Practical Cardiovascular Medicine. Elias B. Hanna

thus have higher event rates.

      Intracoronary imaging with OCT or IVUS is also useful to assess moderate NSTEMI lesions. In fact, in NSTEMI, the question is not only whether the lesion is functionally significant but whether the lesion is anatomically significant and likely to acutely progress (e.g., plaque rupture, thrombus). The goal of therapy in NSTEMI is to reduce the high risk of recurrent infarction rather than just improve angina; hence, the assessment of anatomy is more valuable in NSTEMI than in stable CAD. A thrombotic lesion that is not functionally significant at one point in time may still progress within days or weeks. In addition, the true lumen of a ruptured or ulcerated plaque may be much narrower than its angiographic appearance (contrast seeps through the planes of the ruptured plaque beyond the true lumen, giving the impression of a large lumen that is, nonetheless, hazy).

Figure 1.9 The concentric and eccentric lesions with smooth borders are predominantly seen in stable CAD, while the lesions with irregular or overhanging borders are predominantly seen in ACS. Haziness may be due to an unstable fissured plaque, with contrast faintly seeping through the fissures of the plaque beyond the true lumen; it may also be due to concentric calcium surrounding the lumen and does not necessarily imply instability.

Table 1.6 Angiographic findings in NSTE-ACS and rates of revascularization.^59-61

Angiographic findings	Revascularization
Insignificant disease or normal coronaries ~10% 1-vessel CAD ~30% 2-vessel CAD ~30% 3-vessel CAD ~30% Left main disease ~10%	PCI in ~60–70% CABG in ~10–15% No revascularization in ~30%

      Even in NSTEMI patients whose symptoms and electrocardiographic ischemia are quickly stabilized with medical therapy, an untreated culprit stenosis of > 50% has a 25% chance of progression within 8 months, mostly to a total occlusion, more so when the lesion has a complex appearance; note that this study was performed before the era of widespread statin and ADP receptor antagonist use.¹³⁰

      Conversely, the progression is much slower in stable CAD stenoses >50% (<10% progression rate per lesion at 1.3 years with <2-3% ACS) (COURAGE trial).¹³¹

      Non-culprit stenoses have a slow progression in both MI or stable CAD: the summation risk of angina progression from all lesions is ~6% at 1 year and ~10% at 3 years of follow-up, mostly arising from lesions <50%, more so in the presence of complex angiographic or IVUS features, with only 1% death/MI from all these lesions at 3 years (PROSPECT trial).^126,130

Appendix 2. Women and ACS, elderly patients and ACS, CKD

      A. Women and ACS

In trials of initial invasive vs. initial conservative strategy, low-risk women without elevated troponin, ST changes, or high TIMI risk score had a higher risk of death/MI with an invasive strategy than a conservative strategy (significant in RITA 3, non-significant trend in FRISC II).^64,132 However, high-risk women derive a benefit from an initial invasive strategy (TACTICS, meta-analysis).^62,133 While an initial invasive strategy is not indicated in low-risk men either, a meta-analysis shows that an initial invasive strategy is not harmful to low-risk men but is harmful to low-risk women.¹³¹ This is related to the fact that women have less extensive CAD than men in general, and that in these trials of NSTE-ACS, ~24% of women vs. 8% of men randomized to an invasive strategy had no significant CAD, and even among women with elevated troponin, 15–20% had no significant CAD.^133,134 In fact, women have a higher burden of macro- or microvascular spasm. Even among women with CAD, three-vessel or left main disease is less common than among men. In addition, women have a higher bleeding risk, particularly at the vascular access site, which attenuates the benefit from an invasive strategy. Women also have a higher complication rate with CABG.⁶⁴

      Despite less extensive CAD, less positive troponin, and less common STEMI presentation relative to NSTE-ACS,¹³⁵ the mortality of women with ACS is equal to that of men, and may be higher on unadjusted analyses (GUSTO IIb analysis) or in the specific case of STEMI.¹³⁵ Women with ACS are older and have more comorbidities (diabetes, diastolic HF) than men. They have a higher BNP and a higher burden of dynamic ST changes on continuous ECG monitoring than men, indicative of a significant ischemic burden despite less CAD and less troponin rise (MERLIN-TIMI trial).¹³⁴ In fact, even among women without obstructive CAD, ~14% have dynamic ST changes on continuous ECG monitoring. Ranolazine may be of particular benefit in women with angina.¹³⁴

      B. Elderly patients and ACS

      Patients > 75 years old with ACS have double the mortality of younger patients. Elderly patients more frequently have atypical presentations with milder ST changes. While associated with a higher major bleeding risk in patients > 75 years old, an early invasive strategy drastically reduced the absolute risk of death/MI by 10% at 6 months in those inherently high-risk patients (TACTICS-TIMI-18 trial).¹³⁶ This was further confirmed in a trial that randomized octogenarian ACS patients to an invasive vs. conservative strategy, using predominantly a radial access (AFTER EIGHTY).¹³⁷ However, this benefit may only apply to carefully selected elderly patients with limited comorbidities and bleeding risk, similar to the patients recruited in clinical trials. A careful access (radial) and antithrombotic strategy may maximize the benefit from an invasive strategy, and GPI should be avoided if possible.

      C. CKD

      Approximately 20–40% of patients presenting with NSTEMI have CKD. Although the bleeding risk is increased in renal failure regardless of the anticoagulant used, bivalirudin (in patients undergoing PCI) and fondaparinux (outside PCI) are associated with less bleeding than UFH or enoxaparin in patients with mild or moderate renal failure.⁵⁹ When GFR is < 30 ml/min, UFH or dose-adjusted enoxaparin are approved for use; the bleeding risk is, however, higher with enoxaparin at any stage of renal failure, including GFR 30-60 ml/min, and UFH is preferred.¹³⁸ A GPI is best avoided in CKD; if used, the bolus and infusion doses of eptifibatide are reduced in half when GFR is < 50 ml/min.

      CKD patients are inherently high-risk patients. Despite the high prevalence of CKD, large randomized trials that have addressed the benefit of an invasive strategy in ACS have excluded patients with advanced CKD. Subgroup analyses of these trials suggest a benefit of an invasive strategy in patients with mild CKD, and observational data suggest that patients with mild or moderate CKD (GFR 30–60 ml/min) derive a benefit from an invasive strategy, which makes sense, considering the inherently high ischemic risk of these patients.^139,140 This benefit may extend to carefully selected high-risk patients with CKD stages 4 or 5, who, nonetheless, have a higher risk of bleeding and renal and HF complications peri-PCI.¹⁴⁰

Appendix 3. Bleeding, transfusion, patients on chronic warfarin or NOAC, gastrointestinal bleed

      A. The negative impact of bleeding

      In the context of ACS or PCI, the occurrence of major bleeding has at least the same prognostic impact as the occurrence of a new MI.^141,142 Compared with patients without bleeding, patients who experience bleeding have a much higher in-hospital but also late mortality (up to 5× higher). In fact, while bleeding is rarely fatal by itself, bleeding strikingly increases the risk of MI, coronary thrombosis, and ischemic events through the following concepts: (i) antithrombotic therapy may need to be temporarily withheld; (ii) bleeding