Inclusion Criteria:
1. Willing and able to give written informed consent for participation in the trial.
2. Male or female participants age ≥50 years. For male participants, those who are potent and sexually active with a female partner of childbearing potential must agree to use effective male contraception during the trial, defined as either vasectomy with a confirmed negative semen analysis or use of a male condom. In addition, the female partner must use appropriate contraception during the trial and for at least 6 months after the participant's last dose of trial treatment. Female participants must be post-menopausal (≥12 months spontaneous amenorrhea without other cause, or FSH thresholds if needed) or permanently sterile for at least 6 months prior to dosing (eg, bilateral oophorectomy, total hysterectomy, bilateral tubal ligation) or use highly effective contraception from Screening, for the duration of trial treatment and for the specified post treatment period (see Appendix 3).
* Age ≥55 years with ≥12 months of spontaneous amenorrhea, or
* Age \<55 years with ≥12 months of spontaneous amenorrhea and FSH in the postmenopausal range, or surgical menopause (bilateral oophorectomy, with or without hysterectomy) documented in the medical history.
3. Stable, documented atherosclerotic CAD (ESC Chronic Coronary Syndromes): Asymptomatic or symptomatic CCS with objective documentation of atherosclerotic/obstructive CAD, and clinically stable, defined as:
* ≥6 months since the initial documented diagnosis of CAD, and
* if prior PCI or ACS: ≥6 months since the most recent event, and
* if prior CABG: ≥12 months since the most recent CABG, and
Objective documentation must include ≥1 of the following:
* History of ACS (unstable angina, NSTEMI, STEMI) attributable to atherosclerotic CAD, or
* Prior coronary revascularization (PCI or CABG), or
* Obstructive CAD on imaging: ≥50% luminal stenosis in ≥1 epicardial coronary artery on invasive coronary angiography or computed tomography coronary angiography.
4. Ongoing treatment with a low dose aspirin 75-100 mg for at least 30 days prior randomization
5. Stable standard of care treatment (ie, ongoing since at least 30 days prior to randomization) that is intended to continue unchanged during the trial
Exclusion Criteria:
1. Women who are pregnant, currently breastfeeding, or planning pregnancy during the trial or within the defined post treatment period are not eligible.
2. Ischemia with non-obstructive coronary arteries/ Angina with non-obstructive coronary arteries /vasospastic/microvascular angina or suspected CAD without objective evidence of obstructive atherosclerotic CAD at screening.
3. Any clinical suspicion of acute coronary syndrome or unstable angina at randomization according to ESC criteria:
* Rest angina (pain of characteristic nature and location occurring at rest and for prolonged periods \>20 min).
* New-onset angina (recent \[≤2 months\] onset of moderate-to-severe angina, Canadian Cardiovascular Society grade II or III).
* Crescendo angina (previous stable angina that progressively increases in severity and intensity and occurs at a lower threshold over a short period of time).
4. Presence of ≥2 minor or ≥1 major bleeding risk criterion at screening as defined below:
Minor Criteria
* Age ≥75 years
* Hemoglobin 11-12.9 g/dL for men and 11-11.9 g/dL for women
* One event of spontaneous bleeding requiring hospitalization or transfusion ≥6 months ago
* Long-term use of oral NSAIDs or corticosteroids
* Ischemic stroke \>6 months ago Major Criteria
* Ongoing indication (including but not limited to atrial fibrillation, venous thromboembolism, mechanical cardiac valves) for or anticipated use of long-term oral anticoagulation (DOAC, VKA or LMWH or other similar anticoagulants)
* Severe or end-stage chronic kidney disease (estimated glomerular filtration rate \<30 mL/min)
* Hemoglobin \<11 g/dL
* Spontaneous bleeding requiring hospitalization or transfusion in the past 6 months or at any time if recurrent (≥2 occasions)
* Platelet count \<100 × 109/L.
* Chronic bleeding diathesis or family history thereof.
* Liver cirrhosis with portal hypertension
* Active malignancy - (excluding nonmelanoma skin cancer) within the past 12 months
* Previous spontaneous intracranial hemorrhage (at any time)
* Previous traumatic intracranial hemorrhage within the past 12 months
* Presence of a brain arterio-venous malformation
* Ischemic stroke within the past 6 months.
5. Use of DAPT at the time of randomization.
6. Major surgery during the last 30 days before screening or planned major surgery or intervention within the trial period.
7. New York Heart Association class III-IV heart failure at screening or randomization, hospitalization for exacerbation of chronic heart failure within the previous 12 months, or other indices of unstable heart failure.
8. Documented left ventricular ejection fraction \<30% at screening, based on available prior or current assessment.
9. Clinically significant arrhythmia associated with hemodynamic instability or impaired organ perfusion, unless adequately controlled with stable therapeutic management for at least 3 months prior to Screening
10. Liver chemistry abnormalities at Screening (central laboratory reference ranges): exclusion if any of the following apply:
1. ALT and/or AST \> 1.5 × ULN; and/or
2. Total bilirubin \> 1.5 × ULN (participants with documented Gilbert's syndrome: exclude only if total bilirubin \> 3.0 × ULN and/or direct bilirubin \> 1.5 × ULN); and/or
3. Gamma-glutamyl transferase (gamma-glutamyl transpeptidase ) \> 2.0 × ULN
11. Expected survival time \< 1 year due to non-cardiac disorders.
12. Clinically significant acute illness within 7 days before the first dose of trial drug.
13. Donation of \> 300 mL of blood within 56 days before the first dose of trial drug.
14. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
15. History of severe intolerance to subcutaneous injection (minor reactions such as localized swelling or redness are permitted).
16. Receipt of an investigational product within 30 days or 5 half-lives (whichever is longer) before the first dose of the trial drug, or current participation in the follow-up phase of another clinical trial. Any prior use of advanced therapies (ASO/siRNA/gene therapy/cell therapy) should be evaluated and judged by the Investigator.
17. Any underlying disease, or surgical or medical condition that, in the opinion of the Investigator, might interfere with the participant's ability to comply with the protocol or with the interpretation of the clinical trial results.
18. Evidence of active HBV, HCV, or HIV infection at screening, defined as: HBsAg positive; anti HCV positive with clinical/laboratory evidence of active or chronic hepatitis as assessed by the Investigator (participants with documented resolved/treated HCV and no evidence of active disease may be eligible); or HIV-1/2 Ag/Ab reactive with confirmatory test positive.
