absolute rate being very small. Sexual activity is associated with 1% of all MIs.³ Men and women with CCD and its risk factors have a high prevalence of sexual dysfunction.⁷ Recent MI and coronary artery bypass surgery may additionally compromise sexual function⁵; in this regard, sexual counselling may be helpful, and resuming sexual activity does not appear to be associated with an increased risk of death. Of particular relevance to patients with CCD is the need to avoid the combined use of nitrates with phosphodiesterase type 5 inhibitors.⁴

Recommendation-Specific Supportive Text

1.	Recommendations after PCI and CABG may depend on whether femoral or radial access was performed, and whether surgery was performed in a sternal-sparing manner.5,8 The patient should be well compensated, euvolemic, and without significant angina. Patients with CCD who are functionally well compensated or patients with no or mild angina, given the low risk of MI or sudden death, should be considered safe for sexual activity. Sexual activity represents an exercise level of approximately 3 to 5 metabolic equivalents, compared with a typical exercise treadmill test that involves approximately 4 metabolic equivalents. The risk of MI or sudden death resulting from sexual activity is very low. 3 Patients with CCD who want to engage in sexual activity should undergo a medical evaluation, similar to other forms of exercise in the presence of CCD.5 Because sexual activity is associated with increased metabolic requirements, patients with unstable or decompensated CCD should refrain from sexual activity.5
2.	In addition to a recommendation for CR incorporating sexual counseling, in men with CCD, conservative measures such as sexual rehabilitation, consisting of 12 weeks of sexual rehabilitation with physical exercise training, pelvic floor exercise and psychoeducation, was associated with better sexual function by the International Index of Erectile Function.9,10
3.	Phosphodiesterase type 5 inhibitors should not be used concomitantly with nitrate medications, often used to treat CCD, because of the potential for severe hypotension.4 Sildenafil and vardenafil have half-lives of ∼4 hours. Tadalafil is long-acting and has a half-life of 17.5 hours. Patients on sildenafil or vardenafil should avoid taking nitroglycerine for ≥24 hours (≥48 hours for tadalafil).5 In patients on long-acting nitrate therapy who want to use a phosphodiesterase type 5 inhibitor, decision on the use of phosphodiesterase type 5 inhibitor should be guided by the need for continued nitrate therapy versus other alternative options available to the treating clinician.

4.2.6 Lipid Management

Recommendations for Lipid Management

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
1	A	1. In patients with CCD, high-intensity statin therapy is recommended with the aim of achieving a ≥50% reduction in LDL-C levels to reduce the risk of MACE.∗ 1-3
1	A	2. In patients in whom high-intensity statin therapy is contraindicated or not tolerated, moderate-intensity statin therapy is recommended with the aim of achieving a 30% to 49% reduction in LDL-C levels to reduce the risk of MACE.∗ 2,4-8
1	A	3. In patients with CCD, adherence to changes in lifestyle and effects of lipid-lowering medication should be assessed by measurement of fasting lipids in 4 to 12 weeks after statin initiation or dose adjustment and then every 3 to 12 months thereafter based on need to assess response or adherence to therapy.∗ 2,9-11
Cost Value Statement: High Value	B-NR	4. In patients with CCD, the use of generic formulations of maximally tolerated statin therapy is projected to be cost saving.12,13
2a	B-R	5. In patients with CCD who are judged to be at very high risk (Table 10) and on maximally tolerated statin therapy with an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), ezetimibe can be beneficial to further reduce the risk of MACE.∗14-19
Cost Value Statement: High Value	B-NR	6. In patients with CCD, addition of generic ezetimibe to maximally tolerated statin therapy in appropriately selected patients is projected to be of high economic value at US prices.12,20,21
2a	A	7. In patients with CCD who are judged to be at very high risk (Table 10) and who have an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), or a non–high-density lipoprotein cholesterol (HDL-C) level ≥100 mg/dL (≥2.6 mmol/L), on maximally tolerated statin and ezetimibe, a PCSK9 monoclonal antibody can be beneficial to further reduce the risk of MACE.∗22-29
Cost Value Statement: Uncertain	B-NR	8. In patients with CCD who are very high risk, the use of PCSK9 monoclonal antibodies is projected to be of uncertain economic value at US prices12,20,21,30,31
2b	B-R	9. In patients with CCD on maximally tolerated statin therapy with an LDL-C level <100 mg/dL (<2.6 mmol/L) and a persistent fasting triglyceride level of 150 to 499 mg/dL (1.7–5.6 mmol/L) after addressing secondary causes, icosapent ethyl may be considered to further reduce the risk of MACE and cardiovascular death.32
2b	B-R	10. In patients with CCD who are not at very high risk and on maximally tolerated statin therapy with an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), it may be reasonable to add ezetimibe to further reduce the risk of MACE.∗ 14,15,18,19
2b	B-R	11. In patients with CCD on maximally tolerated statin therapy who have an LDL-C level ≥70 mg/dL (≥1.8 mmol/L), and in whom ezetimibe and PCSK9 monoclonal antibody are deemed insufficient or not tolerated, it may be reasonable to add bempedoic acid33,34 or inclisiran35 (in place of PCSK9 monoclonal antibody) to further reduce LDL-C levels.
3: No Benefit	B-R	12. In patients with CCD receiving statin therapy, adding niacin,36,37 or fenofibrate38 or dietary supplements containing omega-3 fatty acids, are not beneficial in reducing cardiovascular risk.39-41

