Approach

General approach

The treatment goals of patients with chronic coronary disease (CCD) are to:

  • Improve quality of life by eliminating or reducing symptoms and restoring level of activity

  • Improve outcomes by reducing complications including myocardial infarction (MI) and death.

A multidisciplinary team approach that involves the patient in shared decision-making is recommended.

Education and lifestyle modification

Patients with CCD should have an individualized education plan to optimize care and promote wellness. It is important to educate patients on the importance of medication adherence for managing symptoms and retarding disease progression.[26]​ The patient should be made aware of medication management strategies that reduce cardiovascular risk in a manner that respects his or her level of understanding, reading comprehension, and culture. The patient and provider together should review all therapeutic options including a discussion of appropriate levels of exercise, with encouragement to maintain recommended levels of daily physical activity, self-monitoring skills, and information on how to recognize worsening cardiovascular symptoms and how to take appropriate action.

Cardiac rehabilitation

  • Cardiac rehabilitation is a multidisciplinary approach that combines assessment, education, assistance with lifestyle modification, psychosocial support, and supervised exercise. Guidelines recommend cardiac rehabilitation after MI and revascularization as well as for patients with stable angina. Benefits after infarction or revascularization include reduced mortality, reduced rehospitalization and quality of life. Patients with angina experience primarily symptomatic benefit.[23][26]​​[137] [ Cochrane Clinical Answers logo ] ​​ [ Cochrane Clinical Answers logo ] ​ There is developing evidence to support home-based alternatives to facility-based programs.[138][139][140]

Physical activity

  • Exercise recommendations for patients with CCD are similar to those in the general population: at least 150 minutes of moderate-intensity aerobic activity, such as brisk walking, per week or at least 75 minutes of higher-intensity aerobic activity. In addition, strength (resistance) training is recommended at least 2 days a week.[141]​ Formal exercise may be supplemented by an increase in lifestyle activities (e.g., walking breaks at work, using the stairs, gardening, household work) to improve cardiorespiratory fitness.[26]​ Although patients with CCD should generally be encouraged regarding the benefits of exercise, high-risk patients may benefit from a basic evaluation to rule out unstable angina or other contraindications. Selective use of stress testing may be considered for sedentary patients with CCD prior to initiation of vigorous exercise.[23]

Diet

  • A Mediterranean-type diet, with a higher intake of vegetables, fruits, legumes, nuts, whole grains, and lean protein (e.g., fish) is recommended.[23][26]​​[142]​ Intake of saturated fats should be reduced and replaced with unsaturated fats, complex carbohydrates, and fiber. Intake of processed meat, refined carbohydrates, and sweetened drinks should be minimized or avoided. Sodium intake should be minimized and trans fat should be avoided.[23][26]​​[143]

  • When consumed, alcohol should be limited.[23][26]​​

  • There is insufficient evidence to recommend use of dietary supplements, including omega-3 fatty acids.[26][144][145]

Weight management

  • Guidelines recommend routine assessment of body mass index (BMI) with or without waist circumference in patients with CCD. For those with overweight or obesity, counseling on weight loss, with goals including reducing body weight with diet and physical activity, is advised.[23][26]​​​​​ Guidelines further advise consideration of pharmacologic therapy and bariatric surgery in selected patients.[26]

  • Although weight loss interventions improve cardiovascular risk factors (including weight, blood pressure, lipids, insulin resistance) there is limited evidence of improved cardiovascular outcomes in weight loss trials.[48]​ Given the imperfections of BMI as a risk marker, the limited efficacy of even multicomponent lifestyle interventions in promoting sustained weight loss, and concern for weight stigma as a barrier to care, providers might also focus on physical activity and cardiorespiratory fitness rather than weight per se as a treatment goal.

  • See Obesity in adults.

