Stroke Research & Therapy

Description

Antiplatelet therapy is the management of cardiovascular diseases, particularly in preventing and treating thrombotic events such as myocardial infarction, stroke and peripheral arterial disease. This therapeutic approach involves the use of medications that inhibit platelet aggregation, thereby reducing the risk of clot formation. The primary goal of antiplatelet therapy is to maintain blood flow through arteries and veins, minimizing the potential for life-threatening occlusions that can result from thrombi. Platelets play a vital role in hemostasis, the process by which bleeding is stopped following vascular injury. They adhere to the site of injury, become activated, and aggregate to form a plug that helps to seal the wound. While this process is essential for preventing excessive blood loss, it can become pathological when it occurs within the vasculature, leading to the formation of clots that can obstruct blood flow. In conditions such as atherosclerosis, the risk of thrombus formation is significantly increased due to the presence of plaques that can rupture and expose underlying tissue, triggering platelet activation and aggregation. The most commonly used antiplatelet agents include aspirin, clopidogrel, and newer agents such as ticagrelor and prasugrel. Aspirin is perhaps the best-known antiplatelet drug, used for decades due to its effectiveness and relatively low cost. It works by irreversibly inhibiting the enzyme, which is necessary for the production of thromboxane A2, a potent promoter of platelet aggregation. By reducing thromboxane A2 levels, aspirin decreases platelet aggregation and the potential for clot formation.

Antiplatelet therapy

Antiplatelet therapy is also a key component in the secondary prevention of ischemic stroke. Patients who have experienced a Transient Ischemic Attack (TIA) or an ischemic stroke are at high risk for subsequent events. Aspirin, clopidogrel, or a combination of both can be used to reduce the risk of recurrent stroke. The choice between monotherapy and combination therapy depends on the balance between the benefits of enhanced platelet inhibition and the increased risk of bleeding. Peripheral arterial disease is another condition where antiplatelet therapy is beneficial. PAD is characterized by the narrowing of arteries in the limbs, leading to reduced blood flow and an increased risk of claudication, ulceration and gangrene.

Antiplatelet agents help to prevent the progression of the disease and reduce the risk of cardiovascular events in these patients. While antiplatelet therapy offers significant benefits in reducing thrombotic events, it is not without risks. The most notable adverse effect of antiplatelet drugs is bleeding, which can range from minor bruising to life-threatening hemorrhage. The risk of bleeding is influenced by factors such as age, comorbidities and concomitant use of other medications that affect hemostasis. Patients receiving antiplatelet therapy must be closely monitored for signs of bleeding and the risk-benefit ratio should be regularly reassessed. Drug interactions are also an important consideration in antiplatelet therapy. Certain medications, such as nonsteroidal anti-inflammatory drugs, anticoagulants, and selective serotonin reuptake inhibitors can potentiate the bleeding risk when used in conjunction with antiplatelet agents. Physicians must carefully evaluate the patient's medication regimen and make necessary adjustments to minimize the risk of adverse interactions.

Adverse effects

Clopidogrel, another widely used antiplatelet drug, functions through a different mechanism. It is a prodrug that, once metabolized in the liver, irreversibly inhibits the P2Y12 receptor on platelets. This receptor plays a critical role in the activation and aggregation of platelets in response to adenosine diphosphate. By blocking this receptor, clopidogrel reduces the ability of platelets to aggregate and form clots. The effectiveness of clopidogrel can be influenced by genetic variations that affect its metabolism, leading to variability in patient responses. Ticagrelor and prasugrel are newer P2Y12 inhibitors that offer advantages over clopidogrel in certain clinical settings. Ticagrelor, unlike clopidogrel, does not require metabolic activation and provides a more consistent antiplatelet effect. Prasugrel is also a prodrug, but it is more efficiently converted to its active form, leading to more potent inhibition of the P2Y12 receptor. These agents have been shown to reduce the incidence of major adverse cardiovascular events more effectively than clopidogrel in some patient populations, though they may also increase the risk of bleeding. The choice of antiplatelet therapy depends on various factors, including the underlying condition being treated, patient-specific characteristics and the risk of adverse effects. In patients with acute coronary syndromes, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is often recommended to provide robust inhibition of platelet activity during the critical period following a heart attack or placement of a coronary stent. The duration of DAPT can vary, typically ranging from six months to one year, depending on the patient's risk of bleeding and thrombotic events.