Pharmacology of Antiplatelet Drugs

Introduction/Overview

Antiplatelet drugs constitute a cornerstone of pharmacotherapy for the prevention and management of atherothrombotic events. These agents function by inhibiting platelet activation, adhesion, and aggregation, thereby impeding the formation of occlusive thrombi within the arterial circulation. The clinical significance of these drugs is underscored by their central role in reducing morbidity and mortality associated with acute coronary syndromes, ischemic stroke, and peripheral arterial disease. The evolution of antiplatelet therapy reflects an increasing understanding of platelet biology and the complex interplay of signaling pathways involved in thrombus formation.

The therapeutic rationale for antiplatelet intervention is predicated on the pathophysiology of arterial thrombosis, where platelet activation is initiated by endothelial injury and exposure of subendothelial matrix proteins. Unchecked platelet aggregation can lead to vascular occlusion, resulting in tissue ischemia and infarction. Consequently, antiplatelet agents are fundamental to both primary and secondary prevention strategies in cardiovascular medicine. Their use necessitates a careful balance between achieving sufficient antithrombotic efficacy and minimizing the inherent risk of bleeding complications.

Learning Objectives

• Classify major antiplatelet drugs based on their molecular targets and mechanisms of action.
• Explain the pharmacodynamic principles underlying platelet inhibition for each drug class.
• Compare and contrast the pharmacokinetic profiles, including key metabolic pathways, of commonly used antiplatelet agents.
• Evaluate the approved clinical indications, major adverse effects, and significant drug interactions for antiplatelet therapy.
• Apply knowledge of pharmacogenomic and clinical factors to guide the selection and monitoring of antiplatelet drugs in special populations.

Classification

Antiplatelet drugs are systematically classified according to their primary molecular target or mechanism of action. This classification provides a framework for understanding their therapeutic applications and limitations.

Cyclooxygenase-1 (COX-1) Inhibitors

This class is represented predominantly by acetylsalicylic acid (aspirin). Aspirin irreversibly acetylates a serine residue (Ser⁵²⁹ in human COX-1) within the active site of the cyclooxygenase-1 enzyme, thereby blocking its catalytic activity.

P2Y₁₂ Receptor Antagonists

This heterogeneous class inhibits the adenosine diphosphate (ADP) P2Y₁₂ receptor on platelet surfaces, a key pathway for amplification of platelet activation. It is further subdivided:

• Thienopyridines: Prodrugs requiring hepatic bioactivation via cytochrome P450 enzymes. Examples include clopidogrel, prasugrel, and ticlopidine.
• Non-thienopyridines: Direct-acting, reversible antagonists. Examples include ticagrelor (a cyclopentyltriazolopyrimidine) and cangrelor (an ATP analog administered intravenously).

Glycoprotein IIb/IIIa (GP IIb/IIIa) Receptor Antagonists

These agents are parenteral inhibitors that block the final common pathway of platelet aggregation by preventing fibrinogen and von Willebrand factor binding to the activated GP IIb/IIIa integrin receptor. Members include abciximab (a monoclonal antibody fragment), eptifibatide (a cyclic heptapeptide), and tirofiban (a non-peptide tyrosine derivative).

Phosphodiesterase (PDE) Inhibitors

Drugs such as dipyridamole and cilostazol inhibit phosphodiesterase enzymes, leading to increased intraplatelet cyclic adenosine monophosphate (cAMP) levels, which suppresses platelet activation. Their mechanisms are pleiotropic and may involve other effects such as vasodilation.

Protease-Activated Receptor-1 (PAR-1) Antagonists

Vorapaxar is an oral antagonist of the thrombin receptor PAR-1, inhibiting thrombin-mediated platelet activation without affecting thrombin’s role in fibrin generation.

Other Agents

This category includes agents with less common or adjunctive mechanisms, such as nitric oxide donors, adenosine reuptake inhibitors, and thromboxane A₂ (TXA₂) receptor antagonists.

Mechanism of Action

The mechanism of action of antiplatelet drugs is defined by their specific interference with the sequential and synergistic pathways of platelet activation, which include initial adhesion, secretion, and ultimately aggregation.