∗ Modified from the 2018 AHA/ACC/Multisociety Guideline on the Management of Blood Cholesterol.⁴²

Synopsis

LDL-C is a primary cause of atherosclerotic disease and target of lipid management.³⁸ RCTs established the efficacy and safety of high-intensity statin therapy as the preferred initial approach to reduce LDL-C levels by ≥50% and reduce cardiovascular morbidity and mortality rates (Figure 8).^1-3 Despite maximally tolerated statin therapy, residual cardiovascular risk persists, especially among patients with CCD and additional high-risk clinical factors (Table 10).^14-17 Several nonstatins^36-38 did not provide benefit when added to background statin therapy; however, ezetimibe, PCSK9 monoclonal antibodies, and icosapent ethyl further reduce cardiovascular risk when added to background statin therapy.^15,22,23,32 Bempedoic acid and inclisiran have only recently become available and, although they effectively reduce LDL-C levels,^34,35 RCTs are ongoing to determine their effect on MACE. Clinicians should prioritize use of ezetimibe and PCSK9 monoclonal antibodies when additional LDL-C lowering is necessary in patients on maximally tolerated statin therapy unless not tolerated or effective in achieving desired LDL-C levels. Regardless of the lipid-lowering regimen, lipid monitoring is essential to assess individual response to lipid-lowering therapy and monitor adherence and persistence with therapy over time.^9-11

fig1 JACC folder when server ready

Figure 8

Lipid Management in Patients With CCD

Colors correspond to Class of Recommendation in Table 3. Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions (Table 10). ∗Only when ezetimibe and PCSK9 mAb are deemed insufficient or not tolerated should bempedoic acid or inclisiran (in place of PCSK9 mAb) be considered to further reduce LDL-C levels. The effect of bempedoic acid and inclisiran on MACE is being evaluated. LDL-C indicates low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; PCSK9 mAb, PCSK9 monoclonal antibody; RCT, randomized controlled trial; and TG, triglycerides.

