Introduction
Coronary artery disease (CAD) is a prominent cause of mortality today. Coronary artery disease is a significant health concern in industrialized and developing nations. Coronary artery disease has several underlying causes, including non-modifiable and modifiable etiologic factors. According to one study, CAD accounted for 32.7 percent of cardiovascular illnesses and 2.2 percent of the world's overall disease burden. Regardless of gender, it has been found that the incidence of CAD increases with age.
What Is Coronary Artery Disease?
The formation of atherosclerotic plaque is a defining feature of the pathophysiology of CAD. A buildup of fatty substances called plaque causes the artery lumen to constrict and obstruct blood flow to the cardiac tissues and muscles. If no more injury to the endothelium (inner layer of the blood vessel) occurs, this plaque may eventually stabilize or increase. As time passes, the lesion may become hemodynamically substantial enough for angina symptoms to develop if insufficient blood reaches the cardiac tissue during elevated demand. An electrocardiogram (EKG), echo, chest X-ray (CXR), stress tests, cardiac catheterization, and blood testing are some of the significant modalities used to assess for coronary artery disease.
Acute coronary syndrome (ACS) or stable ischemic heart disease (SIHD) are two possible manifestations of CAD. The former is more acutely present, while the latter is more chronically prevalent. Both non-pharmacologic and pharmaceutical therapies are used to treat SIHD. Quitting smoking, exercising regularly, losing weight, maintaining excellent control of diabetes and hypertension, and maintaining a nutritious diet are all lifestyle changes or non-pharmacologic interventions. Cardioprotective and angiotensin-blocking drugs are examples of pharmacologic treatments.
ACS is characterized by abrupt onset, substernal chest discomfort, or pressure frequently radiating to the left arm and neck. It may also be accompanied by dyspnea, palpitations, fainting, syncope, cardiac arrest, or newly developed congestive heart failure. All patients with ACS require an immediate EKG to check for STEMI (ST-elevation myocardial infarction), routinely performed pre-hospital by an emergency medical services team. Percutaneous coronary intervention (PCI) is necessary immediately if STEMI is present. At the time of presentation, all patients should receive a total dosage of sublingual aspirin (324 mg). Depending on the patient profile, P2Y12 inhibitors (prasugrel, ticagrelor, or prasugrel) should be begun. Patients with moderate to high TIMI (Thrombolysis in Myocardial Infarction) values (>2) are advised to start early invasive treatment for NSTEMI (Non-ST-Elevation Myocardial Infarction) within 24 hours.
What Is Percutaneous Coronary Intervention?
A non-surgical, invasive therapy called percutaneous coronary intervention (PCI) aims to treat coronary artery constriction or blockage and enhance blood flow to ischemic tissue. This is often accomplished using various techniques. The most popular is inflating the narrow region or inserting a stent to keep the artery open. In this non-surgical procedure, PCI, formerly known as angioplasty with stent, a small device called a stent, is inserted into an atherosclerotic blood artery that has constricted due to plaque development in the heart. By improving blood flow, PCI reduces angina, which makes the individual feel better and increases their capacity for activity. PCI is often planned. Blood vessel access for catheter insertion can be achieved through either the arm or the groin area. Fluoroscopy, a form of X-ray imaging, is employed to guide the placement of a catheter into the heart at the site of coronary artery constriction. A balloon tip coated with a stent is inflated once the tip is positioned. The stent is expanded, and the balloon tip compresses the plaque. Once the plaque has been crushed and the stent is in position, the balloon is inflated and removed. By keeping the artery open, the stent remains in place. Over the past few years, percutaneous coronary intervention has seen widespread usage. 80% of PCI procedures use stents. The complications of atherosclerosis, such as short-term mortality, myocardial infarction, and target vessel revascularization, have all significantly decreased in PCI patients over the past 20 years.
What Is P2Y12 Inhibitor Monotherapy?
P2Y12 receptor is a platelet ADP (Adenosine diphosphate) receptor; that is, it causes platelet aggregation and platelet shape change. A platelet ADP receptor, the P2Y12 receptor is also a G-protein-coupled receptor (GPCR) (mediator of cellular responses) connected to the inhibitory G protein Gi2. Adenylyl cyclase (catalyzes ATP (adenosine triphosphate) into intracellular messenger) is inhibited upon activation of platelet P2Y12 receptors by ADP, and additional downstream events such as activation of phosphatidylinositol-3-kinase and inhibition of Ras GTPase-activating protein 3 (RASA3) are also triggered, promoting GTPase Rap1b activity and integrin activation, ultimately controlling platelet aggregation. Platelet aggregation is eventually amplified and stabilized as a result of these interactions. P2Y12 inhibitors have strong antiplatelet effects by inhibiting P2Y12 receptors and ADP-induced platelet activation.
A unique therapeutic approach known as 'P2Y12 inhibitor monotherapy' is increasingly getting considered among the medical fraternity as it reduces the time needed for DAPT (Dual antiplatelet therapy, combination of aspirin and P2Y12) to one to three months and replaces aspirin with a P2Y12 inhibitor. The scientific rationale for this treatment plan is using a more potent antiplatelet drug to prevent repeat ischemia episodes and avoid potential gastrointestinal side effects primarily caused by aspirin. The results of almost all the extensive randomized controlled trials that examined this unique strategy were positive.
What Is the Significance of P2Y12 Inhibitor Monotherapy in Patients Undergoing Percutaneous Coronary Intervention?
The term "dual antiplatelet therapy" (DAPT) refers to the use of aspirin together with an oral P2Y12 receptor inhibitor. Although DAPT has a proven track record of success, it is also associated with an unavoidably elevated risk of bleeding linked to unfavorable consequences, including higher mortality. The most often given oral P2Y12 inhibitor is clopidogrel. The only P2Y12 inhibitor indicated by the guidelines for use after PCI in individuals with chronic coronary syndromes (CCS) is clopidogrel. However, because clopidogrel is a prodrug that must undergo hepatic (liver) metabolism to become active, the ultimate effects are highly variable. It's significant to note that individuals who continue to have high platelet reactivity (HPR) despite taking clopidogrel have a higher risk of developing thrombotic events following PCI. Increased platelet reactivity is a risk factor for developing stent thrombosis. Acute coronary syndrome (ACS) individuals are more likely to create HPR.
A lot of research has been seeking to reduce bleeding risk while maintaining effectiveness and on the approach of stopping aspirin after a brief DAPT phase and continuing P2Y12 inhibitor treatment. Therefore, the standard therapy for ACS patients is choosing the newer generation P2Y12 inhibitors prasugrel and ticagrelor over clopidogrel due to their solid and consistent antiplatelet effects.
According to the 2021 American College of Cardiology (ACC), American Heart Association (AHA), and Society for Cardiovascular Angiography and Interventions (SCAI) guidelines for coronary artery revascularization, shorter duration DAPT (1-3 months) is reasonable in some patients undergoing PCI, with a transition to P2Y12 inhibitor monotherapy occurring later to lower the risk of bleeding events.
Conclusion
A growing body of research recommends stopping aspirin and continuing P2Y12 inhibitor monotherapy over the long term to shorten the length of DAPT. Clinical recommendations in Europe and the USA currently support discontinuing aspirin rather than the P2Y12 inhibitor when switching from dual antiplatelet medication to single antiplatelet therapy. After percutaneous coronary intervention (PCI), P2Y12 inhibitor monotherapy (P2Y12) is becoming a viable option for dual antiplatelet treatment.