Inhibition of Thromboxane A₂ Synthesis

Acetylsalicylic acid (aspirin) exerts its antiplatelet effect through irreversible inhibition of platelet cyclooxygenase-1 (COX-1). COX-1 catalyzes the conversion of arachidonic acid to prostaglandin G₂ and H₂, which are precursors for thromboxane A₂ (TXA₂). TXA₂ is a potent platelet agonist that promotes vasoconstriction and further platelet activation. By covalently modifying the enzyme, aspirin inhibits TXA₂ production for the entire lifespan of the platelet (7-10 days). The effect on endothelial cell COX-2, which produces prostacyclin (PGI₂, a platelet inhibitor and vasodilator), is transient due to the nucleated endothelial cells’ ability to synthesize new enzyme.

Antagonism of the ADP P2Y₁₂ Receptor

The P2Y₁₂ receptor is a Gi-protein coupled receptor central to sustained platelet activation and amplification. ADP released from dense granules of activated platelets binds to P2Y₁₂, leading to inhibition of adenylyl cyclase, lowered intraplatelet cAMP, and subsequent activation of the GP IIb/IIIa receptor. Inhibition of this receptor profoundly suppresses platelet aggregation.

• Thienopyridines (Clopidogrel, Prasugrel): These are prodrugs. Their active metabolites form a disulfide bridge with cysteine residues (Cys⁹⁷ and Cys¹⁷⁵) on the extracellular domain of the P2Y₁₂ receptor, causing irreversible antagonism. Prasugrel undergoes more efficient and consistent bioactivation than clopidogrel.
• Ticagrelor: This agent binds reversibly to the P2Y₁₂ receptor at a site distinct from the ADP binding pocket, inducing a conformational change that inhibits receptor function. Its action is non-competitive and reversible.
• Cangrelor: A direct-acting, reversible ATP analog administered intravenously with an immediate onset and rapid offset of action.

Blockade of the GP IIb/IIIa Receptor

The GP IIb/IIIa receptor (integrin α_IIbβ₃) is the most abundant platelet surface receptor. Upon platelet activation, a conformational change increases its affinity for fibrinogen and von Willebrand factor, allowing cross-linking of adjacent platelets. GP IIb/IIIa antagonists bind to this receptor, preventing ligand binding and thus blocking the final common pathway of aggregation.

• Abciximab: Binds non-competitively to the GP IIb/IIIa receptor with high affinity and a slow off-rate, also exhibiting cross-reactivity with the vitronectin receptor (α_vβ₃).
• Eptifibatide & Tirofiban: Competitive, reversible inhibitors that mimic the arginine-glycine-aspartate (RGD) sequence of natural ligands.

Increase in Intraplatelet cAMP

Phosphodiesterase inhibitors elevate intraplatelet cAMP, a key second messenger that inhibits platelet activation by decreasing cytosolic calcium levels and suppressing the activation of GP IIb/IIIa.

• Dipyridamole: Inhibits phosphodiesterase (primarily PDE5) and blocks adenosine reuptake, augmenting adenosine’s antiplatelet effects.
• Cilostazol: A selective inhibitor of PDE3, leading to increased cAMP. It also possesses vasodilatory properties.

Inhibition of Thrombin-Mediated Activation via PAR-1

Vorapaxar is a competitive antagonist of protease-activated receptor-1 (PAR-1). Thrombin cleaves the extracellular N-terminus of PAR-1, creating a new tethered ligand that activates the receptor. Vorapaxar binds to the receptor, preventing this thrombin-induced activation without interfering with thrombin’s proteolytic activity in the coagulation cascade.

Pharmacokinetics

The pharmacokinetic properties of antiplatelet drugs significantly influence their dosing regimens, onset and offset of action, and potential for drug interactions.

Absorption and Bioavailability

Oral bioavailability varies widely among agents. Aspirin is rapidly absorbed in the stomach and upper small intestine, with absorption kinetics influenced by formulation. Enteric-coated preparations delay absorption. Clopidogrel and prasugrel are prodrugs with good oral bioavailability, though prasugrel’s absorption is more rapid. Ticagrelor has a bioavailability of approximately 36%, and its absorption may be reduced by high-fat meals. Vorapaxar is well absorbed with an oral bioavailability estimated at 90% or greater. Intravenous agents like cangrelor and the GP IIb/IIIa inhibitors achieve immediate and complete bioavailability.

