Objective This study aimed to compare the safety and efficacy of ticagrelor and clopidogrel in reducing major adverse cardiovascular events (MACE) among patients undergoing percutaneous coronary intervention (PCI) for chronic coronary disease. Additionally, secondary endpoints, including adverse events such as major bleeding, minor bleeding, and dyspnea, were assessed to evaluate the overall safety profile of both antiplatelet therapies. Methodology A prospective cohort study was conducted at Kuwait Teaching Hospital, Peshawar, Pakistan, enrolling 300 patients (150 receiving ticagrelor and 150 receiving clopidogrel) from July 2023 to June 2024. Patient selection was based on predefined inclusion and exclusion criteria, ensuring a homogeneous study population. Randomization was not applied, and treatment allocation was guided by physician discretion and clinical indications. Baseline characteristics, primary clinical outcomes (MACE), and secondary endpoints (major bleeding, minor bleeding, and dyspnea) were assessed. Statistical analysis was performed using chi-square tests for categorical variables and independent t-tests for continuous variables, with statistical significance set at p <
0.05. Results Ticagrelor significantly reduced the incidence of stent thrombosis compared to clopidogrel (8 (5.0%) vs. 20 (13.3%)
p = 0.029, χ² = 4.78), indicating a 62.4% relative risk reduction and suggesting superior thrombotic protection in PCI patients. Although revascularization rates were lower with ticagrelor (10 (7.0%) vs. 18 (12.0%)
p = 0.169, χ² = 1.89), the difference was not statistically significant, but the trend suggests a potential clinical benefit in reducing repeat interventions. Major bleeding was higher in ticagrelor users (15 (10.0%) vs. 9 (6.0%)
p = 0.287, χ² = 1.13), aligning with its pharmacodynamic profile and underscoring the need for careful risk stratification in bleeding-prone patients. Dyspnea occurred more frequently with ticagrelor (12 (8.0%) vs. 5 (3.3%)
p = 0.134, χ² = 2.25), likely due to adenosine-related effects, highlighting the importance of monitoring patients with respiratory conditions. Minor bleeding rates were comparable (21 (14.0%) vs. 15 (10.0%)
p = 0.374, χ² = 0.79), indicating no significant difference in less severe bleeding events. Baseline characteristics, including age, BMI, smoking history, diabetes, and hypertension, were statistically similar (p >
0.05), ensuring comparability between the two groups and reinforcing that observed differences in clinical outcomes were treatment-related rather than due to baseline variability. Conclusions Ticagrelor demonstrated superior efficacy in reducing MACE, particularly stent thrombosis, but was associated with higher rates of bleeding and dyspnea. Individualized treatment strategies involve risk stratification, where high ischemic-risk patients benefit most from ticagrelor, while those prone to bleeding may require de-escalation to clopidogrel. Dyspnea and bleeding can impact adherence and quality of life, leading to premature discontinuation. Close monitoring, early symptom recognition, and shared decision-making are essential to optimize therapy, ensuring patients receive maximum benefit while minimizing adverse effects.