Clinical trial NCT05785897: STEMI Treated With a Polymer-free Sirolimus-coated Stent and P2Y12 Inhibitor-based SAPT Versus Conventional DAPT
Official title: ST-segment Elevation Myocardial infArction Treated With a Polymer-free Sirolimus-based nanocarrieR Eluting Stent and a P2Y12 Inhibitor-based Aspirin-free Single Antiplatelet Strategy Versus Conventional Dual AntiPlatelet Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: ST Elevation Myocardial Infarction
Keywords: Single antiplatelet therapy
P2Y12 receptor inhibitor
ST-segment elevation myocardial infarction
Polymer-free drug-eluting stent
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Clinical Trials Unit University of Bern
First posted: 2023-03-27
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary percutaneous coronary intervention (PCI) is the preferred revascularization strategy for patients with acute ST-segment elevation myocardial infarction (STEMI). Compared with bare-metal stents (BMS) and early-generation thick-strut polymer-based drug-eluting stents (DES), newer-generation DES with thinner strut stent platforms and durable or biodegradable polymers have been shown to improve long-term safety and efficacy outcomes among patients with STEMI. Accordingly, the use of newer-generation DES over BMS is currently recommended by the most recent guidelines. Vessel healing at the culprit site after DES implantation is however substantially delayed in patients with acute STEMI as compared to those with chronic coronary syndromes and is associated with a long-term risk for recurrent stent-related adverse clinical outcomes. These findings highlight the need for future iterations in modern DES technology to further improve clinical outcomes following PCI in this highest-risk patient subset.

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a potent P2Y12 receptor inhibitor for 12 months after primary PCI for STEMI, unless there are contraindications such as excessive risk of bleeding. A recent meta-analysis of five large-scale randomized clinical trials including a total of 32'145 patients, of whom 4,070 (12.7%) patients were treated for STEMI, indicated that 1-3 months of DAPT followed by P2Y12 inhibitor-based single antiplatelet therapy (SAPT) after second-generation DES implantation in patients with chronic and acute coronary syndromes was associated with lower risk for major bleeding and similar risk for stent thrombosis, all-cause death, myocardial infarction, and stroke compared with conventional DAPT. These findings suggest that a potent P2Y12 inhibitor-based SAPT following a short DAPT course (1-3 months) may represent a preferable treatment option, which is associated with similar ischemic, but lower bleeding risk, for patients undergoing PCI with newer-generation DES compared to standard conventional 12 months DAPT.

The question of whether SAPT using a potent oral P2Y12 inhibitor (ticagrelor or prasugrel) without aspirin (aspirin-free strategy) after primary PCI with a newest-generation thin-strut polymer-free drug-eluting stent is safe and effective compared to a conventional guideline-recommended 6- to 12-month DAPT course among patients with STEMI remains uncertain.

Detailed description: Primary percutaneous coronary intervention (PCI) is the preferred revascularization strategy for patients with acute ST-segment elevation myocardial infarction (STEMI). Compared with bare-metal stents (BMS) and early-generation thick-strut polymer-based drug-eluting stents (DES), newer-generation DES with thinner strut stent platforms and durable or biodegradable polymers have been shown to improve long-term safety and efficacy outcomes among patients with STEMI. Accordingly, the use of newer-generation DES over BMS (class of recommendation I, level of evidence A) is currently recommended by the most recent guidelines of the European Society of Cardiology (ESC) for the management of STEMI. Vessel healing at the culprit site after DES implantation is however substantially delayed in patients with acute STEMI as compared to those with chronic coronary syndromes and is associated with a long-term risk for recurrent stent-related adverse clinical outcomes. These findings highlight the need for future iterations in modern DES technology to further improve clinical outcomes following PCI in this highest-risk patient subset.

