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In terms of the long term duration of DAPT, both current ESC and ACC/AHA guidelines recommend a duration of 12 months post PCI, unless there are contraindications such as an excessive risk of bleeding [3,4]. In this case, the ESC guidelines recommend consideration of stopping DAPT after six months, while the AHA guidelines do not make a specific recommendation. The AHA focused update on duration of DAPT in patients with CAD updates this with a Class IIb recommendation in the case of an excessive bleeding risk (discontinuation of the second antiplatelet may be considered after six months) [54].

The SMART‐DATE trial was a randomized, open‐label, non‐inferiority trial, randomizing 2712 patients in 31 centers in South Korea post ACS to either six months DAPT or 12 months DAPT, with predominantly clopidogrel the P2Y12 receptor of choice in approx. 80% of cases across both groups [55]. This showed that six months DAPT was non‐inferior to 12 months, albeit with a p‐value for non‐inferiority of 0.03 with a pre‐defined non‐inferiority margin of 2.0%, and a finding that MI occurred more frequently in the 6‐month group (HR 2.41; 95% CI 1.15 – 5.05; p = 0.02).

The DAPT‐STEMI trial [56], randomizing 870 patients to either 6 or 12 months of DAPT, had the advantage that it specifically looked at the STEMI population; 58% of patients were treated with prasugrel or ticagrelor, the remainder with clopidogrel. The primary outcome was a composite of all‐cause mortality, MI, revascularization, stroke, and TIMI major bleeding at 18 months. The hazard ratio for the primary endpoint was 0.73; 95% CI 0.41–1.27; p = 0.2, meeting the pre‐specified conditions for non‐inferiority. Neither statistically significant nor meaningful numerical differences were noted for the components of the composite endpoint. Note that only patients who were event free at six months were randomized.

The results of the REDUCE trial were suggestive of the acceptability of an even shorter duration of DAPT when absolutely necessary, with the randomization of 1496 patients with ACS treated with the COMBO stent to either 3 or 12 months of DAPT, showing that 3 months was non‐inferior in terms of a primary endpoint of all‐cause mortality, MI, stent thrombosis, stroke, target vessel revascularization and bleeding at 12 months (8.2% vs 8.4%, p value for non‐inferiority <0.001) [57]. In this study, the hazard ratio for MI in the three month arm crossed the midline (HR 1.18; 95% CI 0.67–2.08; p value for superiority 0.577). Of note, in contrast to the SMART‐DATE trial, approx. 60% of patients in both arms were treated with either prasugrel or ticagrelor rather than clopidogrel.

The trial of Ticagrelor Monotherapy After 3 Months in the Patients Treated with New Generation Sirolimus‐eluting stent for Acute Coronary Syndrome (TICO) [58], assessed an alternative approach. Patients with ACS, approximately one third of whom underwent primary PCI for STEMI, were randomized to receive ticagrelor monotherapy after three months DAPT, or ticagrelor based 12 month DAPT. Overall, 3056 patients in 38 centers in South Korea were randomized. The primary outcome was defined as a composite of major bleeding and adverse cardiovascular and cerebrovascular events (death, MI, stent thrombosis, stroke, or target‐vessel revascularization). The hazard ratio for the primary outcome in the ticagrelor monotherapy group was 0.66 (95% CI, 0.48–0.92; p = 0.01), driven by an increased risk of bleeding events in the DAPT group (HR 0.56, 95% CI 0.34–0.91; p = 0.02), without a significant difference in the incidence of major cardiovascular and cerebrovascular events, suggesting that this approach may be considered in those patients in whom DAPT poses an unacceptably high bleeding risk.

The Ticagrelor with Aspirin or Alone in High‐Risk Patients after Coronary Intervention (TWILIGHT) trial [59], addressed a similar question in a predominantly North American and European population of 9006 patients, however looked at an ACS population in general, rather than a STEMI population. Patients who were at high risk of bleeding or an ischemic event were initially treated with three months of ticagrelor plus aspirin, and then randomized to either ticagrelor alone or to continue ticagrelor and aspirin for one year, provided they did not have a major bleeding or ischemic event in the first three months. The primary endpoint was BARC type 2, 3 or 5 bleeding, and the composite end point of all‐cause death, nonfatal MI or nonfatal stroke was also evaluated with a noninferiority hypothesis. It found that ticagrelor alone was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin (HR 0.56 for ticagrelor alone, 95% CI 0.45–0.68; p < 0.001). The incidence of death from any cause, nonfatal MI or nonfatal stroke did not differ between groups (HR for ticagrelor alone 0.99, 95% CI 0.78–1.25; p < 0.001 for noninferiority).

The most recent network meta‐analysis looking at the duration of DAPT [60], compared short‐term (<6 month) DAPT followed by aspirin or P2Y12 monotherapy, midterm (6 month DAPT), 12 month DAPT and extended‐term (>12 months) DAPT after PCI with DES. It included 24 RCTs with 79,073 patients, assessing the co‐primary endpoint of MI and major bleeding (net clinical benefit), by means of a frequentist network meta‐analysis with a random‐effects model. In summary, this study revealed that in comparison with 12 month DAPT, short term DAPT followed by P2Y12 inhibitor monotherapy reduced major bleeding (RR for short term DAPT 0.69, 95% CI 0.50–0.96) without a significant difference in the risks of ischemic endpoints, whereas extended‐term DAPT reduced MI (RR for extended term DAPT 0.68, 95% CI 0.54–0.87) at the expense of more bleeding events (RR 1.63, 95% CI 1.15–2.30). For the ACS sub‐group specifically, extended‐term DAPT in comparison with 12‐month DAPT was associated with a reduced risk of MI (RR for extended‐term DAPT 0.42, 95% CI 0.27–0.65) without a significant risk of major bleeding. Cardiovascular and all‐cause mortality did not differ between treatment groups. Taken together, these results suggest a personalized approach to the duration of DAPT should be considered, considering individual patient‐level relative and absolute risks of bleeding and ischemia.