Distribution

Most antiplatelet drugs are extensively protein-bound. Aspirin and its metabolite salicylate are highly bound to albumin. Clopidogrel’s active metabolite is extensively bound. Ticagrelor and its active metabolite are highly bound to plasma proteins. The volume of distribution for these agents generally suggests widespread tissue distribution. Abciximab, due to its large molecular size, is largely confined to the intravascular space.

Metabolism

Metabolic pathways are critical, particularly for prodrugs, and are a major source of inter-individual variability in response.

• Aspirin: Rapidly hydrolyzed by esterases in the gut wall, liver, and plasma to salicylic acid, which is then metabolized by hepatic conjugation.
• Clopidogrel: Undergoes complex hepatic metabolism. Approximately 85% is hydrolyzed by esterases to an inactive carboxylic acid derivative. The remaining 15% undergoes a two-step oxidative process primarily mediated by CYP2C19, with contributions from CYP3A4, CYP2B6, and CYP1A2, to generate the active thiol metabolite. Genetic polymorphisms in CYP2C19 are a key determinant of clopidogrel responsiveness.
• Prasugrel: More efficiently metabolized than clopidogrel. It is rapidly hydrolyzed by esterases to a thiolactone intermediate, which is then converted to the active metabolite in a single oxidative step primarily by CYP3A4 and CYP2B6, with less dependence on CYP2C19.
• Ticagrelor: Primarily metabolized by CYP3A4 to an active metabolite (AR-C124910XX) which contributes to the pharmacologic effect. It is also a moderate inhibitor of CYP3A4 and P-glycoprotein.
• Ticagrelor and CYP3A4: Its metabolism is primarily via CYP3A4, forming an active metabolite.

Elimination and Half-Life

Elimination pathways and half-lives dictate dosing frequency and the duration of antiplatelet effect after discontinuation.

• Aspirin: The antiplatelet effect lasts for the platelet lifespan due to irreversible enzyme inhibition, despite a short chemical half-life of 15-20 minutes for aspirin itself.
• Clopidogrel: The active metabolite has a very short half-life (<1 hour), but its irreversible binding results in a pharmacodynamic effect that recovers as new platelets are produced over 5-7 days.
• Prasugrel: Active metabolite half-life is approximately 7 hours (range 2-15 hours), with irreversible receptor binding.
• Ticagrelor: Has a half-life of 7-9 hours, and its active metabolite has a half-life of 9 hours. Its reversible binding necessitates twice-daily dosing and allows for faster functional recovery (3-5 days) after discontinuation.
• Cangrelor: Has an extremely short half-life of 3-6 minutes, requiring continuous intravenous infusion and leading to rapid offset of effect within 1 hour.
• GP IIb/IIIa Inhibitors: Abciximab has a very short initial half-life (<10 minutes) but a prolonged terminal half-life due to tight receptor binding; platelet function may take 24-48 hours to recover. Eptifibatide and tirofiban have half-lives of 2-2.5 hours.
• Vorapaxar: Has a long terminal half-life (≈ 8 days) and an effective half-life of 3-4 days, reflecting slow receptor dissociation.

Therapeutic Uses/Clinical Applications

The clinical application of antiplatelet drugs is guided by robust evidence from large-scale randomized controlled trials, with indications spanning primary and secondary prevention across the cardiovascular spectrum.

Acute Coronary Syndromes (ACS) and Percutaneous Coronary Intervention (PCI)

Dual antiplatelet therapy (DAPT), combining a P2Y₁₂ inhibitor with aspirin, is the standard of care.

• Non-ST-Elevation ACS (NSTE-ACS) and ST-Elevation Myocardial Infarction (STEMI): A P2Y₁₂ inhibitor (clopidogrel, ticagrelor, or prasugrel) is initiated in addition to aspirin. Ticagrelor and prasugrel are generally preferred over clopidogrel in patients managed invasively due to superior ischemic outcomes, barring specific contraindications (e.g., prior stroke for prasugrel, high bleeding risk).
• PCI: DAPT is mandatory to prevent stent thrombosis. A loading dose of the P2Y₁₂ inhibitor is often given. Intravenous cangrelor or GP IIb/IIIa inhibitors may be used as bridging therapy or in high-risk PCI scenarios.
• Duration of DAPT: Typically prescribed for 6-12 months after ACS or drug-eluting stent implantation, though shorter (1-3 months) or longer (>12 months) durations may be considered based on ischemic vs. bleeding risk assessment.