Newest-generation DES combining ultrathin-strut cobalt chromium metallic stent platforms with biodegradable polymers were introduced to mitigate chronic inflammation and arterial injury, promote rapid endothelization and improve clinical outcomes following PCI compared with contemporary second-generation durable polymer DES. These features might be particularly important in the enhanced thrombotic and inflammatory environment of acute STEMI and translate into differential clinical outcomes between different DES technologies. In the BIOSTEMI randomized trial, newer-generation biodegradable polymer sirolimus-eluting stents (BP-SES) (Orsiro, Biotronik AG, Switzerland) were found superior to second-generation durable polymer everolimus-eluting stents (DP-EES) (Xience Prime/Expedition, Abbott Vascular, USA) with respect to target lesion failure (TLF) at 1- and 2-year of follow-up among 1,300 patients with acute STEMI undergoing primary PCI, a difference caused by a lower risk for clinically indicated target lesion revascularization. Newest-generation thin-strut polymer-free DES have potential to further mitigate chronic inflammation, promote faster re-endothelialization and reduce DAPT duration, and might represent the future standard-of-care for patients with STEMI undergoing primary PCI. Abluminus DES+ (Concept Medical Inc., India), a novel thin-strut biodegradable polymer sirolimus-eluting stent with a unique Envisolution technology aimed at facilitating early vascular healing. In the en-ABL e-REGISTRY, a large-scale all-comers post-market registry including 2,500 patients, the Abluminus DES+ (Concept Medical Inc., India) showed very low TLF rates (2.2%) among patients with acute myocardial infarction (n=999), suggesting a potential benefit of this newest DES technology in the highest-group of patients with acute coronary syndrome (ACS) with delayed vascular healing. The Abluminus NP (Concept Medical Inc., India) is a novel thin-strut cobalt chromium sirolimus-based nano carrier eluting stent system specially designed to reduce polymer-related inflammation and accelerate vascular healing. In the NANOACTIVE first-in-man study (data not published), the Abluminus NP (Concept Medical Inc., India) has shown promising very low rates of major adverse clinical events among 86 all-comer patients undergoing PCI. However, no dedicated randomized clinical trial to date has evaluated the safety and efficacy of newest-generation thin-strut cobalt chromium polymer-free drug-coated stents for primary PCI in patients with acute STEMI.

2017 ESC guidelines on the management of STEMI recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a potent P2Y12 receptor inhibitor, ticagrelor or prasugrel (or clopidogrel, if ticagrelor or prasugrel are not available or are contraindicated) for 12 months after primary PCI for STEMI, unless there are contraindications such as excessive risk of bleeding (class of recommendation I, level of evidence A). In patients who are at high risk of severe bleeding complications, discontinuation of P2Y12 inhibitor therapy after 6 months may be considered (class of recommendation IIa, level of evidence B). Several randomized clinical trials have investigated alternative antiplatelet therapy strategies for patients with acute STEMI who undergo primary PCI with newer-generation DES. In the DAPT-STEMI randomized, controlled trial, 1,100 STEMI patients who underwent primary PCI with a second-generation DES (Resolute Integrity, Medtronic, USA), and who were event-free at six months on DAPT, were randomized in a 1:1 ratio to aspirin-based single antiplatelet therapy (SAPT) or DAPT for an additional six months. At 18 months, the primary endpoint, a composite of all-cause death, any myocardial infarction, any revascularization, stroke, or Thrombolysis in Myocardial Infarction (TIMI) major bleeding, occurred in 4.8% of patients receiving SAPT and 6.6% of patients receiving DAPT (HR, 0.73; 95% confidence interval (CI), 0.41 to 1.27; p=0.26), meeting the pre-specified study definition for non-inferiority (p for non-inferiority=0.004). In summary, the DAPT-STEMI trial demonstrated that a 6-month DAPT course was non-inferior to standard DAPT for 12 months in patients with event-free STEMI after primary PCI with second-generation DES. However, whether further iterations of DES technology, including thinner-strut stent platforms and biodegradable polymer coatings, may facilitate a shorter DAPT duration with respect of safety (bleeding) and efficacy (ischemic) outcomes has remained uncertain.

