Comparative Efficacy and Safety of Novel Antiplatelets and Standard Therapy in Patients With Coronary Artery Disease

Abstract

Coronary artery disease (CAD) is a significant health concern that has affected approximately 110 million people worldwide. CAD is defined as persistent narrowing of the coronary arteries as a result of atherosclerotic plaque build-up. Acute coronary syndrome (ACS), which encompasses ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, often results from plaque ruptures. Platelets are crucial for atherogenesis, vascular inflammation, and oxidative stress. Antiplatelet therapy aimed at reducing thrombotic events is vital for ACS treatment. Clinical guidelines advise the use of dual antiplatelet therapy (DAPT) that combines aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) in ACS patients undergoing percutaneous intervention (PCI). This study aimed to assess comprehensively the effectiveness and safety of ticagrelor and prasugrel in comparison to clopidogrel in patients with ACS. An extensive literature search was conducted using PubMed, PubMed Central (PMC), ScienceDirect, and EBSCO databases. The search revealed studies that compared ticagrelor and prasugrel to clopidogrel in ACS patients, and we selected these studies based on specific inclusion and exclusion criteria, which included observational studies, clinical trials, literature reviews, and meta-analyses involving adult ACS patients treated with ticagrelor, prasugrel, or clopidogrel. The efficacy outcomes were defined as major adverse cardiovascular events (MACE) and thrombotic events, whereas the safety outcomes were measured by major and minor bleeding and hemorrhagic stroke. After a rigorous quality assessment to minimize bias, 23 studies were selected for analysis. The findings indicated that novel antiplatelets reduced MACE but increased bleeding complications, with ticagrelor consistently associated with dyspnea. In conclusion, novel P2Y12 inhibitors provide cardiovascular benefits but require careful patient selection and monitoring due to gastrointestinal bleeding (GIB) risks. Future research should standardize bleeding definitions and assess long-term outcomes. Ticagrelor and prasugrel may be more effective and safer than clopidogrel in ACS patients. Given the high risk of GIB, especially among older individuals or those with a past stroke, it is advisable to suggest a lower prasugrel dose without raising the bleeding rates. Since fewer patients use the novel antiplatelet regimen compared to clopidogrel, future clinical trials should include a broader patient population and compare these regimens.

Keywords: acute coronary syndrome (acs); clopidogrel; coronary artery disease (cad); dual-antiplatelet therapy (dapt); gastrointestinal bleeding (gib); p2y12 antagonists; prasugrel; safety and efficacy; systematic review; ticagrelor.

Figure 1. Atherosclerotic plaque and platelet interplay.

The image demonstrates the involvement of platelets in atherosclerotic plaque formation and the action of key antiplatelet drugs. The image is created by the authors of this study using BioRender.com.

Figure 2. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart

NOS: Newcastle-Ottawa Scale; SANRA-2: Scale for the Assessment of Narrative Review Articles 2

Figure 3. Biotransformation and mechanism of action of clopidogrel, ticagrelor, and prasugrel.

Clopidogrel undergoes extensive CYP-mediated oxidation and a very small quantity reaches into final circulation. Ticagrelor is rapidly absorbed in the intestine and does not require any biotransformation. The image is created by the authors of this study using BioRender.com.

Figure 4. Careful balance is crucial when considering the benefits of novel P2Y12 inhibitors compared to clopidogrel.

The image is created by the author (Ravindra Reddy Gangavarapu) of this study.