Smoking cessation

  • Smoking cessation and avoidance of exposure to environmental tobacco smoke at work and home should be encouraged for all patients with coronary disease. Follow-up, referral to special programs, and pharmacotherapy are recommended, as is a stepwise strategy for smoking cessation.[26]​ See Smoking cessation.​​

  • Observational studies show that smoking cessation is associated with a greater than one third reduction in coronary disease mortality.[146] The benefits appear within a few years. After 10 to 15 years of abstinence, risk is similar to or minimally higher than that of people who have never smoked.[147]​ One Cochrane review found that in people with coronary disease, stopping smoking at diagnosis is associated with a reduction of approximately one‐third in the risk of recurrent cardiovascular disease.[148]

Stress and depression recognition and management

  • Depression is common in patients with CCD, particularly after acute infarction. It is associated with worse health behaviors and possibly worse cardiovascular outcomes.[149] Evidence on the cardiac effects of depression treatment is limited, but it is reasonable to screen patients and treat as indicated.[23][26]​​​[150]

Vaccine recommendations

  • Influenza infection is associated with adverse cardiovascular events such acute MI, and there is strong evidence that vaccination of patients with CCD can reduce those outcomes.[151][152][153][154]​ The effect of other vaccines (e.g., COVID-19, pneumococcus, RSV) on cardiac outcomes is less well defined, but patients with CCD may be at increased risk of serious complications from these infections.[23][26]​​[155][156]

Guideline-directed management to improve outcomes

Guideline-directed therapy is recommended where indicated to reduce risk of cardiovascular events. Treatments with the strongest evidence and widest applicability are:

  • Low-dose aspirin

  • High-intensity statins

Select patients may also benefit from:

  • Beta-blockers

  • Renin-angiotensin-aldosterone antagonists

  • Additional or alternative antiplatelet or anticoagulant medications

  • Additional lipid management

  • Blood pressure control

  • Diabetes management.

Low-dose aspirin

  • Antiplatelet therapy protects against platelet activation and acute thrombosis, and thereby reduces the risk of MI and sudden death.

  • Low-dose aspirin should be prescribed indefinitely in most patients with coronary disease, although European guidelines make a less strong recommendation for patients with CCD without prior infarction or revascularization.[23][26]​​​ Aspirin reduces the relative risk of nonfatal MI by 20%.[157]​ Aspirin for secondary prevention is frequently underused.[158]

  • Low doses of aspirin are as effective as higher doses and have a lower risk of gastrointestinal, major, and life-threatening bleeding.[159][160]​ In a large pragmatic trial outcomes were similar but 42% of patients assigned to high-dose aspirin switched to low-dose.[161]

Additional/alternative antiplatelet and anticoagulant medications

  • Clopidogrel is at least as effective as aspirin in reducing vascular events.[162] However, its use as monotherapy is generally reserved for patients with contraindications to aspirin.[23][26]​​​

  • Dual antiplatelet therapy (DAPT) - the use of aspirin combined with P2Y12-receptor inhibitors such as clopidogrel - increases the risk of bleeding and is not universally beneficial for patients with CCD.[26][163][164][165]​ European, but not US, guidelines endorse consideration of long-term DAPT for patients with particularly high risk of ischemic events but not high risk of bleeding.[23]

  • After an episode of acute coronary syndrome (ACS), US and European guidelines recommend DAPT for 1 year. This recommendation applies whether the ACS is treated medically or percutaneously, or surgically. Shorter or longer durations of DAPT may be reasonable in patients at high or low bleeding risk, respectively. Outside of the acute preprocedural period, clopidogrel is recommended in all scenarios; alternative P2Y12 inhibitors may be appropriate in selected cases.[165][166]

  • After percutaneous coronary intervention (PCI), DAPT can prevent the rare but morbid complication of in-stent thrombosis as well as reduce the risk of MI unrelated to the stent. US guidelines recommend 6 months of DAPT following placement of contemporary drug-eluting stents and 1 month of DAPT following placement of a bare metal stent. European guidelines recommend 6 months of DAPT regardless of stent type. Both guidelines acknowledge that shorter or longer duration of DAPT may be reasonable depending on bleeding risk.[165][166]

  • Scoring systems (such as Precise DAPT or the American College of Cardiology DAPT risk calculator) can assist clinicians in weighing the antithrombotic benefit and bleeding risk of extended DAPT.

