III. Silent myocardial ischemia. Is there a role for screening asymptomatic patients and post-PCI patients?
A totally silent severe myocardial ischemia is uncommon (10- 15% of CAD). The more common form of silent myocardial ischemia consists of silent ischemia interspersed with symptomatic ischemia, such as angina or prior MI. Even if asymptomatic, ischemia is a strong predictor of cardiac events and mortality and may have the same prognostic significance as symptomatic ischemia.29
However, revascularization does not modify this prognosis, and screening asymptomatic patients based solely on risk factors is not indicated, nor is screening of post-PCI patients indicated. In the DIAD study, asymptomatic diabetic patients, who constitute a relatively
high-risk population, were screened for CAD with nuclear stress imaging. These asymptomatic patients actually had a low risk of cardiac events (0.6% per year), and while this risk was higher in the small subgroup of patients with moderate or severe ischemia (2.5% per year), 70% of events eventually occurred in patients with normal testing. In fact, a 0.6% event rate in 90% of the population leads to more total events than a 2.5% event rate in 10% of the population. Even if revascularization reduces the risk of late MI in this small subgroup, the benefit is nullified by the periprocedural risk of MI and by the risk of unnecessary diagnostic angiograms in patients with false positive stress tests. This explains why the event rate was similar in the screened and non-screened diabetic populations. Thus, stress testing is not generally useful in asymptomatic patients, even those at seemingly high risk, particularly if risk factors and hemoglobin A1c are well controlled (as in the DIAD study).30 These findings were corroborated by another study, wherein asymptomatic diabetic patients were randomized to coronary CTA screening vs. routine care. Coronary CTA found significant CAD (>70% stenosis) in 11% of patients and resulted in a 6% revascularization rate, which did not translate into any reduction of death, MI, or unstable angina (FACTOR-64 study).31 Moreover, the following 3 ideas argue against testing and stenting asymptomatic patients:
~75% of MIs arise from a plaque that was not obstructive (<50%) on a recent CT or coronary angiography (within the last couple of years).32 This is particularly true if the patient is asymptomatic, even more so if asymptomatic despite being active.
Atherosclerotic burden, as assessed by CT calcium scoring, is at least as good a predictor of coronary events as the presence of obstructive CAD. Stenting does not modify this major driver of outcomes, i.e., plaque burden.33
Occlusion of a stenosis>70% is far less likely to cause a large MI than occlusion of mild disease (30% vs. 75% likelihood), and far more likely to be preceded by angina as first presentation (70%). This is because chronic collaterals reduce infarct size in the former. Thus, seeking stenoses >70% is seeking the less deadly disease.34
The only valuable test in asymptomatic patients is CT calcium scoring, a powerful risk stratifier that dictates more aggressive risk factor modification, not revascularization. If stress testing is done in asymptomatic patients, the detection of severe ischemia would lead to revascularization only in extensive CAD, mainly left main disease.
Silent ischemia 6 months after PCI, even if severe, is not clearly associated with increased death or MI. In-stent restenosis is asymptomatic ~50% of the time, in which case the prognosis is very good; routine angiographic follow-up and PCI of asymptomatic in-stent restenosis does not improve outcomes compared to angina-driven PCI.35
IV. Medical therapy: antiplatelet therapy
While the combination of aspirin and clopidogrel is beneficial for up to 1 year after MI or stent placement, this combination has not shown superiority to aspirin monotherapy in stable CAD and peripheral vascular disease (CHARISMA trial). However, in a substudy of CHARISMA, patients with prior MI appeared to derive a benefit from prolonged combination therapy for up to 28 months, especially if they had disease in multiple vascular locations (e.g., MI and PAD).36 In monotherapy, clopidogrel is an alternative to aspirin and may be slightly superior in reducing coronary and cerebrovascular events with a slightly lower risk of GI bleed.37
Patients with CAD who also have an indication for anticoagulation (AF or a history of DVT) are best treated with standalone anticoagulation beyond 1 year of MI or coronary stenting (warfarin or NOAC). Anticoagulation, per se, effectively reduces coronary events, as in the modern AFIRE trial using rivaroxaban;38 in older trials, warfarin monotherapy or warfarin–aspirin combination was more effective than aspirin in preventing coronary events, at the cost of a higher bleeding risk.39
V. Medical therapy: antianginal therapy and risk factor control
Myocardial oxygen demands are related to the following four factors: inotropism, chronotropism, afterload, and preload. Each antianginal agent targets some of these factors. Nitrates and vasodilatory calcium channel blockers reduce ischemia by reducing preload and afterload, and, except in vasospastic angina, the coronary vasodilatory effect is a less important effect.
A. β-Blockers
1 In patients with established CAD and angina, β-blockers are first-line therapy as they reduce mortality in the first year after MI (class I). However, in stable CAD without prior MI or HF, or with MI>1 year, there is no evidence of mortality reduction and the main benefit is angina relief.40,41 Without angina, prior MI, or HF, the recommendation for β-blocker therapy is weak (class IIb).
2 A tight rate control <70 bpm has proven beneficial in HFrEF, but not in stable CAD, angina, HTN, AF, or HFpEF.42,43 In fact, in the SIMPLIFY trial, stable CAD patients with baseline pulse >70 bpm (most of whom had MI >3 months prior), did not derive a benefit from slowing the sinus rate with ivabradine, even when angina CCS was ≥II. Thus, tight heart rate control <70 bpm may not need to be pursued in stable CAD with normal EF, except possibly in severe angina.
3 Myocardial β1-receptors have a positive inotropic and chronotropic effect, thus increasing myocardial O2 demands. β2-Receptors mainly have vasodilatory and bronchodilatory effects, with a limited inotropic and chronotropic effect at baseline. However, the latter effect is exaggerated when β1-receptors are blocked. Thus, β2-blockade may be useful in patients requiring a comprehensive blockade of all myocardial adrenergic receptors, such as HF (carvedilol), but may induce harmful vasoconstrictive and bronchospastic effects.
4 Four types of β-blockers:Non-selective β1- and β2-blockers (e.g., propranolol).Selective β1-blockers (e.g., metoprolol, atenolol, bisoprolol). Selectivity is lost at high doses. β-Blockers with intrinsic sympathomimetic activity – β-blockade does not occur at rest, and rather occurs during catecholamine surges; these agents do not decrease mortality and are preferably avoided.β-Blockers with combined α- and non-selective β-blocker activity (carvedilol, labetalol) have a vasodilatory effect and, thus, a more pronounced antihypertensive effect. However, the α-blocking effect gets attenuated with time, particularly with labetalol.44
5 ContraindicationsBradycardia <55 bpm or symptomatic bradycardia- PR interval >0.24 s, or any second- or third-degree AV block.Decompensated HF (start β-blockers once HF is compensated).History of clinically severe asthma, even if the patient is currently stable, or actively decompensated COPD with wheezes. A low or moderate dose of a selective β-blocker, such as metoprolol 100 mg/day, may be used in stable, mild/moderate asthma.Use caution in diabetic patients with hypoglycemic episodes.
6 Doses:Metoprolol tartrate 25 mg BID titrated every 3–7 days to a target dose of 50–100 mg BID if tolerated (maximum 200 mg BID). Metoprolol succinate (Toprol