Secondary Prevention of Atherothrombotic Events

• Chronic Coronary Artery Disease: Aspirin monotherapy (75-100 mg daily) is recommended for long-term secondary prevention. Clopidogrel is an alternative for aspirin-intolerant patients.
• Ischemic Stroke or Transient Ischemic Attack (TIA): Aspirin, clopidogrel, or the combination of aspirin with extended-release dipyridamole are used for secondary prevention. Short-term (21-90 days) DAPT with aspirin and clopidogrel may be considered for high-risk TIA or minor stroke.
• Peripheral Arterial Disease (PAD): Clopidogrel or aspirin is recommended. Cilostazol is indicated for the symptomatic treatment of intermittent claudication.

Primary Prevention

The role of aspirin in primary prevention has become more restrictive. It may be considered selectively in adults aged 40-70 years at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at increased bleeding risk, following shared decision-making.

Other Applications

• Atrial Fibrillation: Antiplatelet monotherapy is inferior to oral anticoagulation for stroke prevention and is rarely used. In selected patients with very low stroke risk, aspirin may be considered.
• Valvular Heart Disease: Aspirin may be added to vitamin K antagonist therapy in patients with mechanical heart valves. Its role in bioprosthetic valves is less defined.
• Vorapaxar: Approved for the reduction of thrombotic cardiovascular events in patients with a history of MI or PAD, as an adjunct to standard antiplatelet therapy (aspirin and/or clopidogrel). It is contraindicated in patients with a history of stroke, TIA, or intracranial hemorrhage.

Adverse Effects

The therapeutic action of inhibiting platelet function invariably increases the risk of bleeding, which represents the most significant class-wide adverse effect. Other organ-specific toxicities are also observed.

Bleeding

Bleeding complications range from minor (e.g., bruising, epistaxis) to major (e.g., gastrointestinal, intracranial). The risk is dose-dependent and potentiated by combination therapy.

• Major Bleeding: Defined as bleeding that is fatal, intracranial, leads to surgical intervention, or causes a significant drop in hemoglobin. The incidence varies by drug and clinical context; prasugrel and the GP IIb/IIIa inhibitors are associated with higher bleeding rates than clopidogrel.
• Intracranial Hemorrhage (ICH): A rare but devastating complication. The risk is increased with all antiplatelet agents, particularly in combination and in the elderly.
• Gastrointestinal Bleeding: A common site for major bleeding, especially with aspirin due to local mucosal injury and systemic inhibition of protective prostaglandins. Concomitant use of a proton pump inhibitor is often recommended for gastroprotection in high-risk patients.

Gastrointestinal Effects

Aspirin commonly causes dyspepsia, nausea, and abdominal pain. Higher doses can lead to gastritis, ulceration, and perforation. Clopidogrel may also cause gastrointestinal disturbances, though with less mucosal injury than aspirin.

Hematologic Effects

• Thrombocytopenia: A serious but uncommon effect. It is most notably associated with GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), occurring as an acute, profound thrombocytopenia within hours of initiation. It may be immune-mediated. Ticlopidine is associated with a risk of severe neutropenia and thrombotic thrombocytopenic purpura (TTP), limiting its use.
• Anemia: Can occur secondary to bleeding.

Other Organ System Effects

• Dyspnea: A characteristic side effect of ticagrelor, reported in 10-15% of patients. The mechanism may involve inhibition of adenosine reuptake by erythrocytes. It is often transient and rarely requires discontinuation.
• Bradycardia: Ticagrelor has been associated with ventricular pauses, particularly in the early phase of treatment.
• Headache and Flushing: Common with dipyridamole and cilostazol, related to vasodilation. These effects often diminish with continued use.
• Diarrhea: Associated with ticlopidine and, less commonly, clopidogrel.
• Hepatotoxicity: Ticlopidine can cause cholestatic jaundice. Other agents are rarely hepatotoxic.
• Hyperuricemia/Gout: Aspirin at low doses (≤2 g/day) can reduce renal urate excretion, potentially exacerbating gout.