Table 10 Very High-Risk of Future ASCVD Events

Definition of Very High-Risk∗

History of multiple major ASCVD events

OR

One major ASCVD event AND ≥2 high-risk conditions

Major ASCVD Events

Recent ACS (within the past 12 mo)

History of MI (other than recent ACS events listed above)

History of ischemic stroke

Symptomatic peripheral artery disease (history of claudication with ABI <0.85, or previous revascularization or amputation)51

High-Risk Conditions

Age ≥65 y

Familial hypercholesterolemia†

History of previous coronary artery bypass graft surgery or percutaneous coronary intervention outside of the major ASCVD event(s)

Diabetes

Hypertension

Chronic kidney disease (eGFR, 15–59 mL/min/1.73 m2)15,29

Current tobacco smoking

Persistently elevated LDL-C ≥100 mg/dL despite maximally tolerated statin therapy and ezetimibe

History of congestive heart failure

ABI indicates ankle brachial index; ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; and MI, myocardial infarction.

Modified with permission from Grundy SM, et al.⁴² Copyright 2019 American Heart Association, Inc., and American College of Cardiology Foundation.

∗ Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions.

† Management of patients with familial hypercholesterolemia often requires combination lipid lowering therapy and referral to a lipid specialist, and possibly lipoprotein apheresis.^58,59

