Role of Dual Pathway Inhibition in Secondary Prevention of Coronary Artery Disease

Introduction Coronary artery disease (CAD) continues to be a significant global health challenge, contributing to high rates of morbidity and mortality despite advancements in medical care. Dual-pathway inhibition (DPI) represents a major advancement in the secondary prevention of CAD by targeting both platelet aggregation and thrombin generation. Unlike traditional single-pathway antiplatelet therapy (e.g., aspirin or P2Y12 inhibitors), DPI provides a synergistic approach to reduce the residual cardiovascular risk that persists despite optimal medical therapy. Objective To evaluate the efficacy and safety of DPI compared to standard single-pathway antiplatelet therapy in reducing cardiovascular events in patients with CAD. Methodology This prospective observational cohort study was conducted at Shalamar Hospital, Lahore, Pakistan, from September 2023 to August 2024. Data were collected from 147 patients diagnosed with stable CAD or who had experienced a recent acute coronary syndrome. Patients were randomly assigned into two groups: the DPI group and the control group. The DPI group (n=74) received a combination of low-dose rivaroxaban (2.5 mg twice daily) and aspirin (81 mg daily), while the control group (n=73) received standard single-pathway antiplatelet therapy with aspirin (81 mg daily). Results The mean age was similar in both groups, with 56.67 ± 8.01 years in the DPI group and 58.92 ± 9.23 years in the control group (p=0.48). The proportion of male patients was comparable, with 50(68%) in the DPI group and 48(66%) in the control group (p=0.78). Prevalence rates of hypertension [53(72%) vs. 54(74%), p=0.74], diabetes mellitus [31(42%) vs. 29(39%), p=0.69], and previous myocardial infarction (MI) [35(48%) vs. 37(51%), p=0.66] were nearly identical across groups. Similarly, smoking history showed no significant difference, with 26(35%) in the DPI group and 24(33%) in the control group (p=0.81). Cardiovascular deaths were less frequent in the DPI group [2(2.7%)] compared to the control group [5(6.8%)], although this difference did not reach statistical significance (p=0.18). Similarly, the incidence of non-fatal MI [3(4.1%) vs. 7(9.6%), p=0.12] and non-fatal stroke [2(2.7%) vs. 3(4.1%), p=0.63] was lower in the DPI group but not statistically significant. Conclusion It is concluded that DPI is an effective strategy for reducing residual cardiovascular risk in patients with CAD. By combining platelet aggregation and thrombin generation inhibition, DPI significantly lowers the incidence of major adverse cardiovascular events compared to single-pathway antiplatelet therapy.