Highlights
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Early oral anticoagulation monotherapy after PCI with a bioabsorbable-polymer stent is feasible.
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One-month dual therapy followed by oral anticoagulation alone may reduce bleeding without increasing ischemic risk.
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Findings support randomized trials of early oral anticoagulation-only strategies after PCI.
Abstract
Background
In high-bleeding-risk (HBR) patients undergoing percutaneous coronary intervention (PCI), shortening dual antiplatelet therapy (DAPT) is essential, but the optimal approach in those requiring oral anticoagulation (OAC) is uncertain. We evaluated a 1-month dual antithrombotic regimen in HBR patients with and without OAC indication in a prespecified sub-analysis of the POEM trial.
Method
POEM enrolled HBR patients treated with a bioresorbable polymer everolimus-eluting stent. Patients were stratified by OAC indication: the non-OAC group ( n = 281) received 1-month DAPT followed by single antiplatelet therapy; the OAC group ( n = 158) received 1-month OAC plus a P2Y12 inhibitor followed by OAC monotherapy. Time-to-event outcomes were analyzed using the log-rank test, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression models. The primary analysis was conducted according to the intention-to-treat principle. A per-protocol analysis, excluding patients with DAPT duration >1 month, was performed as a sensitivity analysis.
Results
At 1 year, the primary endpoint, a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis, occurred in 6.1% of the non-OAC group versus 2.6% of the OAC group (HR 0.41, 95% CI 0.14–1.22; P =.097). Secondary ischemic outcomes were similar. BARC type 3–5 bleeding was infrequent (2.6% vs 1.3%; P =.369). The per-protocol analysis showed consistent results.
Conclusions
In HBR patients after PCI, transition to OAC monotherapy at 1 month was associated with low ischemic and bleeding risks, comparable to single antiplatelet therapy. These findings support early OAC monotherapy as a feasible strategy warranting randomized investigation.
Trial Registration
EudraCT Number: 2016‐004510‐99; clinicaltrials.gov : NCT03112707.
Graphical abstract
Primary endpoint was a composite of cardiac death, MI, or definite/probable stent thrombosis. HBR, High Bleeding risk; OAC, Oral anticoagulation; LAD, left anterior descending; LM, Left Main; P2Y12i, P2Y12 inhibitors; HR, Hazard Ratio; ITT, Intention to treat.
Background
Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents effectively reduces stent-related ischemic events, though its prolongation increases bleeding risk. This is particularly relevant in patients at high bleeding risk (HBR), where bleeding events carry a prognostic impact comparable to myocardial infarction or stroke. ,
Recent randomized trials have demonstrated that abbreviated DAPT followed by single antiplatelet therapy is a safe and effective option in HBR patients undergoing PCI. ,,, However, the management of these patients is complicated by the need for long-term oral anticoagulation (OAC). While DAPT– combining a P2Y12 inhibitor and aspirin– is crucial for preventing stent thrombosis and myocardial infarction (MI) post-PCI, its prolonged use, especially as part of triple antithrombotic therapy with an OAC, significantly elevates bleeding risk. ,
Current evidence strongly supports the early discontinuation of aspirin in favor of dual antithrombotic therapy (DAT), which combines a direct oral anticoagulant (DOAC) with a single P2Y12 inhibitor, preferably clopidogrel. ,,,,,, This approach has been shown to reduce major bleeding without a significant compromise in ischemic protection. Accordingly, current guidelines recommend limiting triple therapy to the shortest feasible duration, typically 1 week to 1 month, followed by DAT for up to 12 months. ,
The POEM trial uniquely tested an alternative regimen: in OAC patients undergoing PCI, antiplatelet therapy was discontinued after 1 month, with continuation of OAC alone. While the primary publication reported the overall safety of a 1-month antithrombotic strategy, it remained unknown whether outcomes differed between patients with and without OAC indication. In this prespecified sub-analysis of the POEM trial, we stratified patients by OAC indication: those without OAC received 1 month of DAPT followed by aspirin monotherapy, whereas those requiring OAC received 1 month of DAT followed by OAC monotherapy. The objective was to assess the safety and efficacy of these 2 abbreviated strategies in complementary high-risk populations.