Recommendation-Specific Supportive Text

1.	The CTT (Cholesterol Treatment Trialists) meta-analysis of 5 RCTs showed that LDL-C lowering with high-intensity statins compared with moderate-intensity statins reduces major vascular events by 15% (Table 11).2 This benefit occurred irrespective of age, even among patients >75 years of age with established ASCVD.2,3 Greater absolute reductions in LDL-C were associated with a greater proportional reduction in MACE. The greatest absolute benefit from statin therapy is observed in those with the highest baseline LDL-C levels and at similar risk of events. Furthermore, percent reduction in LDL-C appears to provide additional prognostic value overachieved LDL-C levels.43 The expected percent reduction in LDL-C levels with high-intensity statin therapy is ≥50% and should be used to assess clinical efficacy. However, baseline LDL-C levels in patients before statin initiation are not always available in clinical practice. The threshold of LDL-C ≥70 mg/dL is then useful to determine whether to intensify lipid management.
2.	Although high-intensity statin therapy is preferred, high-intensity statin therapy may not be tolerated by some patients or may be contraindicated because of clinically significant drug-drug interactions.44 Statin intolerance is defined as adverse effects associated with statin therapy that improve or resolve with dose modification or discontinuation of statin therapy; and requires a trial of at least 2 statins with one at the lowest approved daily dose.45 Statin intolerance may also be complete or partial (tolerating less than the recommended statin intensity). Clinicians should also consider the possibility of a “nocebo effect”—patient expectation of harm resulting in perceived adverse effects.46 Multiple RCTs showed that moderate-intensity statin therapy also reduces cardiovascular events and death among patients with established ASCVD, including those >75 years of age; therefore, a moderate-intensity statin should be used in patients unable to tolerate a high-intensity statin.2,4-8 Additional strategies may also be used to identify a tolerable statin regimen (eg, low-intensity statin, alternative daily dosing) to reduce LDL-C but it is unclear if these strategies also reduce the risk of ASCVD events.47
3.	The goal for LDL-C lowering is defined as percentage responses in LDL-C relative to baseline levels. Although reductions in LDL-C are expected with moderate- and high-intensity statins (Table 11), individual response can vary substantially.11 The maximum percentage change in LDL-C occurs within 4 to 12 weeks after initiation of or change in lipid-lowering therapy. The Friedewald equation is known to underestimate LDL-C in the setting of elevated TG levels, thus other approaches to LDL-C measurement (eg, Martin/Hopkins method) may be desirable.48,49 Obtaining lipid profile measurements every 3 to 12 months is associated with increased adherence to therapy and identification of patients requiring further intensification of treatment.9,10 See Sections 4.4.3 and 5 of the 2018 AHA/ACC multisociety cholesterol guideline50 for additional information regarding efficacy and safety monitoring.
4.	The economic value of a lipid-lowering therapy depends on the absolute benefit (in terms of the number of cardiovascular events averted or quality-adjusted life years [QALY] gained) that patients derive from receiving the treatment relative to the comparator as well as the cost of the therapy being evaluated.13 Because of the very low annual cost of generic formulations of statins in the United States, the use of maximally tolerated statin therapy in patients with CCD is projected to be cost-saving (ie, the lifetime savings from averted cardiovascular events more than offset the lifetime cost of statin therapy and resulting adverse effects).12 Note that this value statement should not be extrapolated to higher-cost branded formulations of statins.
5.	In IMPROVE-IT (Improved Reduction of Outcomes; Vytorin Efficacy International Trial), the addition of ezetimibe to moderate-intensity statin therapy among patients with ACS resulted in a significant ASCVD risk reduction (7% relative risk reduction; 2% absolute risk reduction) at a median follow-up of 6 years.15 An analysis using the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2 P) found the addition of ezetimibe was associated with significantly greater risk reduction (19% relative risk reduction; 6.3% absolute risk reduction) among patients with ≥3 high-risk features, with more modest benefit among those with 2 high-risk features and no benefit among those with 0 or 1 additional features.14 Ezetimibe was allowed at study entry in both PCSK9 monoclonal antibody trials,23,24 but only 3% and 5%, respectively, were on ezetimibe. No RCT has evaluated whether an ezetimibe-first strategy is preferred before adding a PCSK9 monoclonal antibody; however, clinicians should generally add ezetimibe first, then a PCSK9 monoclonal antibody, if necessary, to achieve desired LDL-C levels, given the generic availability of ezetimibe, its once-daily oral administration, and proven long-term safety and tolerability. This is supported by 2 well-designed simulation studies showing that a high proportion of patients will achieve an LDL-C level of <70 mg/dL with the addition of ezetimibe to high-intensity statin therapy.18,19
6.	Generic ezetimibe is an inexpensive drug, with net price of <$10 for a 1-month supply. To the extent that LDL-C lowering with ezetimibe translates to fewer lifetime MACE, the use of generic ezetimibe is likely to be improve health outcomes at modest increase in cost, especially in very high-risk patients, resulting in high value (<$50,000 per QALY gained).12,20,21 However, the cost-effectiveness of adding generic ezetimibe to maximally tolerated statin therapy is sensitive to the assumption regarding the effect of ezetimibe on cardiovascular and all-cause death.
7.	Very high risk ASCVD is defined in Table 10. The efficacy of alirocumab and evolocumab was shown in 2 RCTs.22,23 The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition Subjects with Elevated Risk) trial evaluated evolocumab among those with established ASCVD with an LDL-C level of ≥70 mg/dL or non–HDL-C level of ≥100 mg/dL on maximal statin with or without ezetimibe. Cardiovascular events were significantly reduced by 15% with evolocumab, with greater benefit observed among those with additional high-risk clinical factors. No increased risk of neurocognitive adverse effects was observed, even among those achieving the very low levels of LDL-C.29 The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) trial evaluated alirocumab use in patients with an ACS event 1 to 12 months earlier on maximal statin with or without ezetimibe. Cardiovascular events were significantly reduced by 15% with alirocumab, especially in those with additional high-risk clinical factors.25-27 The absolute risk reduction was relatively modest (1.5% and 0.6%, respectively) in both trials, given the ∼60% reduction in LDL-C levels. However, analyses from both FOURIER and ODYSSEY Outcomes trials subsequently showed that among several groups of patients noted in the very high-risk ASCVD category (Table 10), the absolute risk of future ASCVD events was significantly higher; therefore, the absolute risk reduction from the use of a PCSK9 monoclonal antibody was also much higher than the overall absolute risk reductions seen in the original trials.23,26,28,51,52 Although generally well tolerated, injection site reactions can occur, and long-term safety data are limited. Maximal LDL-C-lowering therapy should include maximally tolerated statin plus ezetimibe; however, ezetimibe may be insufficient when a ≥25% reduction in the LDL-C level is desired. Clinicians bypassing the addition of ezetimibe before adding a PCSK9 monoclonal antibody should recognize this may not be cost effective (Figure 8).
