era, high doses of β-blockers improved post-MI mortality.115 In the reperfusion era, in the absence of HF or low EF, the long-term benefit of β-blocker therapy beyond 1 year is questionable;116 β-blocker therapy still improves short-term post-MI outcomes and remains indicated for 1–3 years, low-to-medium doses being acceptable and equally beneficial in this setting (e.g., metoprolol 25–50 mg/d).73,116,117 High doses may lead to severe fatigue or bradycardia and may not be tolerated. β-blockers improve long-term mortality in the HF and EF≤40% settings, wherein they are titrated to high doses but slowly (e.g., carvedilol is started as 6.25 mg BID and doubled every 3–10 days) (CAPRICORN trial).118
2 ACE-I: while particularly indicated in hypertension or LV dysfunction, it is also useful for 6 weeks after any MI (ISIS-4 trial). In the stable phase beyond 6 weeks, if EF is normal and SBP is ≤ 130 mmHg, ACE-I therapy does not definitely improve outcomes (PEACE trial, prior MI subgroup).119 In light of the SPRINT trial, the blood pressure goal is ≤ 130 mmHg.120
3 High-intensity statin therapy is administered regardless of LDL. The LDL goal after ACS is < 60–70 mg/dl.121 Other agents can be combined with high-intensity statin if needed (e.g., PCSK9 inhibitors, ezetimibe, bile acid-binding resins, niacin).
4 Aldosterone antagonist is administered for an EF < 40% associated with any degree of clinical HF or diabetes; creatinine must be < 2 mg/dl.122
5 Proton pump inhibitors (PPIs) may inhibit CYP2C19 and thus reduce the conversion of clopidogrel to its active metabolite. PPIs were associated with increased cardiovascular events in some retrospective analyses of clopidogrel therapy. Yet, the only randomized trial that compared PPI to placebo in patients requiring clopidogrel therapy showed a reduction of GI events with omeprazole without any increase in cardiac events.123 Thus, patients who definitely need a PPI, such as patients with an established history of peptic ulcer disease, esophagitis, or GI bleed, or patients receiving a triple antithrombotic combination, are appropriately treated with a PPI. Patients with dyspepsia or reflux symptoms should not receive a PPI.Figure 1.8 Antiplatelet therapy after PCI in patients who also require anticoagulation (AF, LV thrombus) (according to ESC and North American perspective 2021).112 Warfarin replaces NOAC in mechanical valves or mitral stenosis.NSAIDs should be avoided for their known risks of renal failure, fluid retention, HTN, and GI bleed, especially in combination with aspirin and clopidogrel. Acetaminophen, local remedies (e.g., lidocaine cream), or, if needed, a short course of tramadol may be tried for osteoarthritic pain. If an NSAID is absolutely necessary, use the lowest possible dose and administer aspirin 2 hours before the NSAID.
6 Return to regular activities, including sexual activities, 1–2 weeks after NSTEMI. Patients with a large infarct and new LV dysfunction should avoid strenuous activities for 4 weeks (high arrhythmic risk during this period).
VII. Prognosis (Table 1.5)
In-hospital mortality of NSTEMI is lower than STEMI.124 However, short-term (30 days) and long-term mortality of NSTEMI approximates STEMI mortality (~3% at 30 days, ~5% at 1 year).60,62,71,124 Short-term mortality of unstable angina without positive markers or ST changes is much lower (≤ 1.7%).31,124 The risk of death or MI is 5–10% at 30 days and ~10–15% at 1 year.59,60,62,64 The risk is much lower beyond the first year (~2% per year).65,76,125,126 Half of these events are recurrences at the site of the culprit lesion, while the remaining events are related to non-culprit lesions. Adverse IVUS features (thin cap, heavy atheroma with positive remodeling, small luminal area) predict the progression of a non-culprit lesion to ACS, yet the predictive value is low (~20% progression of this lesion over 3 years).126 Angiographic stenosis > 50% in the context of ACS has up to 25% risk of progression in the ensuing 8 months.
Appendix 1. Complex angiographic disease- Moderate disease progression
A. Complex angiographic plaque
A complex plaque, i.e., a ruptured unstable plaque, is identified angiographically by being ≥ 50% obstructive (generally), along with one or more of the following features:
1 Thrombus: round intraluminal filling defect or contrast stain, i.e., persistence of contrast over a focal area even after it clears from the rest of the vessel. An abrupt thrombotic vessel cutoff may be present.
2 Plaque ulceration: hazy, usually eccentric plaque with irregular or overhanging margins (Figure 1.9).127
3 Impaired flow from distal microembolization.
Patients with NSTEMI frequently have multiple angiographically complex plaques (~40%). The culprit lesion is identified by seeking these morphological features but also by correlating with the ECG or imaging findings. In NSTEMI with multiple complex lesions, a clear single culprit may not be identified ~15-20% of the time, particularly given that the ST depression on the ECG is often not localizing.79 Multivessel PCI of multiple obstructive stenoses is particularly justified in patients with multiple complex plaques and without one clear culprit.80-83
B. Extent of CAD in patients with NSTE-ACS (Table 1.6)
C. Moderate CAD-Risk of progression of moderate CAD in NSTEMI and in stable CAD
If the coronary angiogram shows normal coronaries or minimal disease, the patient is at a very low risk of ischemic events in the ensuing 5 years and the coronary angiogram does not need to be repeated unless there is objective evidence of MI.
The coronary angiogram may show single- or multivessel moderate disease (40–70%), or severe disease (> 70%) in a small branch for which PCI is not technically possible or beneficial. The true functional significance of intermediate stenoses (40–70%) is worth assessing using fractional flow reserve (FFR) (during which the drop in flow across a stenosis is assessed using a pressure wire and maximal hyperemia). While FFR is mainly studied in stable CAD, the FAMOUS-NSTEMI trial and a large prospective European registry have shown that, in the setting of MI, PCI may be safely deferred for lesions with insignificant FFR >0.80.128,129
Table 1.5 Prognosis of NSTEMI.
| 30 days | 1 year | 5 years | |
|---|---|---|---|
| Death | 3% | 4–5% | 10% (1% per year past the first year) |
| Death or MI | 5% (early invasive) 10–14% (early conservative) | 10% (early invasive) 15% (early conservative) | 20% (2% per year past the first year) |
| Death, MI, recurrent ACS, or revascularization | 15–20% | 30% (3–5% per year past the first year) |
The most important numbers to remember are 5% death and 10% death/MI at 1 year despite PCI and optimal therapy. The rates herein provided are derived from clinical trial data. Real-world patients tend to be older with more comorbidities and more extensive