Guidelines Summary
Lipid level management
The American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) now recommend LDL goals of < 55 mg/dL, < 70 mg/dL, < 100 mg/dL, and < 130 mg/dL for individuals at extreme, very high, high/moderate, and low risk for cardiovascular events, respectively, as outlined below. [50]
Extreme-risk patients: Goals: LDL < 55 mg/dL, non-HDL < 80 mg/dL, apolipoprotein B (apoB) < 70 mg/dL
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Progressive atherosclerotic cardiovascular disease (ASCVD), including unstable angina, in patients after achieving an LDL-C < 70 mg/dL
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Established clinical cardiovascular disease in patients with diabetes, chronic kidney disease (CKD) stages 3/4, or heterozygous familial hypercholesterolemia (HeFH)
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History of premature ASCVD (< 55 yr of age in men, < 65 in women)
Very-high-risk patients: Goals: LDL < 70 mg/dL, non-HDL < 80 mg/dL, apoB < 80 mg/dL
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Established or recent hospitalization for acute coronary syndrome (ACS); coronary, carotid, or peripheral vascular disease; 10-y risk >20%
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Diabetes or CKD stages 3/4 with one or more risk factors
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HeFH
High-risk patients: Goals: LDL < 100 mg/dL, non-HDL < 130 mg/dL, apoB < 90 mg/dL
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Two or more risk factors and 10-year risk 10-20%
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Diabetes or CKD stages 3/4 with no other risk factors
Moderate-risk patients: Goals: Same goals as high risk
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Two or more risk factors and 10-y risk < 10%
Low-risk patients: Goals: LDL < 130 mg/dL, non-HDL < 160 mg/dL, apoB not relevant
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0 risk factors
In 2002, the committee of the National Cholesterol Education Program made the following modifications to the Adult Treatment Panel III (ATP III) guidelines. [1]
In high-risk patients, a serum low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL is the goal.
In very high-risk patients, an LDL cholesterol level goal of less than 70 mg/dL is a therapeutic option. Patients in the category of very high risk are those with established coronary artery disease (CAD) with one of the following: multiple major risk factors (especially diabetes), severe and poorly controlled risk factors (especially continued cigarette smoking), multiple risk factors of metabolic syndrome (especially high triglyceride levels [≥200 mg/dL] plus non-HDL cholesterol level [≥130 mg/dL] with low high-density lipoprotein (HDL) cholesterol level [< 40 mg/dL]), and patients with ACS.
For moderately high-risk persons (2+ risk factors), the recommended LDL cholesterol level is less than 130 mg/dL, but an LDL cholesterol level of 100 mg/dL is a therapeutic option.
However, the 2013 American College of Cardiology and American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk abandoned the traditional LDL- and non-HDL–cholesterol targets. Physicians are no longer asked to treat patients with cardiovascular disease to below 100 mg/dL or the optional goal of below 70 mg/dL. Instead, the guidelines identify four groups of primary- and secondary-prevention patients in whom physicians should focus their efforts to reduce cardiovascular-disease events. Depending on the type of patient, physicians should choose the appropriate "intensity" of statin therapy to achieve relative reductions in LDL cholesterol. [51]
The clinical guidelines advise that for those with atherosclerotic cardiovascular disease, high-intensity statin therapy should be used to achieve at least a 50% reduction in LDL cholesterol unless otherwise contraindicated or when statin-associated adverse events are present. In these cases, clinicians should use a moderate-intensity statin. Similarly, for those with LDL-cholesterol levels above 190 mg/dL, a high-intensity statin should be used with the goal of achieving at least a 50% reduction in LDL-cholesterol levels. [51]
The American Association of Clinical Endocrinologists (AACE) and National Lipid Association (NLA) have declined to endorse the ACC/AHA guidelines. In particular, the AACE disagrees with the removal of the LDL targets and the idea that statin therapy alone is sufficient for all at-risk patients, noting that many who have multiple risk factors, including diabetes and established heart disease, will need additional therapies. [52, 53]
Medical Management