8.	The US cost of PCSK9 monoclonal antibodies has declined by 60% since their initial market entry (from approximately $14,000 per year to $5,850 per year), which, all things being equal, has improved the cost-effectiveness of these drugs.12,20,21 At this price point, the cost-effectiveness of the agents in very high risk patients with CCD is uncertain, with some studies projecting low economic value12,20 and others suggesting intermediate to high economic value.30,31 This value statement should not be extrapolated to patients with CCD who are at low to moderate risk of adverse cardiovascular events, in whom PCSK9 inhibitor monoclonal antibodies are of low economic value. The cost-effectiveness of a therapy is a function of the incremental cost of the therapy relative to the comparator, its effectiveness relative to the comparator, as well as baseline risk of cardiovascular events in the target population. Patients who have higher baseline risk are likely to derive a larger absolute health benefit from an effective drug. It follows that CVD prevention is more cost-effective in a population at higher risk of CVD events. Thus, PCSK9 inhibitors may be intermediate value in patients at higher-than-average risk of recurrent events, such as those with a recent ACS, symptomatic peripheral artery disease, or familial hypercholesteremia (FH).12,20,21 The cost-effectiveness of PCSK9 monoclonal antibody is also likely improved in patients who are unable to tolerate statins because of severe statin-associated side effects.12
9.	REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized patients with established ASCVD or diabetes plus additional risk factors, triglyceride levels between 150 mg/dL and 499 mg/dL, and an LDL-C level of <100 mg/dL on background statin therapy, to either 4 g/day of icosapent ethyl (purified EPA only) or mineral oil placebo. Icosapent ethyl significantly reduced the relative risk of MACE by 25% and cardiovascular death by 20%.32 The benefit appeared driven by the increase in EPA levels and not the modest 17% reduction in triglyceride levels. RESPECT-EPA (Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy-Statin and Eicosapentaenoic Acid) was another secondary prevention trial that showed a borderline significant reduction in MACE with icosapent ethyl 1800 mg/day (10.9% versus 14.9%; P=0.055) in 2506 participants enrolled in Japan on background statin therapy. Limitations of this trial were the lack of placebo control, and it was underpowered. Contrarily, the STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) trial found no benefit with a 4 g/day carboxylic acid formulation of omega-3 fatty acids (EPA and DHA) compared with a corn oil placebo, and no association with harm or benefit in those at the highest achieved tertiles for EPA and DHA levels. Incident AF was more common with both icosapent ethyl and the carboxylic acid formulation of omega-3 fatty acids and has been observed in other studies of omega-3 fatty acid formulations. Several factors could explain the discrepant outcomes observed in these trials; however, the use of a mineral oil placebo in REDUCE-IT is of concern given its adverse effects on lipid and inflammatory biomarkers, suggesting mineral oil may not be an inert placebo.53 For patients with LDL-C levels between 70 mg/dL and <100 mg/dL, it is unclear whether further LDL-C lowering or adding icosapent ethyl is more effective. Patient preference and shared decision-making are recommended, and secondary causes of elevated triglyceride levels (eg, medications, diabetes, lifestyle) should be addressed before considering icosapent ethyl. Dietary supplements containing omega-3 fatty acids are not acceptable substitutes for icosapent ethyl.
10.	In patients not at very high risk, there may be instances where high-intensity statin therapy is insufficient to achieve desired LDL-C levels or not tolerated. Although moderate-intensity statin therapy effectively reduces cardiovascular risk, it is inferior to high-intensity statin therapy.2 Additional LDL-C lowering may also be necessary in patients on moderate-intensity statin therapy with LDL-C levels ≥70 mg/dL. Adding ezetimibe to moderate-intensity statin therapy may compensate for the reduced LDL-C lowering observed with moderate-intensity statin therapy alone. Although the net benefit of ezetimibe may be less robust among patients not at very high risk, it is preferred before a PCSK9 monoclonal antibody for reasons provided in Recommendation 5.
11.	Bempedoic acid is a first-in class therapy adenosine triphosphate-citrate lyase54 inhibitor that reduces LDL-C levels by 15% to 25% depending on the type and dose of background statin therapy and is associated with fewer muscle-related adverse effects.33,34 It is also available in a combination product with ezetimibe that reduces LDL-C levels by ∼35%. Although it can be combined with statins, bempedoic acid should be avoided when using doses of simvastatin >20 mg daily or pravastatin 40 mg daily because of an ∼2-fold increase in serum levels of both statins. Elevation in uric acid levels may occur with bempedoic acid use, and rare cases of tendon rupture have been reported. Inclisiran is a first-in-class small interfering RNA directed to break down PCSK9 mRNA, resulting in reduced synthesis of PCSK9.35 Inclisiran reduces LDL-C levels by approximately 50% and is administered as a single subcutaneous dose, with a second dose at 3 months, then every 6 months. Inclisiran administration must be performed by a health care professional, which may limit accessibility. It is generally well tolerated, but injection site reactions can occur. The effect of bempedoic acid and inclisiran on MACE is currently under investigation; therefore, nonstatin therapies with proven efficacy (ie, ezetimibe, PCSK9 monoclonal antibody) should be prioritized over these 2 therapies. Preliminary modeling studies project that the use of bempedoic acid or inclisiran in patients unable to tolerate statin therapy because of severe statin-associated side effects is of intermediate value ($50,000–$150,000 per QALY gained), as is the use of inclisiran in patients with CCD and heterozygous FH.55 However, the cost-effectiveness of these novel therapies is sensitive to assumptions regarding the effect of each drug on cardiovascular and all-cause death and should be updated when long-term outcomes data become available.
12.	Dietary supplements containing omega-3 fatty acids (ie, fish oil) are widely used for presumed cardioprotective benefits. However, low-dose omega-3 fatty acid supplementation does not reduce MACE in patients with CCD.39-41 The only omega-3 fatty acid formulation that can be recommended in patients with CCD is icosapent ethyl (EPA only) as described in Recommendation 9. The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health) trial found no benefit with the addition of extended-release niacin to background statin therapy.36 Another niacin trial in secondary prevention, HPS2-THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events), also found no benefit with a combination product of niacin and laropiprant, a prostaglandin receptor antagonist; however, this product is no longer available.37 ACCORD-LIPID (Action to Control Cardiovascular Risk in Diabetes-Lipid Trial)56 found no benefit with the addition of fenofibrate to background statin therapy. Although this trial was conducted in patients with type 2 diabetes, more than half of the trial participants had established CVD at baseline, and no benefit was observed in this subgroup of patients. A selective PPARα modulator, pemafibrate, was investigated in the PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Diabetic Patients) trial in high-risk patients with diabetes, but this trial was stopped early for futility.57 Fenofibrate should only be considered for severe hypertriglyceridemia (triglycerides, ≥500 mg/dL) to reduce the risk of acute pancreatitis.

