Practical Cardiovascular Medicine. Elias B. Hanna

vasospasm) may also be performed.18,20 The long-term prognosis is generally good.

      2 ~15% have significant CAD but are not deemed candidates for revascularization. These patients may have limited CAD in a small branch or a distal coronary segment that supplies a small territory, which is therefore not considered an appropriate revascularization target. The majority of these patients, however, have extensive and diffuse CAD, more extensive than patients undergoing PCI, along with more comorbidities (history of CABG, MI, PAD, stroke, CKD, anemia).25,85 These patients are not considered candidates for PCI or CABG because of the diffuseness of the CAD, the small diameter of the involved vessels (< 2 mm), the lack of appropriate distal targets for CABG, or the medical comorbidities. Their mortality is high, 3–4 times higher than the mortality of patients who are candidates for revascularization (~20% at 3–4 years).25,85,86

      In patients with insignificant CAD whose angiographic or IVUS appearance suggests stabilized plaque rupture, long-term aggressive medical therapy is indicated (including 1 year of clopidogrel or ticagrelor). This also applies to the patients with significant CAD who do not get revascularized.

VI. Discharge medications in NSTEMI

      A. Antiplatelet and anticoagulant therapy

      1 Aspirin 81 mg/day. Chronically, the low dose is as effective as higher doses with a lower risk of GI bleed, even in patients who undergo coronary stenting.

      2 ADP receptor antagonist (clopidogrel 75 mg/day, prasugrel 10 mg/day, or ticagrelor 90 mg BID) (Figure 1.7).Even if PCI is not performed, prescribe clopidogrel or ticagrelor for at least 1 month, and preferably 12 months. This applies to patients with significant CAD who are not revascularized, but also patients with insignificant CAD when moderate disease is present or plaque rupture is believed to be the underlying trigger.⁷¹ In addition, clopidogrel is beneficial in patients who undergo CABG in the context of ACS, where clopidogrel may be started a few days after CABG.⁸⁷ In the absence of stenting, the ADP receptor antagonist is more readily stopped if needed (bleeding, surgical procedure).If PCI is performed, prescribe clopidogrel, prasugrel, or ticagrelor for 12 months, regardless of whether a bare-metal stent (BMS) or a drug-eluting stent (DES) is used. Prasugrel or ticagrelor is preferred by the ACC and ESC guidelines. De-escalation to clopidogrel may be done at 1 month if the bleeding risk is high (TOPIC trial).Does a longer duration of therapy (>12 months) provide extra benefit? (Table 1.4) According to the DAPT study, which included patients with MI (26%) or stable CAD undergoing DES placement, the continued administration of a thienopyridine between 1 year and 2.5 years reduced the MI risk in half during this time frame (from 4% to 2%). MI was reduced at the stent site (stent thrombosis) but also at distant lesions, where half of the events occur. This benefit was seen despite the short study duration (1.5 years) and despite the exclusion of patients who had a recurrent coronary event in the first year, the latter likely deriving an even larger benefit from continued thienopyridine administration.⁸⁸ A benefit of prolonged therapy was also seen in a separate DAPT study addressing BMS patients. Interestingly, even beyond 1 year, and even with BMS, there was a ~1% risk of stent thrombosis after thienopyridine interruption, similar to DES. The pitfall of this prolonged therapy was an increase in bleeding, cancer diagnoses, and overall deaths (related to cancer and bleeding). Thus, continued thienopyridine therapy seems reasonable in patients who have a low bleeding risk (e.g., age < 75) and no suspicion of underlying malignancy; it is expected to be particularly beneficial in the high ischemic risk groups, such as recurrent MI, multiple complex PCIs, combined CAD + PAD, ischemic HF, or ongoing uncontrolled risk factors, such as smoking or diabetes.89,90 Another trial, CHARISMA, addressed prolonged dual antiplatelet therapy regardless of stenting and showed that patients with a prior MI, as opposed to stable CAD, benefited from extended dual antiplatelet therapy for up to 28 months, whether PCI was performed or not; the benefit was larger in patients with a prior MI and PAD.⁹¹Figure 1.7 Duration of dual antiplatelet therapy (DAPT) according to ACC guidelines.Table 1.4 Long-term therapy >12 months may be considered based on the following: DAPT score of mostly clinical variables (ischemic risk, long-term): ⁸⁹(1) age>75: -2; 65-75: -1;<65: 0(2) smoking: +1; (3) diabetes: +1;(4) stent in the setting of MI: +1; (5) recurrent event (prior PCI or MI): +1;(6) stent <3 mm: +1; (7) HF or EF<30%: +2; (8) SVG stent: +2. DAPT score ≥ +2 favors DAPT> 12 months, while age >75 argues against it. PAD and CKD are additional markers of ischemic risk.¹¹² Anatomical complexity, i.e., any of the following, especially ≥ 3 (thrombotic risk, mostly early): ⁹⁰ 3 vessels treated, ≥3 stents implanted ≥3 lesions treated, stent length >60 mm, bifurcation with 2 stents implanted, chronic total occlusion, left main, atherectomyConversely, is earlier interruption acceptable? The ADP receptor antagonist may be safely interrupted at 1 month with BMS, at 3 months with DES in the stable CAD setting,92-102 and at 6 months with DES in the ACS setting (DES registries and PRODIGY trial).92,93,95–102 Upon interruption between 6 and 12 months, there is a small risk of MI that is, nonetheless, likely similar to the low and steady risk at >12 months’ interruption, not higher.90,93,96,103 For those patients deemed at high risk of stent thrombosis or recurrent MI, the interruption of the ADP receptor antagonist is limited to < 7–10 days. In fact, the median time from clopidogrel interruption to stent thrombosis, when it rarely happens in the 1–6-month time interval after stent implantation, is 13.5 days.104,105Several studies even suggest that 1–3 months of DAPT, followed by clopidogrel or ticagrelor monotherapy (aspirin discontinuation), may be sufficient after DES in both stable or unstable CAD (MASTER-DAPT, STOP DAPT-2 and SMART-Choice trials with clopidogrel).98-101 This is particularly true for ticagrelor monotherapy in ACS and complex anatomy; aspirin beyond 3 months nearly doubled major bleeding with no ischemic benefit (TWILIGHT and TICO trials).¹⁰² Three trials only used 1 month of DAPT in high-bleeding risk PCI patients, mostly ACS, and showed superior safety with DES vs BMS despite this short DAPT.98,99 As such, ESC guidelines allow, in ACS, a shorter DAPT duration of 3 months if high bleeding risk (class IIa).