Methods
Study population
This study is a prespecified subgroup analysis of the POEM trial (EudraCT Number: 2016‐004510‐99; clinicaltrials.gov : NCT03112707 ), the design and primary results of which have been published previously. ,,, In brief, the trial enrolled patients at HBR who underwent PCI with a BP‐EES, specifically the Synergy stent (Boston Scientific Corporation, Marlborough, MA), featuring a thin‐strut (74–81 μm) platinum‐chromium platform with an abluminal ultrathin (4 μm) poly (DL‐lactide‐co‐glycolide) coating that fully resorbs after drug elution. HBR was defined by at least one of the following criteria: age ≥75 years; need for chronic OAC; anemia (hemoglobin < 11 g/dL); recent blood transfusion (within 4 weeks); thrombocytopenia (platelets <100,000/mL); prior bleeding requiring hospitalization (within 12 months); prior stroke (within 12 months); history of intracerebral hemorrhage; severe chronic liver disease; chronic kidney disease (creatinine clearance <40 mL/min); active cancer (within 3 years); planned major noncardiac surgery (within 12 months); planned long-term use of glucocorticoids or NSAIDs (>30 days); or expected nonadherence to DAPT. The only exclusion criterion was cardiogenic shock. All clinical presentations were eligible, including unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and STEMI, as defined by contemporary international guidelines. High-sensitivity troponin assays were routinely used to differentiate unstable angina from NSTEMI.
All participants were prescribed a 1‐month course of dual-agent antithrombotic therapy. Patients not requiring OAC received DAPT (aspirin plus a P2Y12 inhibitor), followed by aspirin monotherapy. Patients requiring OAC received DAT (OAC plus a P2Y12 inhibitor), followed by OAC monotherapy thereafter. The 1‐year primary endpoint of the main trial—a composite of cardiac death, MI, or definite/probable stent thrombosis—met its noninferiority objective.
For this sub-analysis, patients were stratified into 2 groups based on the indication for OAC at baseline: the non-OAC group (receiving 1-month DAPT) vs the OAC group (receiving 1-month DAT).
Study endpoints and definitions
The primary endpoint for this analysis was the composite of cardiac death, MI, or definite/probable stent thrombosis at 12 months, similarly to the parental trial. Secondary endpoints included the individual components of the primary endpoint, all‐cause death, target‐lesion revascularization (TLR), target‐vessel revascularization (TVR), cerebrovascular events, BARC (Bleeding Academic Research Consortium) type 3–5 bleeding, target‐lesion failure (TLF, a composite of cardiac death, target-vessel MI, or TLR), and net adverse clinical events (NACE, a composite of all-cause death, MI, definite/probable stent thrombosis, or BARC type 3–5 bleeding).
Statistical analysis
The primary analysis was conducted according to the intention-to-treat principle. Patients in the OAC group were compared to those in the non-OAC group. Categorical variables were reported as counts and percentages and compared using the χ² test or Fisher’s exact test. Continuous variables were presented as mean ± standard deviation (SD) or median with interquartile range (IQR) and compared using the Student’s t-test or the Mann–Whitney U test, as appropriate. Time-to-event outcomes were analyzed using the log-rank test, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression models. A per-protocol analysis, excluding patients with DAPT duration >1 month, was performed as a sensitivity analysis. All analyses were conducted using STATA version 14 (Stata Corp., College Station, TX).
Results
Patient and procedural characteristics
Among the patients enrolled in the POEM trial, 281 (63.4%) did not require OAC, and 158 (35.6%) did. Atrial fibrillation was the indication to OAC in 81.6% of cases. Baseline characteristics were generally well-balanced between the 2 groups ( Table 1 ), with some exceptions. The non-OAC group had a higher prevalence of insulin-treated diabetes mellitus (18.2% vs 7.6%, P =.003) and chronic kidney disease (19.3% vs 10.1%, P =.008). Conversely, patients in the OAC group had a higher body weight (78.6 ± 13.6 kg vs 74.9 ± 14.1 kg, P =.006) and higher baseline bleeding risk scores (median HAS-BLED: 3 vs 2, P <.001; median PARIS Bleeding: 6 vs 5, P <.001). Stable coronary artery disease was the most common clinical presentation in both groups.