2012 joint guidelines from the American College of Cardiology Foundation (ACCF), AHA, American Association for Thoracic Surgery (AATS), Preventive Cardiovascular Nurses Association (PCNA), Society for Cardiovascular Angiography and Interventions (SCAI), and Society of Thoracic Surgeons (STS) offer the following recommendations for medical management of stable ischemic heart disease [54]
Class I
Individualize patient education plans to optimize care and promote wellness that includes the following:
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Review of all therapeutic options (Level of evidence: B)
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Explanation of medication management and cardiovascular risk reduction strategies in a manner that respects the patient's level of understanding, reading comprehension, and ethnicity (Level of evidence: B)
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Education on the importance of medication adherence for managing symptoms and retarding disease progression (Level of evidence C)
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Encouragement to maintain recommended levels of daily physical activity (Level of evidence: C)
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Self-monitoring skills and information on how to recognize worsening cardiovascular symptoms and how to take appropriate action (Level of evidence: C)
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Education about the lifestyle factors that could influence prognosis, such as weight control, lipid management; blood pressure control; smoking cessation and avoidance of exposure to secondhand smoke; and lifestyle changes for patients with diabetes mellitus to supplement diabetes treatment goals and education (Level of evidence: C)
Treatment with aspirin 75-162 mg daily should be continued indefinitely in the absence of contraindications in patients with stable ischemic heart disease (SIHD). (Level of evidence: A) However, treatment with clopidogrel is reasonable when aspirin is contraindicated. (Level of evidence: B)
Angiotensin converting enzyme (ACE) inhibitors should be prescribed in all patients who also have hypertension, diabetes mellitus, left ventricular ejection fraction (LVEF) of 40% or less, or chronic kidney disease, unless contraindicated. (Level of evidence: A)
Angiotensin receptor blockers (ARBs) are recommended for patients who have indications for, but are intolerant of, ACE inhibitors. (Level of evidence: A)
Beta blockers should be prescribed as initial therapy for relief of symptoms. (Level of evidence: B) However, calcium channel blockers or long-acting nitrates should be prescribed for relief of symptoms when beta blockers are contraindicated or cause unacceptable side effects. (Level of evidence: B)
Calcium channel blockers or long-acting nitrates, in combination with beta blockers, should be prescribed for relief of symptoms when initial treatment with beta blockers is unsuccessful. (Level of evidence: B)
Administer sublingual nitroglycerin or nitroglycerin spray for immediate relief of angina. (Level of evidence: B)
Class IIa
It is reasonable to educate patients about 1) adherence to a diet that is low in saturated fat, cholesterol, and trans fat; high in fresh fruits, whole grains, and vegetables; and reduced in sodium intake, with cultural and ethnic preferences incorporated (Level of evidence: B); and 2) common symptoms of stress and depression to minimize stress-related angina symptoms. (Level of evidence: C)
Class III
Dipyridamole is not recommended as antiplatelet therapy. (Level of evidence: B)
Estrogen therapy is not recommended in postmenopausal women to reduce cardiovascular risk or improve clinical outcomes. (Level of evidence: A)
Vitamin C, vitamin E, and beta-carotene supplementation are not recommended to reduce cardiovascular risk or improve clinical outcomes. (Level of evidence: A)
Treatment of elevated homocysteine with folate or vitamins B6 and B12 is not recommended to reduce cardiovascular risk or improve clinical outcomes. (Level of evidence: A)
Treatment with garlic, coenzyme Q10, selenium, or chromium is not recommended to reduce cardiovascular risk or improve clinical outcomes. (Level of evidence:C)
Acupuncture should not be used for the purpose of improving symptoms or reducing cardiovascular risk (Level of evidence: C)
In a 2014 focused update, the ACC/AHA/AATS/PCNA/SCAI/STS modified its recommendations regarding the potential benefit of chelation therapy for reducing cardiovascular events from not beneficial (Class III, level of evidence: C) to uncertain benefit (Class IIb, level of evidence: B). [55]
The 2013 European Society of Cardiology (ESC) includes the following recommendations. [56]
Class I
For optimal medical treatment, use at least one drug for angina/ischemia relief plus drugs for event prevention. (Level of evidence: C)
