Ticagrelor with or without Aspirin in High-Risk Patients after PCI

Abstract

BACKGROUND Monotherapy with a P2Y 12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, −0.06 percentage points; 95% CI, −0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.

The efficacy and safety of P2Y12 inhibitor monotherapy in patients after percutaneous coronary intervention

“…As described in Figure 1 patients met our eligibility criteria. [11][12][13][14] Of these, 14 530 patients were randomized to monotherapy with a P2Y12 inhibitor, whereas 14 599 patients were randomized to standard dual antiplatelet therapy. Four trials tested P2Y12 inhibitor monotherapy after 1 to 3 month of DAPT vs P2Y12 inhibitor plus aspirin ( Table 1).…”

“…Nevertheless, in the subgroup analysis of this study, there was no significant interaction between the type of P2Y12 inhibitors and the treatment effects of the two antiplatelet regimens on the bleeding events. The TWILIGHT study, enrolled patients undergoing PCI who are at high risk for ischemic or hemorrhagic complications, was associated with a 51% lower risk of bleeding. In contrast to these three studies, the results of The GLOBAL LEADERS trial showed that DAPT for 1 month followed by 23 months of ticagrelor alone did not reduce the incidence of bleeding than the traditional DAPT treatment regimen .…”

Platelet Function Test Use for Patients with Coronary Artery Disease in the Early 2020s

“…It is of note that the switched DAPT strategy was superior in terms of bleeding regardless of the initial platelet reactivity [73]. The recent TWILIGHT study further supported a strategy based on a shorter DAPT [74]. This study randomized more than 7000 high-risk patients who had undergone an uneventful 3-month course of DAPT after PCI using ticagrelor, to either continue with DAPT for an additional 9 months or stop aspirin.…”

Early Aspirin Discontinuation Following Acute Coronary Syndrome or Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In these circumstances, the benefit of sustained DAPT may translate into a smaller absolute ischemic event risk reduction, which might be potentially outweighed by the associated higher risk of bleeding [6]. Since aspirin yields limited additional platelet inhibition when associated with P2Y 12 inhibitors, aspirin-free strategies have been evaluated in several recent randomized controlled trials enrolling ACS or PCI patients; in some of these studies patients also had an indication for chronic oral anticoagulation (OAC) [7][8][9][10][11][12][13][14][15][16][17][18][19]. Most of these trials (but not all) reported lower rates of bleeding without aspirin, but all of them were underpowered as to properly evaluate the associated ischemic risk.…”