  • DAPT poses markedly increased bleeding risk in patients taking vitamin K antagonists or direct oral anticoagulants (DOAC). For patients taking anticoagulation for indications such as atrial fibrillation (AF), mechanical heart valves, or venous thromboembolism, triple therapy is generally avoided or used for as short a period as possible.[26][165][166]​​

  • European guidelines recommend routine use of proton-pump inhibitors (PPI) with DAPT to reduce the risk of gastrointestinal hemorrhage.[166] US guidelines recommend selective use.[26][165]​​​ Despite concerns, trials have not shown that PPIs reduce the efficacy of clopidogrel.[167]

  • For selected patients with CCD at high-risk of ischemic events but low-risk of bleeding who do not have a separate indication for anticoagulation, the addition of low-dose rivaroxaban to aspirin monotherapy can reduce a combined cardiovascular outcome. The benefit is primarily reduced stroke and peripheral arterial disease rather than MI and comes at the cost of increased bleeding.[26][168]

Statins and other lipid-lowering medications

  • High-intensity statins are the mainstay of lipid pharmacotherapy and appropriate for all patients with CCD (unless clearly contraindicated), regardless of baseline low-density lipoprotein (LDL). High-intensity statin therapy is indicated for most patients.​[26][63]​​​[99]​​

  • Meta-analysis of placebo-controlled and higher-versus-lower dose trials show that statin therapy reduces coronary death and nonfatal MIs regardless of baseline LDL cholesterol. In placebo-controlled trials, lower-potency statins reduce the relative risk of these major coronary events by 27%. Although there have not been large placebo-controlled studies of high-potency statins in the CCD population, the degree of benefit appears proportional to the intensity of statin therapy, with a relative reduction of major coronary events of approximately 25% per 40 mg/dL reduction in LDL-cholesterol achieved.[169] On the basis of these data, some authorities suggest approximating the benefit of statin therapy as a relative risk reduction of 1% for each 1% reduction in LDL achieved, more for higher baseline LDL and less for lower baseline LDL.[44]

  • Statins, particularly high-dose statins, have been less well studied in patients aged over 75 years but meta-analysis suggests similar efficacy for patients with existing vascular disease irrespective of age.[170]

  • Statins are usually well tolerated. Serious adverse events including liver injury, myonecrosis, and rhabdomyolysis are rare.[171]

  • When patients develop possible adverse effects, such as myalgias, every effort should be undertaken to ascertain whether these are actually related to the medication. Alternative statins, lower doses, or alternative dosing schedules may be tried.

  • Despite few treat-to-target trials of lipid management, US and European guidelines recommend achieving a reduction of at least 50% from baseline LDL.​[44][99][172]​​​ In addition, particularly for patients with CCD at very high-risk, guidelines recommend an absolute LDL value below 70 mg/dL (1.81 mmol/L), or in some cases even lower.[44][99]​​ If these reductions are not achieved with lifestyle modification and statin therapy, additional medications can be indicated.

  • The evidence supporting statin therapy in CCD far exceeds that of other lipid-lowering medications. However, for patients unable to take statins, or who have a less than expected reduction in LDL despite adherence at the highest tolerated dose, ezetimibe monotherapy or combination therapy with ezetimibe and a statin may be considered.[26]​​[44]​​​ For patients at very high risk with persisting elevations in LDL, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor may be added (although cost may remain a barrier). Newer nonstatin therapies are approved (e.g., bempedoic acid, inclisiran); however, until there is evidence of improved cardiac outcomes use cases are limited.[26][173]​ See Emerging treatments.

  • Medications to lower triglycerides have not shown clear benefit in CCD outcomes. A single trial showed benefit from icosapent ethyl, although there are questions about harm from the placebo mineral oil driving that result.[174]​ US guidelines suggest a possible role for icosapent ethyl after modification of lifestyle factors and management of LDL. However, they recommend against use of other omega-3-fatty-acid preparations, niacin, or fenofibrate for the purpose of reducing cardiovascular risk.[26]

  • The decision to add nonstatin therapies should be shared between patient and clinician following a discussion on the risks and benefits, and taking into account patient preferences and costs. Lifestyle modifications should be optimized, in addition to reviewing adherence to statins.

