In the acute phase of NSTE-ACS, anti-ischemic drugs should immediately be given for both chest pain and ischemia relief. Accordingly, early initiation of beta-blocker treatment, or continuation of chronic beta-blocker therapy, is recommended, unless Killip class ≥3 or contraindications to beta-blocker therapy are present [1] (Table 7.1). Sublingual and/or intravenous (IV) nitrates are also recommended [1] (Table 7.1).

Given the pathophysiology of NSTE-ACS, generally involving nonocclusive thrombus formation at the site of a ruptured atherosclerotic plaque, early and effective antithrombotic therapy, including both platelet and thrombin inhibition, is warranted [1]. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y₁₂ receptor inhibitor, including ticagrelor, prasugrel, or clopidogrel, is recommended soon after the diagnosis (Table 7.1), to be continued for 12 months, unless there are contraindications, such as excessive risk of bleeding [1]. Parenteral anticoagulation is recommended at the time of NSTE-ACS diagnosis to inhibit thrombin generation and/or activity [1] (Table 7.1). Either subcutaneous fondaparinux or enoxaparin or intravenous bivalirudin or unfractionated heparin (UFH) should be given [1] (Table 7.1).

In NSTE-ACS patients, stratification of short-term ischemic and bleeding risk should be performed at presentation based on the combination of clinical history, symptoms, vital signs, other physical findings, ECG, and laboratory results, including troponin test [1]. Established risk scores, including GRACE (Table 7.2) and CRUSADE (Table 7.3), should be used for such early stratification [1]. In-hospital invasive coronary angiography (CORO) is generally performed in patients with NSTE-ACS to (a) confirm the diagnosis; (b) identify the culprit lesion; (c) establish the indication for coronary revascularization, while assessing at the same time the suitability of coronary anatomy for percutaneous coronary intervention (PCI) and/or coronary bypass (CABG) surgery; and (d) stratify the patient’s short- and long-term risk [1]. Such routine invasive strategy has been shown to improve clinical outcomes and reduce recurrent ACS episodes, subsequent rehospitalization, and revascularization compared to selective invasive strategy (where invasive coronary angiography and revascularization when indicated are driven by nonresponsiveness to initial medical treatment and/or early recurrence of ACS) [1]. Timing of invasive strategy should be based on the early risk of adverse events, as estimated by the presence or not of distinct features, namely, (1) within 2 h (analogous to ST-elevation myocardial infarction management) for very-high-risk patients, (2) within 24 h for high-risk patients, and (3) within 72 h for intermediate-risk patients (Table 7.4). In low-risk patients, that is, with none of the characteristics qualifying the above mentioned categories, a noninvasive stress test (preferably with imaging) for inducible ischemia is recommended before deciding on invasive strategy [1]. While percutaneous coronary intervention (PCI) with stent should be performed on the culprit lesion and generally also on all significant lesions in multivessel disease patients, conservative treatment should be offered to those patients who show either nonobstructive coronary artery disease, coronary artery disease not amenable to revascularization, or normal angiogram [1].

When PCI is performed, the radial vascular approach and the use of new-generation drug-eluting stents (DES) (Table 7.5), generally allowing a duration of DAPT of only 6 months or less, are recommended, to reduce the overall risk of bleeding [1].

AF complicates the course of ACS in approximately 10 % of cases [2]. Possible underlying mechanisms of AF in this setting include atrial ischemia or infarction, acute hypoxia or hypokalemia, pericardial inflammation, increased left ventricular (LV) diastolic pressure and left atrial pressure, and hemodynamic impairment secondary to LV dysfunction [3]. New-onset AF in ACS is associated with an increased risk of in-hospital and long-term mortality [3]. Also, AF complicating ACS is associated with an increased risk of subsequent “spontaneous” AF and also with an increased risk of ischemic stroke both during hospitalization and during follow-up, even if the AF is transient and reverses back to sinus rhythm before hospital discharge [3]. Adequate rate control represents the most important first therapeutic approach, whereas direct current electrical cardioversion should generally be reserved to patients with severe hemodynamic instability or intractable ischemia or when adequate rate control cannot be achieved with pharmacologic agents [3].

Given that patients with either permanent, persistent, or paroxysmal AF and ACS are a special subgroup with an increased risk for ischemic and embolic events, as well as bleeding complications, proper risk stratification should be promptly carried out. Based on CHA₂DS₂-VASc scoring (Table 7.6), all patients with a score ≥2 should be offered oral anticoagulation (OAC) [4]. Of note, DAPT with aspirin and a P2Y₁₂ receptor inhibitor, including ticagrelor, prasugrel, or clopidogrel, is also recommended in patients with ACS and especially when PCI-S has been performed (which occurs in over 90 % of patients with STEMI and approximately 50–60 % of those with NSTE-ACS) [3]. Stratification of bleeding risk should also be carried out in patients with AF (with or without associated ACS) by using the HAS-BLED score (Table 7.7) [3, 4]. Whereas a score ≥3 identifies patients at high risk of bleeding, the HAS-BLED score should be used not to select the antithrombotic therapy but essentially to identify patients potentially at risk of bleeding and to help identify and correct the potentially reversible bleeding risk factors (including uncontrolled hypertension, suboptimal quality of oral anticoagulation (OAC), concomitant use of aspirin or nonsteroidal anti-inflammatory drugs, and alcohol excess and/or abuse) [4, 5].