Improvement of LV diastolic function.
Reduction of arrhythmias.
Reduction of HbA1c of ~1% in patients with HbA1c ≥8% (MERLIN analysis).
Ranolazine may be used as initial therapy in patients who do not tolerate β-blockers (alternative to CCB and nitrates), or as additional therapy in patients with persistent angina despite standard therapy.
F. Control of risk factors
1 Statin, regardless of LDL. If needed, ezetimibe or PCSK-9 inhibitor may be added to achieve LDL <70 mg/dl.
2 HTN is controlled to <130/80 mmHg (ACC and SPRINT trial).57
3 ACE-I is beneficial in CAD patients (HOPE and EUROPA trials),58 more so in cases of EF <50%, HTN, diabetes, or CKD. In CAD patients with SBP 130–140 mmHg and normal EF, ACE-I did not show any benefit (PEACE trial).59 In the early post-CABG setting (≤7 days) with normal EF and BP, ACE-I initiation did not improve outcomes and was associated with more adverse events in the first 3 months (IMAGINE trial).60
4 Control of diabetes to a Hb A1c ≤7%.
5 Smoking cessation leads to a 50% reduction of the excessive risk of MI and stroke within 1 year (mostly within 2 months). At 3–5 years, the risk approaches that of never-smokers.
VI. Indications for revascularization
The first step is to determine if the patient requires coronary angiography (Figure 3.2). The second step is to determine if the patient requires revascularization. The third step is to determine whether CABG or PCI is appropriate. The need for coronary angiography does not imply a need for revascularization once CAD is found. In fact, medical therapy is frequently appropriate in a patient with significant, even multivessel CAD (with no left main disease). Coronary angiography serves as a risk stratification tool that helps determine whether medical therapy alone is appropriate. Based on ISCHEMIA trial, coronary CTA may replace coronary angiography and may be used to exclude left main disease and proceed with conservative management even in patients with multivessel disease.
In order to benefit from revascularization, one of the following 2 features excluded from ISCHEMIA trial must be present: (1) severe refractory angina, or (2) severe left main disease, regardless of angina.19,20 Extensive 3-vessel CAD or 2-vessel CAD with proximal LAD may also benefit from CABG, but less strongly. Refractory angina is defined as frequent angina (multiple times weekly) that persists despite the use of at least two antianginal medications (or less in case of intolerance or a baseline low BP and heart rate).
Old retrospective analyses suggested that revascularization in the setting of extensive ischemia involving ≥10% of the LV was associated with a reduction of mortality; this suggested a role for ischemia assessment in guiding revascularization.61 However, the large randomized trial ISCHEMIA disproved this hypothesis. Analyses from both ISCHEMIA and COURAGE suggest that the anatomic burden of disease is a far superior predictor of death and cardiac outcomes than ischemia, even though neither one predicts a benefit from revascularization. 62,63 Ruling out left main disease via CTA or angiography appears more important than functional ischemia evaluation.
In chronic stable CAD, revascularization of single or even multivessel CAD mainly has a symptomatic value, particularly in patients with refractory angina, with no effect on survival or MI prevention.
While a significant stenosis has a higher individual risk of plaque rupture and MI (~3% per year) than a non-significant plaque (<0.5%) (COURAGE, ISCHEMIA, FAME trials),19,64–66 non-significant plaques are much more common throughout the coronary vasculature than significant plaques; therefore, MI or ACS often occurs over a lesion that is <50% stenotic: these lesions were responsible for 2/3 of ACS events upon long-term follow-up in PROSPECT trial and coronary CT studies. 32,33,67 In FAME-2 trial, patients with insignificant FFR had a very low risk of MI from individual plaques, but the summation MI risk was still ~2% at 8 months and 8% at 5 years.28,66 While stenting reduces the risk of spontaneous events arising from a significant plaque, the benefit is negated by periprocedural myocardial infarction (~2.5%), stent thrombosis and severe restenosis, which explains why stenting stable CAD does not reduce the overall MI risk.66 Moreover, a larger number of events continues to arise from non-significant plaques.
VII. CABG and CABG vs. medical therapy
CABG is the only revascularization modality shown to improve survival in the high-risk subsets of stable CAD. In a meta-analysis that included the three classic trials of CABG vs. medical therapy, the Coronary Artery Surgery Study (CASS), the European Coronary Surgery Study (ECSS), and the VA study, CABG reduced mortality by 40–50% in the following groups:68
Left main disease (mortality reduction of ~75%).
Three-vessel CAD, or one- or two-vessel CAD involving the proximal LAD. CABG is beneficial in these patients irrespective of LV function, but more so in the case of mild LV dysfunction with EF 35–50% or evidence of moderate/severe ischemia on stress testing (i.e., make sure CAD is functionally significant).
CABG was beneficial in the classic trials despite a 25% crossover to CABG in the medical therapy arm at 5 years, implying that the absolute CABG benefit is even higher. This CABG benefit was seen irrespective of symptom status and extended to asymptomatic patients. Note that the survival benefit in stable CAD does not emerge until 2 years after CABG, partly because of the early surgical hazard; thus, CABG is an appropriate therapy in patients who are otherwise likely to have a good longevity. CABG is expected to be beneficial sooner in patients with unstable CAD. Those trials were done in the 1970s, at a time when CABG technique was suboptimal (LIMA was not routinely used, which explains why the survival advantage of CABG gradually narrowed beyond 10 years). But in those trials medical therapy was also suboptimal (mainly consisting of β-blockers, with very limited use of aspirin and no statin). In fact, in the CABG stratum of the modern BARI 2D trial, initial CABG did not reduce the mortality of diabetic patients with multivessel, non-left main disease (vs. initial medical therapy). Same results were replicated in ISCHEMIA trial. Thus, the only absolute indication for CABG in the stable CAD setting is left main disease, not 3-vessel or proximal LAD disease.
The above trials excluded patients with severe LV dysfunction (EF <35%). In patients with severe ischemic LV dysfunction (EF <35%), no or mild angina, and no severe HF, CABG improved death and cardiovascular hospitalizations at 10 years in the STICH trial.69,70The benefit was, however, not dramatic (~20% reduction of cardiovascular death). Once again, the benefit did not emerge until 2 years after CABG. This benefit was irrespective of viability testing.
CABG may also be performed for single- or two-vessel CAD not involving the LAD, if PCI is not technically feasible and the patient has refractory, severe angina. The value of a single- or two-vessel CABG to a non-LAD vessel is mainly symptomatic.
The well-known benefit of CABG in diabetic patients is seen in CABG vs. PCI trials, rather than in the above trials of CABG vs. medical therapy.
VIII. PCI and PCI vs medical therapy
General PCI indications and pitfalls- Consider the