Beta-blocker therapy

  • Beta-blockers decrease heart rate and myocardial contractility and, in turn, reduce myocardial oxygen demand and anginal symptoms. In selected patients with CCD, beta-blockers may also have a role in improving cardiac outcomes. The best evidence is in patients with CCD and reduced ejection fraction (EF), for whom metoprolol, carvedilol, and bisoprolol particularly reduce cardiac events including cardiac death.[175]​​[176][177][178]

  • Older trials showed improved outcomes in patients with recent MI. However, the benefits are less clear for contemporary studies in which acute reperfusion and statin use are more common.[179]​ Studies of long-term use of beta-blockers after infarction are observational and do not show consistent benefit in patients with normal EF.[180][181][182][183]

  • The US and European guidelines recommend beta-blocker therapy for patients with systolic dysfunction.[23][26]​​​ The US guidelines do not recommend long-term beta-blocker therapy to improve outcomes in patients with CCD in the absence of MI in the past year, left ventricular EF ≤50%, or another primary indication for beta-blocker therapy (e.g., angina, arrhythmia, uncontrolled hypertension).[26]

Renin-angiotensin-aldosterone antagonist therapy

  • ACE inhibitors result in a reduction in angiotensin II with an increase in bradykinin. These changes in the physiological balance between angiotensin II and bradykinin could contribute to the reductions in LV and vascular hypertrophy, atherosclerosis progression, plaque rupture, and thrombosis through favorable changes in cardiac hemodynamics and improved myocardial oxygen supply and demand. Clinical studies have demonstrated significant reductions in the incidence of acute MI, unstable angina, and need for coronary revascularization in patients after MI with LV dysfunction, independent of etiology.[184][185][186]​ Similar benefits have been seen in patients without LV dysfunction who have atherosclerosis, vascular disease, diabetes, and additional risk factors for coronary disease.[187][188][189]

  • The US and European guidelines recommend ACE inhibitors (or angiotensin-II receptor antagonists) primarily for patients with CCD who also have hypertension, systolic dysfunction, diabetes mellitus, or chronic kidney disease. Use can also be considered for those with CCD who have other vascular disease or are at very high risk of cardiovascular events.[23][26]​​​

Blood pressure control

  • Lifestyle modification is recommended for patients with CCD and elevated blood pressure (120 to 129/<80mmHg). For patients with CCD and hypertension (≥130 mmHg systolic and/or ≥80 mmHg diastolic), guidelines recommend pharmacologic and nonpharmacologic treatment to achieve a target below 130/80 mmHg.[26]​ The European guidelines suggest a relaxed systolic target of 130 to 140 for patients over 65 years old.[23]

  • Lifestyle modifications may include increased physical activity, Dietary Approaches to Stop Hypertension (DASH) or mediterranean diet pattern, reduced dietary sodium and alcohol, and weight reduction.[190][191]

  • In choosing antihypertensive medications, guidelines give priority to beta-blockers and ACE inhibitors/angiotensin-II receptor antagonists in select patients with CCD and hypertension.[23][26]​​​ For patients with MI in the past year, beta-blockers may reduce coronary events more than other antihypertensives.[192]​ In placebo-controlled trials, ACE inhibitors improve outcomes for patients with CCD generally and after MI but it is less clear that these agents offer better outcomes than other antihypertensives.​​[185][187][188]​ For patients with stable angina, both beta-blockers and calcium-channel blockers can have symptomatic benefit.

