The perioperative management of DAPT and OAC in patients with AF candidates to surgery early after coronary stenting is challenging, because a balance between the competing risks of thromboembolism (after interruption of OAC), cardiac events (after interruption of antiplatelet therapy), and perioperative bleeding is required. Both ischemic and bleeding events are known to adversely affect survival, and therefore an inadequate or excessive antithrombotic therapy may contribute to higher mortality [6]. Thus, a careful stratification of the patient’s risk profile for bleeding and thrombotic events (related to either in situ coronary thrombosis or cardiac thromboembolism) appears crucial. This assessment, in particular, also includes the type of operation in addition to the persistent indication for both antiplatelet therapy and OAC and to patient-specific factors predisposing to either bleeding or thrombosis.

As regards the risk of bleeding, surgery can be classified as high risk (i.e., 2–4 % two-day risk of major bleeding) or very low/low risk (i.e., 0–2 % two-day risk of major bleeding) [7] (Table 10.5). Furthermore, specific patient-related factors, including advanced age, low body weight, uncontrolled hypertension, reduced liver and/or kidney function, history of bleeding, and concomitant antithrombotic medications, should be considered when stratifying the surgical risk of bleeding [8].

As regards the risk of cardiac ischemic events, it has been established that premature discontinuation of DAPT is associated with an increased occurrence of stent thrombosis, a serious complication with mortality rates of 20–45 % [9–12]. The magnitude of the risk essentially depends on the timing of discontinuation and on the type of stent implanted. Moving away from the time of coronary intervention, the risk of perioperative death, myocardial infarction, and stent thrombosis has been shown to decrease from 30 % in the first month (regardless of the type of stent implanted), to 10–15 % between 2 and 6 months, and to <10 % after 6 months [13–17]. Early stent thrombosis (i.e., in the first 30 days after PCI) (Table 10.6) occurs with both bare-metal stents (BMS) and DES and may be related to residual target lesion thrombus or dissection, stasis, or stent underexpansion [18]. Late stent thrombosis (i.e., between 1 month and 1 year after PCI) and very late stent thrombosis (>1 year after PCI) are most often observed in DES, especially with early-generation devices (Table 10.2), and thought to be related to incomplete healing or inadequate neo-intimal coverage [19]. Independently of stent thrombosis, other patient-related and procedure-related predictors of further cardiac ischemic events in patients undergoing PCI include intervention for an acute coronary syndrome (ACS), concomitant diabetes mellitus, presence of diffuse coronary artery disease, implantation of small stents or long/multiple stents, intervention for in-stent restenosis, and large areas of jeopardized myocardium [20, 21]. Of note, the risk of recurrence of major cardiac events after an ACS is higher in the first weeks.

Optimal duration of DAPT after PCI is currently a matter of debate. In patients undergoing coronary revascularization for ACS, DAPT is recommended for 1 year, irrespective of the stent type [5, 22], with the aim to decrease the occurrence of re-infarction and cardiovascular mortality related to either stent thrombosis or events unlinked to the target vessel (i.e., multifocal coronary plaque instability, progression of coronary atherothrombosis) [23]. On the other hand, in the setting of stable coronary artery disease, a routine prolongation of DAPT beyond 6 months after new-generation DES implantation cannot be recommended, given the well-established risk of bleeding and the lack of evidence that extended duration DAPT may further prevent ischemic events [22]. Recent data with new-generation zotarolimus-eluting and everolimus-eluting stents suggest that even a shorter DAPT duration (i.e., 3 months) does not expose the patient to higher incidence of stent thrombosis [24–26]. However, to date a 3-month (or shorter) duration of DAPT after new-generation DES implantation should be reserved for patients at high risk of bleeding or requiring OAC [5]. Additional data are needed to confirm and definitely extend this strategy in routine clinical practice.

When a patient on DAPT is undergoing surgery, the risk of bleeding inherent to surgery and individual patient should guide the management of antiplatelet therapy. DAPT should not be withdrawn for surgery at very low bleeding risk (Table 10.5), and aspirin should be continued in the large majority of surgical interventions [5]. Interruption of aspirin from 7 days prior to surgery at high bleeding risk may be considered only in patients who are not considered at high risk of cardiovascular events [27]. Current guidelines recommend before cardiac and noncardiac surgery interrupting clopidogrel and ticagrelor for at least 5 days and prasugrel at least 7 days before the operation and continuing aspirin [5]. Of note however, the relationship between the time of withdrawal of antiplatelet agent and incidence of postoperative bleeding appears uncertain [28]. Also, the increase in surgical blood loss associated with any single antiplatelet agent as well as DAPT appears doubtfully associated with patient mortality in orthopedic surgery [28].

After surgery, DAPT should be resumed, if possible, within 24 h including a loading dose [5]. Using low-molecular-weight heparin (LMWH) or unfractionated heparin as a bridging therapy is not recommended, as heparins do not have antiplatelet properties and could even increase platelet reactivity. In patients at high risk of cardiovascular events, such as those with ongoing myocardial ischemia and/or complex anatomy (e.g., left main or severe, proximal multivessel disease), candidates to early bypass surgery, withdrawal of clopidogrel is not recommended, and these patients should undergo the operation while on DAPT with special care to hemostasis [5]. Only in patients undergoing cardiac operations with very high bleeding risk, such as redo bypass surgery or combined interventions of bypass plus valve surgery, it may be reasonable to withhold clopidogrel for 3–5 days before surgery (i.e., even in patients with active myocardial ischemia), and bridging strategies can be considered [5].

In general, DAPT interruption should be evaluated on an individual basis considering the bleeding risk of surgery, the patient’s cardiac risk profile (also including the time interval from PCI), and the type of stent. In patients on DAPT after coronary stenting candidates to operation/procedures at low bleeding risk, the P2Y₁₂ antagonist is generally interrupted if the cardiac ischemic risk is deemed to be low and the intervention, if possible, deferred if the ischemic risk is high. In patients undergoing high bleeding risk surgery who are also at high risk of ischemic events and in whom cessation of antiplatelet therapy is considered to be too hazardous (i.e., within the first weeks after stent implantation), it may be considered to switch from clopidogrel 5 days before surgery to a reversible antiplatelet agent with a short half-life, such as continuous infusion of the glycoprotein IIb/IIIa inhibitors tirofiban or eptifibatide [5] (Fig. 10.3). In an observational experience, such protocol has indeed been shown effective and safe [29]. Another emerging approach would consider the use of cangrelor, an intravenous antagonist of the P2Y₁₂ receptor characterized by rapid, potent, predictable, and reversible platelet inhibition with prompt offset of effect, but the lack of reliable efficacy and safety data makes this option still needing validation [30]. In common with glycoprotein IIb/IIIa inhibitors, cangrelor shares potency, rapid onset of action, and consistent platelet inhibition effects [31]. Short-acting glycoprotein IIb/IIIa antagonists (tirofiban and eptifibatide), however, have a slower offset of action, requiring at least 6 h to return to baseline platelet function, which is conversely achieved within 1 h after stopping cangrelor [31].