This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the preliminary efficacy of varenicline tartrate in patients with frequent PVCs complicated by myocardial infarction (MI). The protocol was approved by the institutional review board and ethics committee at each participating center.

Primary Efficacy Endpoint:

1) The percentage change from baseline in the 24-hour mean count of PVCs at Week 6.

Secondary Efficacy Endpoints:

1. The responder rate for PVCs at Weeks 4, 6, and 8. PVC responder: A participant is considered a responder if there is a ≥ 50% reduction from baseline in the 24-hour mean PVC count following treatment with either varenicline or placebo.
2. The incidence of NSVT from randomization through Weeks 4, 6, and 8.
3. The change from baseline in the 24-hour mean count and burden of PVCs at Weeks 4, 6, and 8.
4. The change from baseline in the 24-hour mean episodes and burden of non-sustained ventricular tachycardia (NSVT) at Weeks 4, 6, and 8.
5. The change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score at Week 6.

Pre-specified Safety Endpoints:

Primary Endpoint: The cumulative incidence of the first occurrence of malignant ventricular arrhythmias (time-to-first event), including sustained ventricular tachycardia (SVT), ventricular fibrillation (VF), or ventricular flutter (VFL), from randomization through Weeks 4, 6, and 8.

Study Population:

A total of 116 participants, aged 18-80 years, with frequent PVCs wil be enrolled. Prior to enrollment, participants must have stable cardiac conditions and must have received standard treatment for acute or chronic coronary syndrome as recommended by the relevant guidelines, including sustained-release metoprolol succinate. Following preliminary screening, participants will undergo 72-hour continuous three-lead AECG monitoring (baseline data) to assess the baseline PVC frequency. Eligibility for inclusion will be determined based on the monitoring data. Eligible participants will then be randomized in a 1:1 ratio (Day 0) to either the treatment group (varenicline tartrate tablets) or the placebo group.

Treatment Protocol:

All participants will receive sustained-release metoprolol succinate as part of the standard treatment, in accordance with clinical guidelines. The dose will remain stable throughout the study, unless adjustments are required for patient safety. Other standard treatments recommended by the guidelines, aside from sustained-release metoprolol succinate, will be optimized according to the clinical guidelines throughout the study.

Randomization and Stratification:

A total of 116 participants will be enrolled and randomized to either the treatment or placebo group, with 58 participants in each group. Stratification will be based on left ventricular ejection fraction (LVEF ≥ 50% vs. LVEF < 50%).

Treatment Regimen:

Treatment Group (Varenicline Tartrate 0.5 mg/tablet): Participants will receive the following regimen:

Days 1-3: 0.5 mg once daily. Days 4-42: 0.5 mg twice daily, taken at the same times each day (recommended interval 12 hours ± 2 hours).

Days 43-45: 0.5 mg once daily.

Placebo Group: Participants will receive placebo tablets according to the same regimen as the treatment group:

Days 1-3: 1 tablet once daily. Days 4-42: 1 tablet twice daily, taken at the same times each day (recommended interval 12 hours ± 2 hours).

Days 43-45: 1 tablet once daily. Statistical Analysis General Principles

1. Continuous (quantitative) variables: Summarized with n, mean, standard deviation, median, interquartile range, minimum, and maximum.
2. Categorical (count) variables: Presented as n (%). Unless otherwise specified, percentages will be calculated using the number of participants in the relevant analysis population as the denominator.

Efficacy Analysis

1） Primary endpoint: The between-group difference will be assessed by estimating the mean difference in the percentage reduction from baseline in the 24-hour mean PVC count at Week 6, with 95% confidence intervals (CIs).

Secondary endpoints: Two key secondary efficacy end points will be formally tested using a fixed-sequence (hierarchical) procedure.

Key Secondary End Point 1: The responder rate for PVCs at Week 6. Key Secondary End Point 2: The incidence of NSVT at Week 6. All other secondary efficacy endpoints will be summarized descriptively. Safety Analysis The cumulative incidence of malignant ventricular arrhythmias will be estimated using Kaplan-Meier survival curves, with differences between groups compared using the Cox proportional hazards model (reporting the hazard ratio [HR] and 95% CI). If no events occur in either group or if the number of events is too low, only the number of events and their percentages will be reported.

Inclusion Criteria:

1. Aged between 18 and 80 years old (inclusive).
2. Premature ventricular contractions of ≥1000 times/average 24-hour revealed by screening (72-hour Holter monitoring).
3. Definite diagnosis of myocardial infarction for more than 4 weeks, with NYHA Class I-II.
4. Maintained on Metoprolol Succinate Sustained-release Tablets. (If other types of beta-blocker therapy were being used before screening, they must be replaced with Metoprolol Succinate Sustained-release Tablets.)
5. Understand and comply with the study procedures and methods, and sign the informed consent form.

Exclusion Criteria:

1. Myocardial infarction occurring within 4 weeks.
2. NYHA Class III-IV.
3. Use of amiodarone within 1 month before screening.
4. Use of antiarrhythmic drugs, or traditional Chinese medicine, Chinese patent medicine for arrhythmia other than amiodarone within 1 week prior to screening.
5. Sustained ventricular tachycardia, ventricular flutter, or ventricular fibrillation detected during screening (non-sustained ventricular tachycardia does not need to be excluded).
6. Sick sinus syndrome without pacemaker implantation, II-III degree atrioventricular block, or bundle branch block bilateral.
7. Moderate to severe bronchial asthma or severe chronic obstructive pulmonary disease.
8. Severe renal impairment (eGFR less than 30 mL/min/1.73 m²).
9. Hyperthyroidism.
10. Severe sequelae of stroke.
11. Epilepsy, schizophrenia, or depression.
12. Pregnant or breastfeeding women, or those with a positive blood pregnancy test result before randomization.
13. Combined cancer or other diseases, with an expected life expectancy of less than 1 year.
14. Perioperative period of cardiothoracic surgery (1 week before surgery to 2 weeks after surgery).
15. Severe electrolyte disturbance.
16. Digitalis poisoning.
17. Known hypersensitivity to varenicline tartrate tablets or their excipients.
18. History of smoking and cessation for less than 1 year.
19. Individuals taking varenicline tartrate tablets for smoking cessation.
20. Currently participating in other clinical studies.
21. Other conditions making the subjects unsuitable for enrollment as determined by the investigator.