Management of diabetes

  • For patients with type 2 diabetes, two classes of medication have shown significant cardiovascular benefits beyond their effects on glycemia. These include sodium-glucose transporter-2 (SGLT2) inhibitors (e.g., empagliflozin, dapagliflozin, canagliflozin), and glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, dulaglutide).[40][193][194][195][196][197]​​ For patients with CCD and type 2 diabetes, use of either one of these medications is recommended independent of A1c.[26][198]​​ Use of both an SGLT2 inhibitor and a GLP-1 receptor agonist may be considered when needed for additional glycemic control but the additional cardiovascular benefits of the combination have not been defined. There is no established role for use of SGLT2 inhibitors or GLP-1 receptor agonists to improve cardiac outcomes in patients without diabetes or heart failure.[26]​ One study has shown improved cardiac outcomes with use of a GLP-1 receptor agonist in patients with obesity.[199]

  • Of older, less costly medications, there is weak evidence of cardiovascular benefit with metformin compared with sulfonylureas.[200]

  • Patients with CCD and diabetes mellitus are at high-risk of morbidity and mortality from cardiovascular events. In type 1 diabetes, glycemic control reduces the risk of macrovascular complications including angina, MI, and need for revascularization.[201]

  • In type 2 diabetes, the effects of glycemic control on macrovascular complications are less clear.[40]​ Observational studies show an association between hyperglycemia and increased risk of ischemic heart disease.[202]​ Randomized trials of more intensive glycemic control over 3 to 6 years have not shown consistent reductions in MI nor cardiac death. Meta-analyses suggest a reduction in the former but not the latter.[203][204][205][206][207][208] Longer term follow-up may be required.[209]

  • ACE inhibitors (or angiotensin-II receptor antagonists) are recommended in the US and European guidelines for patients with CCD and diabetes mellitus to reduce risk of cardiovascular events.[23][26]

Antianginal pharmacotherapy to reduce symptoms

  • Sublingual nitroglycerin (delivered by either a tablet or spray formulation) is the therapy of choice to terminate acute episodes of angina or for prophylaxis before activities known to induce anginal symptoms. Onset of action is within minutes. Failure to resolve anginal symptoms with a reduction in physical activity and a trial of sublingual nitroglycerin should prompt emergency evaluation for an ACS (unstable angina or MI).[23][26]​​​

  • For those with recurrent angina, beta-blockers, calcium-channel blockers, and long-acting nitrates have each been shown to reduce anginal events. As there are no head-to-head trials, selection among these classes may be guided by adverse effects and/or baseline hemodynamics, and the presence of systolic dysfunction.[23][26]​​[210]​ The three classes are often used in combination, although beta-blockers should not be combined with nondihydropyridine calcium-channel blockers (diltiazem, verapamil).

  • A key component of therapy with long-acting nitrates is ensuring an adequate nitrate-free period every day to avoid tolerance and loss of effect. Phosphodiesterase-5 inhibitors for erectile dysfunction should be avoided in patients using nitrates as the combination may precipitate an unsafe drop in blood pressure.[23][26]​​​

  • Patients with vasospastic (Prinzmetal variant) angina may note greater reduction of symptoms with use of calcium-channel blockers or nitrates due to their effect on coronary vasospasm.[211]

  • Second-line antianginal therapies, such as ranolazine, may be added for angina that persists despite use of combinations of primary therapies.[23][26]​​​ US guidelines warn against the use of ivabradine in patients with normal left ventricular function.[26]

Coronary revascularization

Revascularization, either by coronary artery bypass graft (CABG) surgery or by PCI, may be indicated to improve either the quality or quantity of life: to improve CCD symptoms refractory to medical therapy or to improve survival.

The US, European, and UK guidelines all recommend revascularization for patients with limiting symptoms despite maximal medical therapy.[26]​​[210][212][213]​ The guidelines also recommend revascularization in carefully selected cases to improve survival or other cardiac outcomes but disagree about exactly which patients qualify and the roles for CABG and PCI. There is consensus in favor of revascularization for patients with significant disease of the left main coronary artery but varying recommendations regarding patients with other anatomy, reduced EF, and high ischemic burden.[26]​​[210][212][213]​ Some European guidelines suggest the possibility of a less restrictive approach to revascularization but do not offer specific recommendations.[23]

The US and European guidelines emphasize the role of fractional flow reserve (FFR) in revascularization decisions.[23][26]​​[214]​ There is consensus that complex cases should be evaluated by a "heart team" including interventional cardiology and cardiothoracic surgery.[26]​​[210][212][213]