Table 11High-, Moderate-, and Low-Intensity Statin Therapy∗

	High Intensity	Moderate Intensity	Low Intensity
LDL-C Lowering†	≥50%	30%-49%	<30%
Statins	Atorvastatin (40 mg‡), 80 mg Rosuvastatin 20 mg (40 mg)	Atorvastatin 10 mg (20 mg) Rosuvastatin (5 mg) 10 mg Simvastatin 20-40 mg§	Simvastatin 10 mg
		Pravastatin 40 mg (80 mg) Lovastatin 40 mg (80 mg) Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 1-4 mg	Pravastatin 10-20 mg Lovastatin 20 mg Fluvastatin 20-40 mg

Percent LDL-C reductions with the primary statin medications used in clinical practice (atorvastatin, rosuvastatin, simvastatin) were estimated using the median reduction in LDL-C from the VOYAGER database.¹¹ Reductions in LDL-C for other statin medications (fluvastatin, lovastatin, pitavastatin, pravastatin) were identified according to FDA-approved product labeling in adults with hyperlipidemia, primary hypercholesterolemia, and mixed dyslipidemia.⁶⁰

Boldface type indicates specific statins and doses that were evaluated in RCTs and the Cholesterol Treatment Trialists’ 2010 meta-analysis.^2,3 These RCTs demonstrated a reduction in major cardiovascular events.

FDA indicates US Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; RCT, randomized controlled trial; VOYAGER, an indiVidual patient data meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin; and XL, extended release.

Reprinted with permission from Grundy SM, et al.⁴² Copyright 2019 American Heart Association, Inc., and American College of Cardiology Foundation.

∗ Percent reductions are estimates from data across large populations. Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice.¹¹

† LDL-C lowering that should occur with the dosage listed below each intensity.

‡ Evidence from 1 RCT only: down titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study.⁶¹

§ Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy, including rhabdomyolysis.

Table 12 Nonpharmacologic Strategies for Blood Pressure Management∗

Nonpharmacologic Intervention		Dose	Approximate Impact on SBP
			Hypertension	Normotension	Reference
Weight loss	Weight/body fat	Best goal is ideal body weight but aim for at least a 1-kg reduction in body weight for most adults who are overweight. Expect about 1 mm Hg for every 1-kg reduction in body weight.	−5 mm Hg	−2/3 mm Hg	5
Healthy diet	DASH dietary pattern	Consume a diet rich in fruits, vegetables, whole grains, and low-fat dairy products, with reduced content of saturated and total fat.	−11 mm Hg	−3 mm Hg	2,3
Reduced intake of dietary sodium	Dietary sodium	Optimal goal is <1,500 mg/d but aim for at least a 1,000-mg/d reduction in most adults.	−5/6 mm Hg	−2/3 mm Hg	29,30
Enhanced intake of dietary potassium	Dietary potassium	Aim for 3,500–5,000 mg/d, preferably by consumption of a diet rich in potassium.	−4/5 mm Hg	−2 mm Hg	35
Physical activity	Aerobic	▪ 90–150 min/wk ▪ 65%–75% heart rate reserve	−5/8 mm Hg	−2/4 mm Hg	4,8
	Dynamic resistance	▪ 90–150 min/wk ▪ 50%–80% of 1 repetition maximum ▪ 6 exercises, 3 sets/exercise, 10 repetitions/set	−4 mm Hg	−2 mm Hg	4
	Isometric resistance	▪ 4×2 min (hand grip), 1 min rest between exercises, 30%–40% maximum voluntary contraction, 3 sessions/wk ▪ 8–10 wk	−5 mm Hg	−4 mm Hg	36,37
Moderation in alcohol intake	Alcohol consumption	In individuals who drink alcohol, limit alcohol† to: ▪ Men: ≤2 drinks daily ▪ Women: ≤1 drink daily	−4 mm Hg	−3 mm Hg	6

DASH indicates Dietary Approaches to Stop Hypertension; and SBP, systolic blood pressure.

Resources: Your Guide to Lowering Your Blood Pressure With DASH—How Do I Make the DASH?³⁸ Available at: https://www.nhlbi.nih.gov/files/docs/public/heart/new_dash.pdf.

Modified with permission from Whelton PK, et al.¹⁹ Copyright 2018 American Heart Association, Inc., and American College of Cardiology Foundation.

∗Type, dose, and expected impact on BP in adults with a normal BP and with hypertension.

† In the United States, 1 “standard” drink contains roughly 14 g of pure alcohol, which is typically found in 12 oz of regular beer (usually about 5% alcohol), 5 oz of wine (usually about 12% alcohol), and 1.5 oz of distilled spirits (usually about 40% alcohol).

4.2.7 Blood Pressure Management

Recommendations for Blood Pressure Management

Referenced studies that support the recommendations are summarized in the Online Data Supplement.