For angina/ischemia relief: use short-acting nitrates (Level of evidence: B); first-line treatment is with beta-blockers and/or calcium channel blockers to control heart rate and symptoms. (Level of evidence: A)
For event prevention: Use low-dose aspirin daily (Level of evidence: A); clopidogrel is indicated as an alternative in case of aspirin intolerance (Level of evidence: B). Statins are indicated for all patients with stable coronory artery disease. (Level of evidence: A). Use ACE inhibitors (or ARBs) if other conditions are present (eg, heart failure, hypertension, or diabetes). (Level of evidence: A)
Class IIa
For angina/ischemia relief (second-line treatment): Add long-acting nitrates, ivabradine, nicorandil, or ranolazine, according to the patient's heart rate, blood pressure, and tolerance (Level of evidence: C); in asymptomatic patients with large areas of ischemia (>10%) consider beta-blockers. (Level of evidence: B)
Revascularization Therapy
The 2012 ACC/AHA/AATS/PCNA/SCAI/STS guideline recommendations for surgical management include the following. [54]
Class I
Coronary artery bypass graft (CABG) is recommended to improve survival for patients with significant (≥50% diameter stenosis) left main coronary artery stenosis. (Level of evidence: B)
Class IIa
To improve survival, percutaneous coronary intervention (PCI) is reasonable as an alternative to CABG in selected stable patients with significant (≥50% diameter stenosis) unprotected left main CAD with anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome.(Level of evidence: B)
Class III
PCI should not be performed in stable patients with significant (≥50% diameter stenosis) unprotected left main CAD who have unfavorable anatomy for PCI and who are good candidates for CABG. (Level of evidence: B)
In joint 2014 guidelines for myocardial revascularization, the ESC and the European Association for Cardio-Thoracic Surgery (EACTS) indications (all Class I) for revascularization in patients with stable angina are below. [57]
For prognosis:
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Left main disease with stenosis of over 50% (Level of evidence: A)
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Any proximal left anterior descending (LAD) artery stenosis above 50% (Level of evidence: A)
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Two-vessel or three-vessel disease with stenosis above 50% with impaired LV function (LVEF < 40%) (Level of evidence: A)
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Large area of ischemia (>10% LV) (Level of evidence: B)
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Single remaining patent coronary artery with stenosis of over 50% (Level of evidence: C)
For symptom relief: Any coronary stenosis greater than 50% in the presence of limiting angina unresponsive to medical therapy (Level of evidence: A)
Dual Antiplatelet Therapy
In 2016, the ACC/AHA released updated guidelines on duration of dual antiplatelet therapy (DAPT) in patients with CAD. In this focused update, the term and acronym DAPT is used to specifically to refer to combination antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). Key recommendations for SIHD treated with PCI or CABG include those below. [58]
Class I
In patients with SIHD treated with DAPT after bare metal stent (BMS) implantation, use P2Y12 inhibitor therapy with clopidogrel for at least 1 month. (Level of evidence: A)
In patients with SIHD treated with DAPT after drug-eluting stent (DES) implantation, use P2Y12 inhibitor therapy with clopidogrel for at least 6 months. (Level of evidence: B-R)
The recommended daily dose of aspirin is 81 mg (range, 75 mg to 100 mg). (Level of evidence: B-NR)
Class IIb
It may be reasonable to continute DAPT with clopidogrel for longer than 1 month for patients with BMS or longer than 6 months for patients treated with DES if DAPT has been tolerated without a bleeding complication and the patient is not at high bleeding risk. (Level of evidence: A)
It may be reasonable to discontinue P2Y12 inhibitor therapy after 3 months in patients treated with DAPT after DES implantation who develop a high risk of bleeding or develop significant overt bleeding. (Level of evidence: C-LD)
It may be reasonable to treat with DAPT (with clopidogrel initiated early postoperatively) for 12 months after CABG to improve vein graft patency. (Level of evidence: B-NR)
Class III
In patients with SIHD without prior history of acute ACS, coronary stent implantation, or recent (within 12 months) CABG, treatment with DAPT is not beneficial. (Level of evidence: B-NR)
In 2017, the ESC updated their guidelines on DAPT, as outlined below. [59]
The latest advice in this controversial area advocates a personalized-medicine approach based on ischemic vs bleeding risks, where each treatment and its duration is individualized as much as possible.
