24 Versus 12-Month Dual Antiplatelet Therapy After Drug-Eluting Stent in Patients With Elevated Lipoprotein(a) Levels: A Prospective, Multicenter, Double-Blind, Placebo-Controlled Randomized Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Elevated Lipoprotein(a) Level
- Sponsor
- China National Center for Cardiovascular Diseases
- Enrollment
- 3300
- Locations
- 1
- Primary Endpoint
- Major adverse cardiovascular and cerebrovascular event (MACCE)
- Status
- Recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
- Main objective Among patients with elevated Lp(a) levels (>30mg/dL) who did not experience cardiovascular events or BARC type 2, 3, or 5 bleeding within 12 months after PCI and DES implantation, was it possible to reduce the primary adverse cardiovascular and cerebrovascular events (a composite endpoint consisting of all-cause death, non-fatal myocardial infarction, and stroke) by extending the duration of DAPT (24 months) compared to the standard duration (12 months)? (Efficacy test)
- Secondary Objectives Key secondary research objective: Among patients with elevated Lp(a) levels (> 30mg/dL) who underwent PCI and received DES implantation within 12 months after the procedure, and who did not experience cardiovascular events or BARC type 2, 3, or 5 bleeding, whether extending the DAPT duration (24 months) compared to the standard DAPT duration (12 months) does not result in an increase in clinical net adverse events (a composite endpoint consisting of all-cause death, non-fatal myocardial infarction, stroke, and BARC type 3 or 5 bleeding) compared to the standard DAPT duration. (Non-inferiority test) Other secondary research objectives: To evaluate the differences in the incidence of the composite endpoint consisting of BARC type 3 or 5 bleeding (the primary safety endpoint) between extending the DAPT duration (24 months) and the standard DAPT duration (12 months); the differences in the incidence of the composite endpoint consisting of cardiovascular death and myocardial infarction; the differences in the incidence of the composite endpoint consisting of all-cause death and myocardial infarction; the differences in the incidence of stent thrombosis; the differences in the incidence of any myocardial infarction; the differences in the incidence of target vessel myocardial infarction; the differences in the incidence of stroke; the differences in the incidence of ischemic stroke; the differences in the incidence of hemorrhagic stroke; the differences in the incidence of cardiovascular death; the differences in the incidence of all-cause death; the differences in the incidence of repeat revascularization; the differences in the incidence of target vessel revascularization; the differences in the incidence of BARC type 2, 3, or 5 bleeding; the differences in the incidence of any bleeding.
Detailed Description
Lp(a) levels play an important role in predicting subsequent ischemic events in patients with established coronary artery disease (CAD), especially those who underwent PCI. However, there are still no approved pharmacologic therapies that specifically target high Lp(a) levels. DAPT consisting of aspirin and a P2Y12 receptor inhibitor represents the cornerstone of pharmacological treatment aimed at preventing thrombotic complications after PCI. Considering that Lp(a) has a prothrombotic effect through its inactive, plasminogen-like protease domain on apo(a), the investigators speculate that prolonged DAPT may have a beneficial effect on reducing future ischemic events in patients with elevated Lp(a) levels after PCI. Some observational studies revealed that DAPT \> 1 year was significantly associated with lower risk of cardiovascular events compared with DAPT ≤ 1 year in patients with elevated Lp(a) levels who were event-free at 1 year after PCI with DES. However, the relative efficacy and safety of prolonged DAPT versus standard DAPT in this high-risk population has never been assessed in randomized controlled trials (RCTs). The DAPT-Lp(a) trial is a multicenter, parallel-group, randomized controlled trial with blinded end-point evaluation. Consecutive patients with Lp(a) levels\>30mg/dL who meet the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to 24-month DAPT group or 12-month DAPT group. The investigators hypothesise that, in patients with Lp(a) levels \>30mg/dL who were event-free at 1 year after PCI with DES, 24-month DAPT is superior to 12-month DAPT with respect to major adverse cardiovascular and cerebrovascular events (primary end point), while it is non-inferior to 12-month DAPT with respect to net adverse clinical events (key secondary end point). The investigators estimated that 3,300 patients would be needed to provide the necessary number of confirmed endpoints to test the study hypothesis. Patients will be followed up at 3, 6, 9, 12 months after randomization. All analyses will be performed according to the intention-to-treat (ITT) principle.
Investigators
Kefei Dou, MD
Professor
China National Center for Cardiovascular Diseases
Eligibility Criteria
Inclusion Criteria
- •Male or nonpregnant female between 18-75 years;
- •Subjects with Lp(a) levels \> 30mg/dL before percutaneous coronary intervention (PCI);
- •PCI procedure with drug-eluting stent (DES) implantation and no cardiovascular events or BARC type 2, 3, or 5 bleeding events occurring within 12 months after the procedure
- •Subjects (or legal guardian) understand the trial requirements and the treatment procedures and provides written informed;
Exclusion Criteria
- •Subjects with Lp(a) \< 30mg/dL or Lp(a) level unavailable before PCI;
- •Subjects who experience adverse cardiovascular events (death, myocardial infarction, stent thrombosis, stroke, repeat coronary revascularization, or Bleeding Academic Research Consortium \[BARC\] type 2, 3 or 5 bleeding) within 1-year after PCI;
- •BARC type 2, 3, or 5 bleeding occurred before PCI
- •Unable to tolerate DAPT therapy or anticoagulant therapy at the same time, long-term use of non-steroidal anti-inflammatory drugs is required Or glucocorticoids;
- •Discontinuation of DAPT for ≥14 days for planned surgical procedures in the next 12 months;
- •Systolic blood pressure \< 90mmHg for \> 30 minutes accompanied by hypoperfusion symptoms or systolic blood pressure ≥ 90mmHg is maintained with mechanical/pharmacologic hemodynamic support;
- •Persistent symptoms of myocardial ischemia;
- •Moderate to severe heart failure (New York Heart Association \[NYHA\] Functional Classification III or IV) or last known left ventricular ejection fraction (LVEF) \< 40%;
- •Severe valvular heart disease, myocarditis or cardiomyopathy;
- •Severe hepatic insufficiency (ALT or AST \> 3 times upper limit of normal, total bilirubin \> 2.5 times upper limit of normal);
Outcomes
Primary Outcomes
Major adverse cardiovascular and cerebrovascular event (MACCE)
Time Frame: 12 months after randomization
The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, non-fatal myocardial infarction or stroke.
BARC type 3 or 5 bleeding
Time Frame: 12 months after randomization
Number of patients with a first occurrence of adjudicated BARC type 3 or 5 bleeding
Secondary Outcomes
- Net adverse clinical event (NACE)(12 months after randomization)
- Cardiovascular death or myocardial infarction(12 months after randomization)
- All-cause death or myocardial infarction(12 months after randomization)
- Stent thrombosis(12 months after randomization)
- Any myocardial infarction(12 months after randomization)
- Target vessel myocardial infarction(12 months after randomization)
- Stroke(12 months after randomization)
- Ischemic stroke(12 months after randomization)
- Hemorrhagic stroke(12 months after randomization)
- Cardiovascular death(12 months after randomization)
- All-cause death(12 months after randomization)
- Repeat revascularization(12 months after randomization)
- Target vessel revascularization(12 months after randomization)
- BARC type 2, 3 or 5 bleeding(12 months after randomization)
- Any bleeding(12 months after randomization)