**9. Ischemia-guided strategy versus early invasive strategies**

#### **9.1. Rationale and timing for early invasive strategy**

There was a reduction in definite stent thrombosis with ticagrelor in the NSTE-ACS subgroup. In addition to increased rates of minor or non-CABG-related major bleeding events with ticagrelor, adverse effects included dyspnea (without bronchospasm), increased frequency of

All patients should be given dual antiplatelet therapy with a P2Y12 receptor inhibitor in addition to aspirin. If the patient is intolerant of aspirin or it is otherwise contraindicated, a P2Y12 receptor inhibitor can be given instead of aspirin, but two different P2Y12 receptor inhibitors should not be given together. P2Y12 receptor inhibitors can reduce mortality and morbidity, but they are associated with an increased risk of bleeding [113, 114]. Ticagrelor and prasugrel are newer P2Y12 agents, which trials have shown to have a faster onset of action and greater efficacy compared with Clopidogrel [1, 115]. However, the risk of bleeding is also greater with

Clinicians need to tailor therapy to strike a balance between a newer agent that may have a faster onset of action and greater antiplatelet effect, but could potentiate bleeding (especially in those with prior TIA or stroke). Regardless of which P2Y12 receptor inhibitor is chosen, a loading dose should be given as soon as possible in most patients and then a maintenance

Anticoagulation therapy (subcutaneous low molecular weight heparin, intravenous unfractionated heparin, or the alternative agents fondaparinux or bivalirudin) should be started on earliest recognition of NSTEMI. The anticoagulant is used in conjunction with antiplatelet therapy already started (i.e., aspirin and a P2Y12 receptor inhibitor). If fondaparinux is used during angiography/PCI, guidelines recommend that UFH be used in addition [1].

Anticoagulation should not be given if there are contraindications like major bleeding, history

The antiplatelet and anticoagulation regimens should be started before the diagnostic angiogram. Triple antiplatelet therapy, in which an intravenous GP IIb/IIIa inhibitor is added to a P2Y12 receptor inhibitor, aspirin, and anticoagulation, can be considered for high-risk patients; however, it should be avoided in patients at high risk of bleeding [1]. Although guidelines recommend the use of GP IIb/IIIa inhibitors in NSTEMI, the level of evidence for their routine use

Anticoagulation treatment should be added to aspirin and a P2Y12 receptor inhibitor at the earliest recognition of NSTEMI and continued for at least 48 h to hospital discharge and/ or until symptoms abide and objective markers demonstrate a trend toward normal [121]. Agents include subcutaneous LMWH, intravenous UFH, or fondaparinux, according to clini-

is weak at best, particularly as results from randomized trials are conflicting [119, 120].

asymptomatic ventricular pauses and increases in uric acid [109, 111, 112].

these two P2Y12 agents compared with Clopidogrel [116, 117].

of adverse drug reaction or heparin-induced thrombocytopenia.

dose continued for a minimum of 12 months [118].

**7.5. Anticoagulation**

74 Myocardial Infarction

**8. Conservative approach**

cian choice.

Once initial management is instigated, the decision should be made as to whether the patient requires treatment using an invasive or noninvasive approach. The decision to pursue an invasive approach or medical management is made on an individual basis [122]. Invasive strategy carries risks but the benefit includes diagnostic accuracy, risk stratification and revascularization. The timing for coronary angiography and the selection of the revascularization modality depend on numerous factors, including clinical presentation, comorbidities, risk stratification, presence of high-risk features specific for a revascularization modality, frailty, cognitive status, estimated life expectancy and functional and anatomic severity as well as pattern of CAD. Guidelines recommend that high-risk patients routinely undergo early (12–24 h) coronary angiography and angiographically directed revascularization if possible unless patients have serious comorbidities, including cancer or end-stage liver disease, or clinically obvious contraindications, including acute or chronic (CKD 4 or higher) renal failure or multi-organ failure [1, 123, 124].