Table 1
Baseline characteristics
| Non OAC ( N = 281) | OAC ( N = 158) | P | |
|---|---|---|---|
| Demographics | |||
| Age, year | 74.2 ± 9.7 | 75.7 ± 8.2 | .100 |
| Female sex | 85 (30.2) | 42 (26.6) | .416 |
| White race | 273 (97.5) | 157 (100) | .136 |
| Weight, Kg | 74.9 ± 14.1 | 78.6 ± 13.6 | .006 |
| BMI, kg/m 2 | 26.3 ± 4.0 | 27.3 ± 4.1 | .016 |
| Comorbidities and cardiac history | |||
| Diabetes mellitus | 113 (41.1) | 50 (31.8) | .057 |
| Diabetes mellitus on insulin therapy | 50 (18.2) | 12 (7.6) | .003 |
| Hypertension | 240 (87.0) | 142 (90.0) | .368 |
| Dyslipidemia | 189 (69.2) | 105 (67.3) | .680 |
| Smoking (current or former) | 112 (45.2) | 62 (44.3) | .644 |
| Family history of CAD | 72 (31.6) | 30 (24.2) | .145 |
| Chronic kidney disease | 56 (19.3) | 16 (10.1) | .008 |
| Prior PCI | 86 (31.4) | 56 (35.7) | .363 |
| Prior CABG | 23 (8.4) | 15 (9.5) | .674 |
| LVEF <50% | 84 (38.4) | 57 (44.5) | .258 |
| Prior stroke | 14 (5.1) | 10 (6.4) | .583 |
| Peripheral artery disease | 40 (14.8) | 20 (13.2) | .659 |
| HAS-BLED Score | 2 (2-3) | 3 (2-3) | <.001 |
| PARIS Bleeding Score | 5 (4-7) | 6 (5-8) | .001 |
| Clinical presentation | .296 | ||
| Stable angina | 115 (41.2) | 58 (37.2) | |
| Unstable angina | 44 (15.8) | 23 (14.7) | |
| NSTEMI | 52 (18.6) | 27 (17.3) | |
| STEMI | 22 (7.9) | 9 (5.8) | |
| Silent ischemia | 46 (16.5) | 39 (25.0) | |
| NYHA Class | .326 | ||
| Class I | 105 (56.1) | 43 (48.3) | |
| Class II | 61 (32.6) | 29 (32.6) | |
| Class III | 19 (10.2) | 15 (16.8) | |
| Class IV | 2 (1.1) | 2 (2.2) | |
| Laboratory tests | |||
| Hemoglobin, g/dL | 12.7 ± 2.0 | 13.0 ± 2.1 | .272 |
| Platelet count, ^10 3/mm 3 | 211±74 | 217±71 | .532 |
| Creatinine, mg/dL | .897 | ||
| Creatinine clearance, ml/min | 64±29 | 64±23 | .931 |
| Glycated hemoglobin, % | 6.2 ± 1.1 | 6.2 ± 1.6 | .640 |
| Glucose, mg/dL | 126±56 | 119±38 | .993 |
| Total cholesterol, mg/dL | 158±40 | 158±41 | .878 |
| LDL, mg/dL | 92±37 | 97±35 | .445 |
BMI, body mass index; CABG, Coronary Artery Bypass Grafting; CAD, coronary artery disease; LDL, low-density lipoproteins; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; NSTEMI, non-ST segment elevation myocardial infarction; STEMI, ST segment elevation myocardial infarction; chronic kidney disease was defined as creatinine clearance <40 ml/min.
Procedural characteristics are summarized in Table 2 . The 2 groups were similar, although radial artery access was used more frequently in the non-OAC group (86.5% vs 77.2%, P =.025), and there were some differences in target vessel distribution.
Table 2
Procedural characteristics
|
Non-OAC
( N = 281 patients) * ( N = 387 lesions) † |
OAC
( N = 158 patients) * ( N = 210 lesions) † |
P | |
|---|---|---|---|
| Access site * | .025 | ||
| Femoral | 38 (13.5) | 35 (22.1) | |
| Radial | 243 (86.5) | 122 (77.2) | |
| Brachial | 0 (0) | 1 (0.6) | |
| Target vessel † | .030 | ||
| LM | 13 (3.4) | 15 (7.1) | |
| LAD | 168 (43.4) | 103 (49.0) | |
| LCX | 98 (25.3) | 54 (25.7) | |
| RCA | 103 (26.6) | 37 (17.6) | |
| Graft | 5 (1.3) | 1 (0.5) | |
| In stent restenosis † | 35 (9.0) | 23 (10.9) | .452 |
| Thrombus † | 21 (5.4) | 9 (4.3) | .695 |
| In stent thrombosis * | 2 (0.7) | 3 (1.9) | .356 |
| Bifurcations † | 62 (16.0) | 47 (22.4) | .055 |
| AHA/ACC B2/C lesions † | 191 (49.3) | 104 (49.5) | .968 |
| Total Synergy stent implanted * | 1.6 ± 0.9 | 1.8 ± 1.3 | .162 |
| Mean stent diameter, mm | 3.0 ± 0.5 | 3.0 ± 0.5 | .346 |
| Total stent length, mm * | 41.4 ± 27.3 | 42.5 ± 30.2 | .944 |
| IVUS/OCT † | 12 (3.1) | 8 (3.8) | .641 |
| Rotablation † | 17 (4.4) | 14 (6.7) | .249 |
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