Black Box Warnings

• Prasugrel: Contraindicated in patients with a history of transient ischemic attack or stroke due to an increased risk of intracranial hemorrhage and overall net harm demonstrated in this population.
• Ticagrelor: Carries a warning regarding bleeding risk and the requirement to avoid maintenance doses of aspirin above 100 mg daily, as higher doses reduce its effectiveness.
• Vorapaxar: Contraindicated in patients with a history of stroke, TIA, or intracranial hemorrhage due to a significant increase in the risk of ICH.

Drug Interactions

Drug interactions with antiplatelet agents can be pharmacokinetic or pharmacodynamic, often leading to an increased risk of bleeding or, less commonly, therapeutic failure.

Pharmacodynamic Interactions (Increased Bleeding Risk)

Concomitant use of other drugs that impair hemostasis synergistically increases bleeding risk.

• Anticoagulants: Warfarin, direct oral anticoagulants (DOACs), heparins. Triple therapy (DAPT plus an anticoagulant) significantly elevates bleeding risk and requires careful duration limitation and risk assessment.
• Other Antiplatelet Agents and NSAIDs: Combining different antiplatelet classes or adding non-selective NSAIDs (e.g., ibuprofen, naproxen) increases bleeding risk. NSAIDs may also competitively inhibit aspirin’s binding site on platelets.
• Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): May impair platelet serotonin uptake and increase bleeding tendency.
• Glucocorticoids: Increase the risk of gastrointestinal bleeding, particularly when combined with aspirin.

Pharmacokinetic Interactions

These interactions primarily affect the metabolism of P2Y₁₂ inhibitors.

• CYP2C19 Inhibitors and Clopidogrel: Drugs that inhibit CYP2C19 (e.g., omeprazole, esomeprazole, fluvoxamine, fluconazole, cimetidine) can reduce the formation of clopidogrel’s active metabolite, potentially diminishing its antiplatelet effect. The clinical significance of the omeprazole interaction is debated, but pantoprazole, which has weaker CYP2C19 inhibition, is often preferred if a PPI is needed.
• CYP3A4 Inducers/Inhibitors and Ticagrelor: Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) can decrease ticagrelor exposure, reducing efficacy. Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can increase ticagrelor exposure, raising bleeding risk. Ticagrelor itself is a moderate CYP3A4 inhibitor and can increase plasma concentrations of simvastatin and lovastatin.
• Prasugrel: Its metabolism is less susceptible to CYP interactions, though potent CYP3A4 inducers may theoretically reduce its efficacy.

Contraindications

Absolute contraindications typically include:

• Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage).
• History of severe hypersensitivity reaction to the drug.
• Specific contraindications as per black box warnings (e.g., prior stroke for prasugrel and vorapaxar).
• Severe hepatic impairment for some agents (e.g., caution with clopidogrel, prasugrel).

Special Considerations

The use of antiplatelet drugs requires tailored approaches in specific patient populations due to altered pharmacokinetics, pharmacodynamics, or risk-benefit ratios.

Pregnancy and Lactation

The benefits of antiplatelet therapy must be weighed against potential fetal and neonatal risks.

• Aspirin: Low-dose aspirin (75-100 mg/day) is considered compatible with pregnancy and is used for preeclampsia prevention in high-risk women. High-dose aspirin should be avoided, especially in the third trimester, due to risks of premature closure of the ductus arteriosus, oligohydramnios, and neonatal bleeding. It is excreted in breast milk in small amounts but is generally considered compatible with breastfeeding at low doses.
• Clopidogrel, Prasugrel, Ticagrelor: Human data are limited. Use during pregnancy is generally reserved for situations where the maternal benefit clearly outweighs potential fetal risk. These agents are not recommended during breastfeeding due to a lack of safety data.
• GP IIb/IIIa Inhibitors: Experience is extremely limited; use only if clearly needed.

Pediatric Population

Use is largely restricted to specific indications, most notably Kawasaki disease.

• Aspirin: Used in high doses for its anti-inflammatory effect in acute Kawasaki disease, followed by low-dose antiplatelet therapy until coronary artery abnormalities resolve. Its use in other pediatric conditions is rare due to the association with Reye’s syndrome, particularly with viral illnesses.
• Other Agents: Experience with P2Y₁₂ inhibitors and other antiplatelets in children is limited and typically occurs in the context of congenital heart disease, stents, or thromboembolic events, guided by specialist consultation.

Geriatric Population

Elderly patients (age ≥75 years) present a particular challenge due to increased prevalence of comorbidities, age-related changes in pharmacokinetics, and heightened risks of both thrombosis and bleeding.

