ABSTRACT
Background
Ticagrelor monotherapy after a short period of dual antiplatelet therapy (DAPT) has shown to be safe and effective after percutaneous coronary intervention (PCI), including primary PCI in ST-elevation myocardial infarction (STEMI). However, direct omission of aspirin could further reduce bleeding risk. We aimed to assess the safety of ticagrelor monotherapy directly after primary PCI regarding ischemic events, and to investigate the effect on clinical bleeding events.
Methods
In this multicenter open-label pilot study, 200 STEMI patients were 1:1 randomized to ticagrelor monotherapy versus ticagrelor plus aspirin, directly after primary PCI. Major adverse cardiac and cerebral events (MACCE) and bleeding were assessed at 3 months.
Results
At 3 months, major adverse cardiac and cerebral events occurred in 3.1% of the experimental group ( n = 99) vs 2.0% in the control group ( n = 101) (HR: 1.54; 95% CI: 0.26-9.24), clinically relevant bleeding was observed in 4.2% vs 8.9% (HR: 0.46, 95% CI: 0.14-1.48), and clinically relevant non-access site bleeding in 2.0% vs 7.9% (HR: 0.25, 95% CI: 0.05-1.19).
Conclusions
Although no significant difference in ischemic events was observed between the novel concept of ticagrelor monotherapy and DAPT, safety cannot be confirmed given the small number of events. Additionally, there was a tendency for a reduction in clinically relevant non-access site bleeding events.
To improve bleeding outcomes after percutaneous coronary intervention (PCI), a de-escalation strategy to P2Y12 inhibitor monotherapy after a short period of dual antiplatelet therapy (DAPT) has been investigated in both the chronic and acute settings, ,, including in STEMI patients. , This strategy is safe and effective regarding ischemic and bleeding outcomes. As most bleeding complications in the STEMI population occur during the first month, direct omission of aspirin after primary PCI with continuation of a potent P2Y12 inhibitor, the aspirin-free strategy, could further reduce bleeding.
In this randomized pilot study, we aimed to assess the preliminary safety of omitting aspirin directly after primary PCI while continuing ticagrelor monotherapy concerning ischemic events in the first 3 months after STEMI. Additionally, we evaluate the impact of this novel therapeutic strategy on bleeding events.
Methods
Study design and study population
We conducted an open-label, randomized, multicenter pilot study (NCT05986968) in the Netherlands that follows the ethical guidelines of the 1975 Declaration of Helsinki, and has been reviewed and approved by the Medical Ethics Committee. A Data Safety Monitoring Board oversaw the safe conduct of the study. The study design has been previously published. In brief, 200 STEMI patients aged 18 years or older were enrolled and randomized within 24 hours after successful primary PCI to ticagrelor monotherapy or ticagrelor plus aspirin in a 1:1 ratio. Randomization and initiation of the allocated treatment took place before the subsequent oral dose of aspirin after primary PCI.
All patients received a loading dose of aspirin 240 mg and ticagrelor 180 mg before primary PCI according to standard care.
Study outcomes
The primary ischemic endpoint was a composite of major adverse cardiac and cerebral events (MACCE), including myocardial infarction, stent thrombosis, ischemic stroke, and cardiovascular death. Myocardial infarction included spontaneous or periprocedural myocardial infarction according to the universal definition.
The efficacy endpoint included clinical bleeding events, defined as Bleeding Academic Research Consortium (BARC) score grade 2 or higher. We also assessed nonaccess site bleedings as a separate outcome, excluding access-site bleeding which could not be attributed to the randomized treatment strategy. Other endpoints include all-cause death, unplanned revascularization and net adverse clinical events (NACE), which is composed of MACCE, bleeding events and all-cause mortality. Detailed definitions are presented in the Supplementals.
All clinical outcomes were adjudicated in a blinded manner against source documents by a clinical event committee.
Statistical analysis
Because of the exploratory nature of this pilot study, no formal sample size calculation was performed. Based on previous pilot studies with similar designs, a sample of 200 patients was planned. All statistical analyses concerning clinical endpoints were conducted primarily according to the intention-to-treat principles in a blinded manner, with secondary unblinded analyses per protocol. Definitions for the intention-to-treat and per-protocol population can be found in the supplementals. Clinical endpoints were compared between treatment groups using Cox regression analysis. In addition, we reported the absolute risk differences (ARDs) of the clinical endpoints. All statistical analyses were performed with IBM SPSS Statistics (Version 29).
Results
Study population
We randomized 200 patients between July 2023 and December 2024; 99 patients were randomized to the experimental and 101 to the control group ( Figure 1 ). Baseline characteristics are presented in Table 1 . The mean age of the included patients was 64.2 years, and the majority were men (73.5%). The culprit lesion was most frequently the proximal or mid LAD and right coronary artery (RCA). Multivessel disease was present in 42.0% and PCI of bifurcation lesion was performed in 2.5% of patients. Detailed procedural characteristics are shown in Supplementary Table 1.
Flow diagram of enrolment and randomization.
Abbreviation: DAPT, dual antiplatelet therapy.
