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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168 August 29, 2023 Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline events (12 versus 16 events per 100 patient-years [adjusted hazard ratio, 0.42 (95% CI, 0.27-0.66)]).11 A systematic review and meta-analysis of observational studies with >163 000 participants found that the PPSV23, PCV13, or both was associated with a 22% decrease in all-cause death in patients with CCD or those with very high cardiovascular risk, although the study design of some included studies led to a decreased level of design confidence.12 A retrospective observational study using the 2012–2015 US National Inpatient Sample database evaluated the combined use of pneumococcal polysaccharide vaccine (PPV) and influenza vaccine and found lower mortality rate (2.21% versus 1.03%; P=0.001) and lower cardiac arrest (0.61% versus 0.51%; P<0.001). The relative risk was 0.46 (95% CI, 0.43–0.49) in the adjusted analysis for this combined vaccination group. This group also had significantly reduced risk of mortality among those admitted with MI (relative risk, 0.46), TIAs (relative risk, 0.58), and stroke (relative risk, 0.42) compared with the nonvaccinated group.13 4.3.6 Medical Therapy for Relief of Angina Recommendations for Medical Therapy for Relief of Angina Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations 1 B-R 1 In patients with CCD and angina, antianginal therapy with either a beta blocker, CCB, or longacting nitrate is recommended for relief of angina or equivalent symptoms.*1–3 1 B-R 2 In patients with CCD and angina who remain symptomatic after initial treatment, addition of a second antianginal agent from a different therapeutic class (beta blockers, CCB, long-acting nitrates) is recommended for relief of angina or equivalent symptoms.*3–6 1 B-R 3 In patients with CCD, ranolazine is recommended in patients who remain symptomatic despite treatment with beta blockers, CCB, or longacting nitrate therapies.*7,8 1 B-NR 4 In patients with CCD, sublingual nitroglycerin or nitroglycerin spray is recommended for immediate short-term relief of angina or equivalent symptoms.*9,10 3: Harm B-R 5 In patients with CCD and normal LV function, the addition of ivabradine to standard anti-anginal therapy is potentially harmful.*11 *Modified from the 2012 ACC/AHA Multisociety Guideline for the Diagnosis and Management of Patients With SIHD.12 Synopsis Medical antianginal therapies for patients with CCD are understood to act via 2 general mechanisms: by decreasing myocardial oxygen demand or by increasing myocardial arterial blood supply.9 Beta blockers, non-dihydropyridine CCBs, and ivabradine decrease myocardial oxygen demand (via decreasing contractil- ity, heart rate, or both) while nitrates and dihydropyridine CCBs increase arterial oxygenated blood supply via vasodilatory actions. Ranolazine has a less well-defined mechanism of action, potentially by decreasing calcium overload through inhibition of the late sodium current. The overriding goal is to maximize relief of symptoms while choosing therapy that will not exacerbate comorbidities, will not have important interactions with concomitant medications and will be well tolerated. In the context of CCD antianginal therapy, the justification for their use rests fully on their effectiveness in relieving symptoms. Specific circumstances may justify choosing 1 agent over another (eg, a beta blocker in a patient with concomitant LV dysfunction). Control of symptoms may be achieved by most patients, but full freedom from angina is only achieved in 40% to 50%, depending on anginal frequency at the onset of treatment.13 Recommendation-Specific Supportive Text 1 Beta blockers have been considered the first anti- anginal to use in patients with symptomatic CCD, although the evidence basis for this prioritization is not strong. Early randomized, placebo-controlled studies found that beta blockers increased the percentage of patients free of exertional angina, reduced anginal attacks and reduced nitroglycerin consumption.1,2 A meta-analysis of 72 studies comparing beta blockers with CCBs found fewer episodes of angina per week with beta blockers and lower rates of drug discontinuation.3 No difference was observed in the rate of death or MI between the 2 drug classes. A more recent meta-analysis including only larger studies comparing beta blockers with calcium channel blockers found no difference in the primary endpoint of exercise duration.4 In randomized, placebo-controlled trials, CCBs effectively relieve angina, decrease nitroglycerin consumption, and increase exercise duration.14,15 Long-acting nitrates decrease angina and improve exercise duration.16 Non-dihydropyridine CCBs (verapamil and diltiazem) can further depress LV function and should not be used in patients with CCD and significant LV dysfunction.17 2. In patients with CCD and angina refractory to 1 agent, a combination with another antianginal agent improves symptom control.5 Non-dihydropyridine CCBs should be used with caution in patients on beta blockers because of the potential for synergistic induction or exacerbation of bradycardia and LV dysfunction. The addition of a long-acting nitrate to a beta blocker or a CCB improves exercise tolerance, reduces angina frequency and short-acting nitrate use.5 3. Two randomized, placebo-controlled studies showed that the addition of ranolazine on the background of standard anti-anginal therapy Downloaded from http://ahajournals.org by on October 7, 2026