• Increased Bleeding Risk: Age is an independent risk factor for major bleeding. Dosing adjustments may be necessary (e.g., prasugrel maintenance dose is reduced to 5 mg daily in patients ≥75 years).
• Altered Pharmacokinetics: Reduced renal and hepatic clearance may prolong the effects of some agents. Dose adjustment for eptifibatide and tirofiban is required in renal impairment, which is common in the elderly.
• Polypharmacy: Higher likelihood of drug interactions.
• Fall Risk: The consequence of bleeding from a fall is more severe, influencing the risk-benefit assessment for antiplatelet therapy.

Renal Impairment

Renal function primarily affects the elimination of drugs or active metabolites excreted renally.

• Clopidogrel, Prasugrel, Ticagrelor: No dosage adjustment is typically required. However, patients with renal impairment often have increased cardiovascular risk and may be more prone to bleeding.
• GP IIb/IIIa Inhibitors: Eptifibatide and tirofiban doses must be reduced in patients with renal insufficiency (creatinine clearance <50 mL/min). Abciximab does not require renal dose adjustment.
• Cilostazol: Dose reduction is recommended in patients with severe renal impairment.
• Dipyridamole: Caution is advised as the drug is renally excreted.

Hepatic Impairment

Hepatic dysfunction can impair the metabolism of many antiplatelet agents, potentially increasing drug exposure and bleeding risk.

• Clopidogrel and Prasugrel: As prodrugs requiring hepatic activation, their use in patients with severe hepatic disease may be unpredictable and is generally not recommended due to an increased bleeding risk.
• Ticagrelor: Exposure is increased in hepatic impairment. It is contraindicated in patients with severe hepatic impairment due to a lack of data and potential for increased bleeding.
• Aspirin: Should be used with caution; hypoalbuminemia may increase the concentration of free salicylate.
• Vorapaxar: Not studied in severe hepatic impairment; use is not recommended.

Summary/Key Points

• Antiplatelet drugs inhibit various pathways of platelet activation and aggregation, with aspirin (COX-1 inhibitor) and P2Y₁₂ receptor antagonists forming the backbone of most therapeutic regimens.
• Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y₁₂ inhibitor is standard for acute coronary syndromes and following percutaneous coronary intervention to prevent stent thrombosis and recurrent ischemic events.
• The pharmacokinetics of P2Y₁₂ inhibitors are crucial: clopidogrel is a prodrug with variable activation influenced by CYP2C19 genetics; prasugrel has more efficient activation; ticagrelor is direct-acting and reversible.
• Bleeding is the principal class-wide adverse effect. The risk is additive with combination therapy and potentiated by concomitant use of anticoagulants or NSAIDs.
• Significant drug interactions exist, particularly involving the cytochrome P450 system (e.g., CYP2C19 inhibitors with clopidogrel, CYP3A4 modulators with ticagrelor).
• Therapeutic decisions must be individualized, considering factors such as age, renal/hepatic function, bleeding risk, and specific contraindications (e.g., prior stroke for prasugrel and vorapaxar).

Clinical Pearls

• For a patient with ACS undergoing PCI, ticagrelor or prasugrel is generally preferred over clopidogrel unless contraindicated (e.g., prior stroke for prasugrel, high bleeding risk, or need for concomitant strong CYP3A4 inhibitor/inducer with ticagrelor).
• In patients requiring both antiplatelet therapy and gastroprotection, a proton pump inhibitor such as pantoprazole may be preferred over omeprazole due to a weaker potential interaction with clopidogrel metabolism.
• The dyspnea associated with ticagrelor is often benign and self-limiting; patient education can help avoid unnecessary discontinuation of an effective drug.
• Before elective surgery, the bleeding risk from antiplatelet drugs must be balanced against the thrombotic risk of stopping them. Aspirin is often continued, while P2Y₁₂ inhibitors are typically withheld for 3-7 days depending on the agent (shorter for ticagrelor, longer for clopidogrel/prasugrel). Bridging therapy is rarely needed.
• In patients with atrial fibrillation and coronary stents requiring triple therapy (DAPT + anticoagulant), the duration of triple therapy should be minimized (often 1-6 months) followed by a period of dual therapy (anticoagulant + single antiplatelet agent) to reduce bleeding risk.

References

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