      3 Oral anticoagulant (Figure 1.8). In patients with AF or LV thrombus who undergo stent placement, the question is whether they need to receive a triple combination of aspirin, clopidogrel, and oral anticoagulant. The triple therapy has a 4× higher major bleeding risk than aspirin + warfarin (12% vs. 3–4% yearly bleeding risk).¹⁰⁶ According to WOEST (using warfarin), PIONEER-AF (rivaroxaban), RE-DUAL PCI (dabigatran), and AUGUSTUS (apixaban) trials, patients with AF undergoing PCI (mainly DES, ACS in 50-60% of patients) may be treated with the dual combination of clopidogrel and one anticoagulant, with no aspirin therapy beyond the first 1-7 days of PCI.107-111 In fact, the dual combination clopidogrel-anticoagulant was much safer than the triple combination aspirin-clopidogrel-anticoagulant, used for 1-6 months, with a similar protection from MI and stent thrombosis, significant bleeding reduction in all trials, and mortality reduction in WOEST. The combined inhibition of the ADP pathway with clopidogrel and the thrombin pathway with anticoagulation may lessen the importance of cyclooxygenase inhibition with aspirin. As a result, initial double therapy (clopidogrel+ apixaban, rivaroxaban, edoxaban, dabigatran, or less favourably warfarin) is currently recommended and preferred over initial triple therapy in all patients by the North American consensus.¹¹² Triple therapy, for 1 month only, may be considered in patients who have a combined high ischemic risk/low bleeding risk (in AUGUSTUS trial, triple therapy reduced the 30-day ischemic risk by 0.9%, while increasing the bleeding risk by ~0.9%; beyond 1 month, triple therapy only caused increased bleeding, with no ischemic benefit).Beyond one year of PCI or MI, single therapy with oral anticoagulant is recommended (no aspirin nor clopidogrel) and appears to reduce mortality, bleeding and cardiovascular events compared to anticoagulant+single antiplatelet agent (AFIRE trial with rivaroxaban, and registry data).113,114

      B. Other therapies

      1 β