DAPT (aspirin plus a P2Y12 inhibitor) reduces the risk of stent thrombosis and/or spontaneous MI in patients following PCI (percutaneous coronary intervention) or an ACS. The risk of bleeding in patients on DAPT is proportionally related to its duration. The benefits of prolonged DAPT, especially on mortality, depend on prior cardiovascular history (such as prior ACS/MI vs stable CAD).
For ACS patients, the default DAPT duration should be 12 months, irrespective of the revascularization strategy (medical therapy, PCI, or CABG surgery). Six months of DAPT should be considered in patients at high bleeding risk (PRECISE-DAPT score ≥25). Therapy longer than 12 months may be considered in ACS patients who have tolerated DAPT without a bleeding complication.
The need for a short DAPT regimen should no longer justify the use of bare-metal stents instead of newer-generation drug-eluting stents. DAPT duration should be guided by an assessment of the individual patient's ischemic vs bleeding risks and not by the stent type.
Irrespective of the type of metallic stent implanted, the duration of DAPT in stable CAD patients treated with PCI should be 1 to 6 months depending on the bleeding risk. A longer DAPT duration may be considered in patients whose ischemic risk is greater than the risk of bleeding.
There are insufficient data to recommend DAPT in stable CAD patients treated with CABG.
The addition of DAPT to oral anticoagulation therapy increases the risk of bleeding complications by twofold to threefold. The indication for oral anticoagulation should be reassessed and treatment continued only if there is a compelling indication such as atrial fibrillation, a mechanical heart valve, or recent history of recurrent deep venous thrombosis or pulmonary embolism. The duration of triple therapy (DAPT plus oral anticoagulation) should be limited to 6 months or omitted after hospital discharge, depending on the ischemic and bleeding risks.
Clopidogrel is recommended as the default P2Y12 inhibitor in patients with stable CAD treated with PCI, patients with an indication for oral anticoagulation, and ACS patients in whom ticagrelor or prasugrel are contraindicated. Ticagrelor or prasugrel is recommended for ACS patients unless there are drug-specific contraindications.
The decision on when to initiate a P2Y12 inhibitor depends on both the specific drug and the specific disease (stable CAD vs ACS).
CABG and anticoagulation
In 2018, the STS, Society of Cardiovascular Anesthesiologists (SCA), and American Society of ExtraCorporeal Technology (AmSECT) released their guidelines regarding anticoagulation during CABG, as summarized below. [60]
A functional whole blood test of anticoagulation, in the form of a clotting time, should be measured and demonstrate adequate anticoagulation before initiation of, and at regular intervals during, cardiopulmonary bypass (CPB).
Discontinuation of protamine and implementation of resuscitative measures, including reinstitution of CPB with adequate anticoagulation, may be lifesaving for patients at high risk for anaphylactic response to protamine who have pulmonary hypertension and circulatory collapse.
Heparin dosing calculations may differ so long as the result achieves the desired target level of anticoagulation.
It's reasonable to maintain an activated clotting time (ACT) above 480 seconds during CPB. However, ACT is a "gross and imperfect" test, and the testing platform affects the target value of ACT.
Heparin reversal should be carefully calculated with low doses of protamine, so long as heparin rebound is controlled for.
Bivalirudin is a reasonable option for patients in need of urgent surgery requiring CPB with a diagnosis of heparin-induced thrombocytopenia (HIT).
In patients with significant renal dysfunction who are seropositive for HIT and require urgent CPB-assisted surgery, use of plasmapheresis, argatroban, or heparin with antiplatelet agents, such as tirofiban and ilioprost, may be considered, understanding that there are increased risks of bleeding with these interventions.
For patients given bivalirudin who have excessive bleeding after CPB, a combination of modified ultrafiltration, hemodialysis, and the administration of recombinant factor VIIa with blood product replacement may be considered to improve hemostasis.