COR	LOE	Recommendations
1	A	1. In adults with CCD, nonpharmacologic strategies are recommended as first-line therapy to lower BP in those with elevated BP (120-129/<80 mm Hg) (see Table 12).∗1-9
1	B-R	2. In adults with CCD who have hypertension, a BP target of <130/<80 mm Hg is recommended to reduce CVD events and all-cause death.∗ 10-14
1	B-R	3. In adults with CCD and hypertension (systolic BP ≥130 and/or diastolic BP ≥80 mm Hg), in addition to nonpharmacological strategies, GDMT angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB), or beta blockers15-17 are recommended as first-line therapy for compelling indications (eg, recent MI or angina), with additional antihypertensive medications (eg, dihydropyridine calcium channel blockers [CCB], long-acting thiazide diuretics, and/or mineralocorticoid receptor antagonists) added as needed to optimize BP control.∗ 13,18

∗ Modified from the 2017 ACC/AHA Multisociety Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.¹⁹

Synopsis

Hypertension is a well-established risk factor for CVD²⁰ and is a highly prevalent comorbid condition among individuals with CCD, affecting >60% of such individuals.²¹ Individuals with CCD who also have hypertension are at increased risk of death and morbidity compared with individuals with CCD who are normotensive.²² Treatment of hypertension with lifestyle^1-6,22 and medication therapies^{13,16,17,23-28} helps control hypertension and reduce subsequent risk of MACE. The recommendations apply to individuals with CCD who have hypertension. See Section 4.2.1 for additional recommendations regarding nutritional therapies and Sections 4.2.10 to 4.2.11 for additional recommendations about physical activity and CR. For additional information, see the 2017 ACC/AHA multisociety guideline for the prevention, detection, evaluation, and management of high blood pressure in adults.¹⁹

Recommendation-Specific Supportive Text

1.	Lifestyle-related factors influence BP levels, and lifestyle modifications are effective strategies to help lower elevated BP. These factors include weight loss,1,5 a heart-healthy diet that is rich in fruits and vegetables,2,3 reduced dietary sodium,29,30 physical activity,4,8 and reduction or elimination of alcohol intake.6
2.	Among patients with increased cardiovascular risk, reduction of systolic BP to <130 mm Hg has been shown to reduce CVD complications by 25% and all-cause death by 27%.13 Optimal diastolic BP for clinical outcomes appears to be in the range of 70 to 80 mm Hg.10,14
3.	In the HOPE (Heart Outcomes Prevention Evaluation) trial, ramipril therapy in patients with CVD or at high risk for CVD reduced the risk of MI, stroke, or CVD by 22% compared with placebo.16 In patients with CAD and hypertension who were randomized into the INVEST (International Verapamil SR/Trandolapril Study) trial, CCB and ACE inhibitors and beta-blocker/thiazide diuretic therapy had similar cardiovascular morbidity and death outcomes.31 In the EUROPA (Exclusive Endocrine Therapy or Partial Breast Irradiation for Women ≥70 Years Early Stage Breast Cancer) study involving patients with CCD, ACE inhibitor therapy produced a 20% reduction in risk of CVD death, MI, or cardiac arrest compared with placebo.15 Beta blockers are particularly effective in patients with CCD, especially those with recent MI and those with ongoing angina, given their ability to reduce angina, improve angina-free exercise tolerance, reduce exertion-related myocardial ischemia, and reduce risk of CVD events.17,23,27,32,33 Because of the significant benefits from beta blockers and ACE inhibitors and ARB agents in patients with CCD, these medications are recommended as a first-line therapy in the treatment of hypertension in such individuals. GDMT beta blockers for CCD and for lowering BP include carvedilol, metoprolol tartrate, metoprolol succinate, nadolol, bisoprolol, propranolol, and timolol.19 Outcomes with atenolol appear to be inferior compared with other antihypertensive drugs in the treatment of hypertension.34 When beta blockers, ACE inhibitors, and ARB therapies do not sufficiently control BP, additional GDMT BP-lowering therapies can be added, including thiazide diuretics, CCB, and mineralocorticoid receptor antagonists.19