Table 1
Baseline characteristics
| Total N = 200 | Ticagrelor monotherapy N = 99 | Ticagrelor + Aspirin N = 101 | |
|---|---|---|---|
| Age, years | 64.2 (10.5) | 63.9 (11.1) | 64.45 (9.9) |
| Male sex | 147 (73.5) | 75 (75.8) | 72 (71.3) |
| Body mass index, kg/m 2 | 27.2 (4.2) | 27.3 (4.8) | 27.1 (3.6) |
| Smoking | |||
| Current | 61 (31.4) | 29 (29.9) | 32 (33.0) |
| Former | 48 (24.7) | 25 (25.8) | 23 (23.7) |
| Non | 85 (43.8) | 43 (44.3) | 42 (43.3) |
| Diabetes Mellitus | 25 (12.5) | 10 (10.1) | 15 (14.9) |
| No medication | 3 (1.5) | 0 | 3 (3.0) |
| Oral medication only | 19 (9.5) | 7 (7.1) | 12 (11.9) |
| Insulin dependent | 3 (1.5) | 3 (3.0) | 0 |
| Hypertension | 79 (39.5) | 36 (36.4) | 43 (42.6) |
| Peripheral vascular disease | 2 (1.0) | 1 (1.0) | 1 (1.0) |
| Renal failure | 7 (3.5) | 4 (4.0) | 3 (3.0) |
| Family history of CVD | 77 (43.0) | 35 (39.8) | 42 (46.2) |
| COPD | 12 (6.0) | 5 (5.1) | 7 (6.9) |
| Hypercholesterolemia | 151 (75.9) | 72 (73.5) | 79 (78.2) |
| Heart failure | 4 (2.0) | 3 (3.0) | 1 (1.0) |
| LVEF prior to presentation, % | 50.8 (8.1) | 51.3 (7.9) | 50.3 (8.6) |
| No prior LVEF available | 172 (86.0) | 84 (84.8) | 88 (87.1) |
| Ischemic stroke | 7 (3.5) | 4 (4.0) | 3 (3.0) |
| Previous myocardial infarction | 11 (5.5) | 6 (6.1) | 5 (5.0) |
| Previous PCI | 11 (5.5) | 6 (6.1) | 5 (5.0) |
| Previous bleeding ≤ 1 year before presentation | 3 (1.5) | 1 (1.0) | 2 (2.0) |
| Killip class during admission | |||
| I | 197 (98.5) | 99 (100) | 98 (97.0) |
| > I | 3 (1.5) | 3 (3.0) | |
| Cardiac arrest at admission | 4 (2.0) | 2 (2.0) | 2 (2.0) |
| Lab values | |||
| Hemoglobin (mmol/L) | 8.76 (0.81) | 8.83 (0.81) | 8.87 (0.81) |
| Thrombocytes (10^9/L) | 247.54 (57.12) | 240.55 (54.55) | 254.39 (58.99) |
| Leukocytes (10^9/L) | 10.19 (3.26) | 9.95 (3.04) | 10.43 (3.46) |
| Creatinine (µmol/L) | 80.74 (19.63) | 78.53 (18.20) | 82.90 (20.80) |
| eGFR (mL/min/1.73m 2) | 79.15 (12.88) | 80.53 (12.30) | 77.79 (13.35) |
| Troponin (T and I, times ULN) | 188.42 (40.46-480.77) | 154.77 (40.69-480.77) | 236.82 (36.15-508.46) |
| Access site | |||
| Radial artery | 194 (97.0) | 96 (97.0) | 98 (97.0) |
| Femoral artery | 6 (3.0) | 3 (3.0) | 3 (3.0) |
| Conversion rate | 12 (6.0) | 7 (6.1) | 5 (5.9) |
| Final access site | |||
| Radial artery | 184 (92.0) | 90 (90.9) | 94 (93.1) |
| Femoral artery | 15 (7.5) | 9 (9.1) | 6 (5.9) |
| Brachial artery | 1 (0.5) | 0 | 1 (1.0) |
| PCI of coronary | |||
| Left main | 1 (0.5) | 0 | 1 (1.0) |
| LAD | 84 (42.0) | 43 (43.5) | 41 (40.6) |
| Prox | 37 (18.5) | 15 (15.2) | 22 (21.8) |
| Cx | 26 (13.0) | 9 (9.1) | 17 (16.8) |
| RCA | 97 (48.5) | 49 (49.5) | 48 (47.5) |
| Number of stents implanted | |||
| 1 | 143 (71.5) | 73 (73.7) | 70 (69.3) |
| > 1 | 57 (28.5) | 26 (26.2) | 29 (28.8) |
| Multivessel disease | 84 (42.0) | 35 (35.4) | 49 (48.5) |
| PCI of bifurcation lesion | 5 (2.5) | 3 (3.0) | 2 (2.0) |
| Stent length (mm) of primary PCI (median 25%-75% IQR) | 30.0 (22.0-43.8) | 30.0 (22.0-40.0) | 28.0 (21.0-44.0) |
| TIMI flow pre-PCI | |||
| 0 | 79 (39.5) | 37 (37.4) | 42 (41.6) |
| 1 | 24 (12.0) | 14 (14.1) | 10 (9.9) |
| 2 | 44 (22.0) | 20 (20.2) | 24 (23.8) |
| 3 | 50 (25.0) | 27 (27.3) | 23 (22.8) |
| Not reported | 3 (1.5) | 1 (1.0) | 2 (2.0) |
| TIMI flow post-PCI | |||
| 0 | 0 | 0 | 0 |
| 1 | 1 (0.5) | 1 (1.0) | 0 |
| 2 | 14 (7.0) | 9 (9.1) | 5 (5.0) |
| 3 | 181 (90.5) | 88 (88.9) | 93 (92.1) |
| Not reported | 4 (2.0) | 1 (1.0) | 3 (3.0) |
| Thrombus aspiration performed | 11 (5.5) | 6 (6.1) | 5 (5.0) |
| Post dilatation performed | 144 (72.0) | 73 (73.7) | 71 (70.3) |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