Revascularization for refractory symptoms:

  • Revascularization is indicated in patients with unacceptable symptoms despite maximal medical therapy. Symptoms may be classic angina or anginal equivalents such as dyspnea on exertion. Randomized trials have shown CABG and PCI improve anginal symptoms over medical therapy.[215][216][217]

  • Of note, the only blinded trial comparing PCI to a placebo procedure did not show benefit of PCI in relieving angina or enhancing exercise capacity.[218] The trial involved very aggressive medical management in both groups and was limited by small sample size and brief follow-up; however, it raises questions about the extent to which the apparent symptomatic benefits of PCI are due to the placebo effect.

Revascularization for survival benefit:

  • While the benefits of revascularization in the setting of ACS are clear, for patients with CCD large trials have not shown reductions in cardiovascular mortality or MI when revascularization is added to medical therapy. The classic COURAGE trial and the contemporary ISCHEMIA trial showed no benefit from revascularization on mortality or MI.[219][220][221]​ Notably, patients with obstruction of the left main coronary artery were excluded from both large trials. Meta-analyses come to different conclusions and questions remain about the definition and clinical significance of periprocedural infarcts in the ISCHEMIA trial.[217][222]

  • Trials focused solely on the mortality benefits of CABG in CCD are more dated but showed benefit in certain subgroups of patients with coronary disease.[215][223][224][225]​​ The evolution of both surgical techniques (e.g., arterial grafts, off-pump CABG) and the comparison medical therapies (e.g., statins, beta-blockers) potentially limits the relevance of these older trials to contemporary practice. PCI has not been shown to improve mortality but smaller studies and meta-analyses have suggested possible benefit from FFR-guided PCI in other cardiac outcomes.[24][226][227][228]

Considerations for management of additional specific comorbidities

Chronic kidney disease (CKD):

  • ACE inhibitors (or angiotensin-II receptor antagonists) are recommended in the US and European guidelines for patients with CCD and CKD to reduce risk of cardiovascular events.[23][26]

  • Some drugs should be used with caution in patients with renal impairment and a dose adjustment may be required. Some drugs may also be contraindicated in patients with renal impairment. Check your local drug information source. In evaluating patients for revascularization by PCI, renal risks should be considered and minimized.

  • Consult with a nephrology specialist should be considered. See Chronic kidney disease.

Heart failure (HF):

  • Patients with CCD and HF with reduced EF or HF with preserved EF should receive treatment as per current HF guidelines.[229][230]

  • In selected patients with CAD and HF with left ventricular EF ≤35% and suitable coronary anatomy, surgical revascularization in addition to GDMT for HF may improve symptoms, cardiovascular hospitalizations, and long-term all-cause mortality.[26][229][230]

  • See Heart failure with reduced ejection fraction, and Heart failure with preserved ejection fraction.

Atrial fibrillation:

  • In patients with CCD and AF, long-term anticoagulant therapy is recommended for reduction of ischemic stroke and other ischemic events.[23]​ Oral anticoagulant monotherapy (preferably with a DOAC) without antiplatelet is recommended for many patients with stable CCD.[23][26] For select patients at higher risk (either chronically or temporarily following an event or procedure) combination of a DOAC and single antiplatelet agent may be appropriate.​

  • Use of triple therapy (a DOAC plus DAPT) confers a very high bleeding risk but may be indicated for up to 1 month after PCI, followed by a single antiplatelet agent plus a DOAC for 6-12 months.[26]

  • See Established atrial fibrillation.

Peripheral artery disease (PAD):

  • The same risk factors that predispose to coronary disease increase the risk of noncoronary atherosclerotic diseases such as PAD and stroke. Measures taken to treat CCD may also reduce these adverse outcomes.

  • PAD is an important comorbidity; it is a similar disease process to coronary artery disease in a different vascular bed. Management of PAD involves exercise programs and pharmacotherapy for claudication. Management of CCD is not generally altered in the presence of PAD.

  • See Peripheral arterial disease.

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