Platelets play a crucial role in blood clotting and wound healing. However, excessive platelet aggregation can lead to the formation of blood clots that obstruct blood vessels, causing cardiovascular events like heart attack or stroke. Antiplatelet drugs work by inhibiting platelet aggregation and reducing the risk of blood clots. Over the past few decades, antiplatelets have revolutionized the prevention and treatment of cardiovascular conditions like heart disease and stroke. \

Aspirin

Discovered in the late 1890s, aspirin is the oldest and most commonly used antiplatelet medication. Aspirin works by irreversibly inhibiting the enzyme cyclooxygenase-1 (COX-1) present in platelets. This blocks the formation of thromboxane A2 – a powerful stimulator of platelet aggregation and blood clot formation. Large clinical trials in the 1980s demonstrated aspirin’s efficacy in reducing heart attack risk by 25% and stroke risk by 30% in high-risk patients.

Ever since, low-dose (75-100 mg) aspirin has been the standard first-line therapy for primary and secondary cardiovascular disease prevention. Its anti-clotting effects last for the lifespan of platelets, which is around 10 days. Aspirin is very affordable, and its long-term use comes with minimal risk of side effects like gastrointestinal ulcers if taken correctly. Over-the-counter low-dose aspirin is backed by robust evidence and remains one of the most effective agents for reducing cardiovascular events.

P2Y12 Receptor Inhibitors

While aspirin blocks one pathway of Antiplatelet Drugs activation, P2Y12 receptor inhibitors target a different pathway to achieve stronger and faster platelet inhibition than aspirin alone. Two major classes of P2Y12 inhibitors are thienopyridines and ticagrelor.

Thienopyridines were the first generation P2Y12 inhibitors consisting of drugs like clopidogrel and prasugrel. They work by irreversibly binding to the P2Y12 receptor on platelets. Clopidogrel, launched in the late 1990s, has been widely used following coronary artery stenting and acute coronary syndrome to reduce the risk of thrombosis. However, clopidogrel has some limitations like genetic variability in individual response.

Newer P2Y12 inhibitor ticagrelor overcomes many of clopidogrel’s issues. Studies showed ticagrelor more effectively inhibits platelet aggregation and provided greater reduction in cardiovascular events compared to clopidogrel. Ticagrelor’s onset and offset of action are also faster than thienopyridines. It is now a standard of care for acute coronary syndrome and recovering heart attack patients. P2Y12 inhibitors are prescribed for short durations following a major cardiovascular event or stenting along with long-term aspirin therapy.

Role in Acute Coronary Syndrome

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor forms the cornerstone of treatment in acute coronary syndrome (ACS) conditions like unstable angina and myocardial infarction. During an ACS event, aspirin works immediately to inhibit COX-1 while P2Y12 inhibitors provide added platelet inhibition by blocking the other pathway.

Studies showed dual antiplatelet therapy significantly reduces mortality, recurrent infarction, and ischemic events in ACS patients compared to aspirin alone. International guidelines currently recommend aspirin plus a P2Y12 inhibitor like clopidogrel or ticagrelor for at least 12 months following ACS irrespective of the treatment strategy (medical management/intervention). This dual blockade of platelet aggregation more effectively prevents thrombotic complications during ACS recovery.

Newer Antiplatelets

Several new antiplatelet drugs targeting different pathways are under development to improve efficacy while reducing bleeding risk. Vorapaxar was the first protease-activated receptor 1 (PAR-1) antagonist approved for reducing secondary cardiovascular events. However, it increased bleeding risk and had mixed results. Other promising targets include thromboxane receptors, integrins, and C-type lectin-like receptor-2 (CLEC-2).

Research is also looking at optimizing existing dual therapy. Studies assessed whether replacing aspirin with another drug in select patients may offer advantages. For example, replacing aspirin withclopidogrel alone after stenting may reduce bleeding risk without compromising efficacy. With advancement in drug-eluting stents and techniques, shorter durations of dual antiplatelet therapy are being evaluated compared to the standard 12 months.

Precautions and Bleeding Risks

While antiplatelets significantly lower cardiovascular ischemic risks, they also increase bleeding tendency to some extent. Major bleeding complications from antiplatelets include gastrointestinal hemorrhage and intracranial hemorrhage. Older age, reduced kidney function, previous bleeding history, and concurrent use of other anticoagulants or NSAIDs increase bleeding risks with antiplatelets.

It is crucial to weigh the benefits of preventing future cardiovascular events against the bleeding risk based on individual patient characteristics. Physicians carefully consider antiplatelet choices, dosing, and duration of therapy based on the clinical scenario. Antiplatelets require monitoring for side effects and adherence. Steps like proton pump inhibitor co-prescriptions help mitigate gastrointestinal bleeding risks from long-term aspirin.

The past few decades have seen tremendous advancements in antiplatelet therapy due to the results of large clinical outcome studies. Drugs like aspirin and P2Y12 inhibitors today form the core medical management strategy for preventing cardiovascular diseases. Although newer antiplatelet agents are under research, aspirin continues to demonstrate long-term effectiveness and remain the foundation of antiplatelet therapy. With careful risk-benefit analysis, antiplatelets can significantly reduce morbidity and mortality from heart attacks and strokes on a global scale.

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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it