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CLINICAL STATEMENTS AND GUIDELINES

August 29, 2023 Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168

Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline

improved anginal outcomes.7,8 In the CARISA (Combination Assessment of Ranolazine in Stable Angina) trial, 823 patients with CCD were randomized to placebo or 1 of 2 doses of ranolazine.7 After 12 weeks of therapy, ranolazine improved exercise capacity and more effectively relieved angina compared with placebo. In the ERICA (Efficacy of Ranolazine in Chronic Angina) trial, 565 patients with CCD and persistent symptoms despite a maximally tolerated dose of amlodipine were randomized to ranolazine or placebo.8 After 6 weeks, patients randomized to ranolazine had significantly fewer anginal episodes and less nitroglycerin consumption. 4.	 Short-acting nitrates help to relieve acute episodes

of angina.9 One can decrease symptoms by administering a short-acting nitrate prior to activity that typically triggers symptoms. In randomized studies, nitroglycerin spray in comparison with a sublingual formulation is more effective and efficient at relieving angina, but with less headache.10

5 The role of ivabradine in patients with CCD has

not been studied as extensively as other antianginal therapies. One study comparing ivabradine with atenolol and another comparing it with amlodipine in a double-blind, randomized manner both found similar improvements in exercise time and angina relief with ivabradine.18,19 Another study found that the addition of ivabradine to atenolol in patients with CCD resulted in improved exercise capacity compared with placebo.18 However, a more recent study randomized 19 102 patients with CCD, no evidence of HF, and a resting heart rate of at least 70 beats per minute to ivabradine or placebo in addition to GDMT, including standard anti-anginal treatment.11 At approximately 28-month follow-up, the rate of the primary endpoint of cardiovascular death or MI was similar between both groups. In patients with activity-limiting angina, although ivabradine led to improvement in angina class in 24% compared with 18.8% receiving placebo (P=0.01), the primary endpoint of death or MI was significantly higher in the patients randomized to ivabradine (7.6% versus 6.5%; P=0.02), suggesting possible harm when ivabradine is used in this setting.

4.3.7 Management of Refractory Angina

Recommendation for Management of Refractory Angina Referenced studies that support the recommendation are summarized in the Online Data Supplement. COR LOE Recommendation

2b B-R 1 In patients with CCD, refractory angina, and no

other treatment options, enhanced external counterpulsation may be considered for relief of symptoms.*1

*Modified from the 2012 ACC/AHA Multisociety Guideline for the Diagnosis and Management of Patients With SIHD.2 Synopsis

Refractory angina represents a small but important segment of the CCD population.3 Patients are identified by 3 major features: (1) anginal chest pain (or equivalent symptoms) that is uncontrolled despite intensive medical therapy; (2) objective evidence the anginal symptoms have an ischemic cause; and (3) no further options for coronary revascularization.4 Typically, symptoms produce major lifestyle limitations, functional status limitations, and disabilities. Some definitions also specify Canadian Cardiovascular Society Class III/IV symptoms. Some sources include patients with microvascular angina in this category. No AHA/ACC class 1 recommendations are possible given the limited evidence currently available in this area. Enhanced external counterpulsation has the weak support of a single randomized trial reported in 2005, is FDA approved, but is very infrequently used.1,5 Direct transmyocardial laser revascularization was studied in several RCTs and is FDA approved, but the largest trial of percutaneous transmyocardial laser revascularization with a placebo/sham control did not show any benefit and a possible signal of harm.6 Earlier unblinded trials examining surgical transmyocardial laser revascularization reported a benefit in angina relief, but the operative mortality rate was in the range of 3% to 9%. The 2012 ACC/AHA stable ischemic heart disease guideline assigned a Class 2b recommendation to transmyocardial laser revascularization. Based on a thorough review of this evidence, the writing committee feels a recommendation is no longer warranted.7

Recommendation-Specific Supportive Text

1 MUST-EECP (Multicenter Study of Enhanced

External Counterpulsation) did not study refractory angina.1 This therapy has evolved for use in patients with no other options, but the evidence base supporting this shift is inadequate, consisting of observational studies and small RCTs. Enhanced external counterpulsation was a Class 2b recommendation in the 2012 ACC/AHA stable ischemic heart disease guideline, and this was reaffirmed in the 2014 focused update.2,8 No interval data are available that warrant a change in this recommendation. Enhanced external counterpulsation has limited availability and appears to be used primarily in patients who remain symptomatic and without other therapeutic options.

4.3.8 Chelation Therapy

Synopsis Chelation therapy refers to the therapeutic use of intravenous infusions of disodium EDTA.1 Chelation has been used since the 1950s as a treatment for CCD, based until recently on anecdotal reports of benefit. EDTA avidly

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