#### **9.2. Routine invasive coronary angiography**

Invasive coronary angiography allows to confirm the diagnosis of ACS related to obstructive epicardial CAD, to guide antithrombotic treatment, identify the culprit lesions and assess the suitability of coronary anatomy for PCI or CABG. Routine invasive strategy in NSTEMI has been shown to improve clinical outcomes and lower risk of death, reduce recurrent ischemic episodes, subsequent rehospitalization and revascularization [125–127].

Urgent and immediate angiography is indicated if patients do not stabilize with intensive medical treatment [1]. Guidelines recommend that an invasive approach is appropriate if any of the following high-risk features are present [1, 15]:


#### **9.3. Pattern of coronary artery disease**

Angiographic patterns of CAD in NSTEMI patients are diverse, ranging from normal epicardial coronary arteries to a severely and diffusely diseased coronary arteries. Up to 20% of patients with NSTE-ACS have no lesions or non-obstructive lesions of epicardial coronary arteries, while among patients with obstructive CAD, 40–80% have multivessel disease [128–130].

prevent ischemic events that could occur while the patient is awaiting a delayed procedure [147]. Alternatively, by treating a patient with intensive antithrombotic therapy and delaying intervention for several days, procedure-related complications might be avoided with intervention on a more stable plaque [148]. Thus, the question of when to intervene in patients with acute coronary syndromes without ST-segment elevation has not been definitively answered. **Immediate invasive strategy** (<2 h from hospital admission) is recommended in very-highrisk NSTE-ACS patients with intent to perform vascularization because of the poor short- and

Non-ST Elevation Myocardial Infarction: Diagnosis and Management

http://dx.doi.org/10.5772/intechopen.76241

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**Early invasive strategy** (<24 h): Early invasive strategy is defined as coronary angiography performed within 24 h of hospital admission. Multiple studies showed no significant difference between early or delayed intervention groups in the rate of death, MI, stroke or major

In the early versus delayed invasive intervention in acute coronary syndromes clinical trial, prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (GRACE risk score > 140) but not in the two thirds at low-to-intermediate risk (GRACE risk score ≤ 140) [129]. Early invasive strategy is recom-

**Delayed invasive strategy** (<72 h): This is the recommended maximal delay for angiography

Patients with no recurrence of symptoms and none of the risk criteria (low risk patient), a noninvasive stress test preferably with imaging for inducible ischemia is recommended before

A conservative, early medical management strategy may be appropriate in patients with a low risk score, such subpopulations may not benefit from early invasive management especially low-risk women with NSTEMI [123, 124, 126]. Older patients may be considered at high risk for invasive approach regarding complications, but the benefit may be satisfactory from such approach in this subgroup [153–155]. Patients in whom an invasive strategy may be withheld by the treating physicians may include very elderly or frail patients, patients with comorbidities such as dementia, severe chronic renal insufficiency, or cancer and patients at high risk of bleeding complication. Ultimately patients care should be individualized and left

In the medically managed NSTE-ACS patients, the CURE study demonstrated that treatment with clopidogrel in addition to aspirin for 3–12 months, significantly lower the primary outcome (a composite of death from CV causes, non-fatal MI or stroke at 1 year) but there were

long-term prognosis if left untreated.

mended in patients with at least one high-risk criterion.

in patients with low to intermediate risk [127, 149].

bleeds [130, 149–151].

**9.6. Selective invasive strategy**

**9.7. Conservative treatment**

deciding on an invasive strategy [152].

at the discretion of the treating physician.

significantly more major bleeds [94].

Culprit lesions in the infarct-related artery are more often located within the proximal and mid segments, the left anterior descending coronary artery is the most frequent culprit vessel in both STEMI and NSTEMI-ACS (in up to 40% of patients). Left main coronary artery disease may be the underlying condition in 10% and a failure of bypass graft in 5% [128–132].