A recent meta-analysis of five large-scale randomized clinical trials including a total of 32'145 patients, of whom 4,070 (12.7%) patients were treated for STEMI, indicated that 1-3 months of DAPT followed by P2Y12 inhibitor-based single antiplatelet therapy (SAPT) after second-generation DES implantation in patients with chronic and acute coronary syndromes was associated with lower risk for major bleeding (random-effects model: HR, 0.63; 95%CI, 0.45-0.86) and similar risk for stent thrombosis (random-effects model: HR, 1.19; 95%CI, 0.86-1.65), all-cause death (random-effects model: HR, 0.85; 95%CI, 0.70-1.03), myocardial infarction (random-effects model: HR, 1.05; 95%CI, 0.89-1.23), and stroke (random-effects model: HR, 1.08; 95%CI, 0.68-1.74) compared with conventional DAPT. These findings suggest that a potent P2Y12 inhibitor-based SAPT following a short DAPT course (1-3 months) may represent a preferable treatment option, which is associated with similar ischemic, but lower bleeding risk, for patients undergoing PCI with newer-generation DES compared to standard conventional 12 months DAPT.

The question of whether SAPT using a potent oral P2Y12 inhibitor (ticagrelor or prasugrel) without aspirin (aspirin-free strategy) after primary PCI with a newest-generation thin-strut polymer-free drug-eluting stent is safe and effective compared to a conventional guideline-recommended 6- to 12-month DAPT course among patients with STEMI remains uncertain.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years.
* Subject with acute STEMI planned to undergo primary PCI according to ESC guidelines.
* Subjects with ≥1 acute infarct artery target vessel with ≥1 coronary artery stenosis in a native coronary artery with diameter from 2.25 to 4.0 mm that can be treated with ≥1 coronary stent.
* Subject who underwent successful primary PCI, defined as primary PCI with ≥1 Abluminus NP polymer-free sirolimus-based nanocarrier eluting stent (Concept Medical Inc., India) implantation, and final residual stenosis \<30% by visual estimation or 20% by QCA (quantitative coronary angiography) (28).
* Subject willing to participate and able to understand, read and sign the informed consent document after the primary PCI procedure.

Exclusion Criteria:

* Contraindications to PCI and/or DES implantation.
* Known allergy to aspirin, ticagrelor, prasugrel, or sirolimus.
* Inability to adhere to DAPT for at least 6 months.
* Patient already on DAPT at index presentation due to recent PCI (\<6 months) or ACS (\<12 months).
* Patient on chronic oral anticoagulation at index presentation.
* Patient with mechanical complication of STEMI.
* Patient with acute STEMI due to stent thrombosis.
* Planned non-cardiac surgery that cannot be postponed for at least 6 months.
* Participation or planned participation in another clinical trial, except for observational registries.
* Life expectancy \<1 years.
* Pregnancy.

Primary outcomes:
measure: Rate of major adverse cardiac and cerebrovascular events (MACCE)
timeFrame: 12 months
measure: Rate of BARC class 3 or 5 major bleeding
timeFrame: 12 months
Secondary outcomes:
measure: Rate of any death
timeFrame: 12 months
measure: Rate of any non-fatal myocardial re-infarction
timeFrame: 12 months
measure: Rate of any revascularization
timeFrame: 12 months
measure: Rate of patient-oriented cardiac outcome (POCE)
timeFrame: 12 months
measure: Rate of target lesion failure (TLF)
timeFrame: 12 months
measure: Rate of target vessel failure (TVF)
timeFrame: 12 months
measure: Rate of fefinite or probable stent thrombosis
timeFrame: 12 months
measure: Rate of definite stent thrombosis
timeFrame: 12 months
measure: Rate of BARC ≥2 major bleeding
timeFrame: 12 months
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
Study officials:
affiliation: University Hospital, Geneva
name: Juan F. Iglesias, MD
role: PRINCIPAL_INVESTIGATOR
References: