Related Experiment Video
Updated: May 10, 2026
07:40
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
[Clopidogrel plus acetylsalicylic acid: a deadly combination].
1UMC St Radboud, afd. Farmacologie-Toxicologie, Nijmegen, the Netherlands. g.rongen@pharmtox.umcn.nl
Nederlands Tijdschrift Voor Geneeskunde
|June 20, 2013
Summary
Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in patients with lacunar cerebral infarcts and coronary atherosclerosis. This combination therapy should be discontinued due to lethal toxicity and bleeding risks.
Area of Science:
- Cardiology
- Neurology
- Pharmacology
Background:
- The SPS3 trial indicated increased mortality with clopidogrel plus aspirin versus aspirin alone in lacunar infarct patients.
- Dual-antiplatelet therapy (DAPT) is commonly used, but its safety profile requires ongoing evaluation.
Purpose of the Study:
- To review trial data on clopidogrel/aspirin DAPT, considering between-trial variations in mortality.
- To investigate the potential 'off-target' lethal toxicity of clopidogrel/aspirin combination therapy.
Main Methods:
- Meta-analysis of available trial data on clopidogrel/aspirin therapy.
- Comparative analysis of mortality rates across different control groups in relevant trials.
Main Results:
- Clopidogrel plus aspirin demonstrated lethal toxicity in patients with lacunar cerebral infarcts and coronary atherosclerosis.
- An alternative P2Y12 antagonist showed a survival benefit over clopidogrel, suggesting an 'off-target' effect of clopidogrel/aspirin.
Conclusions:
- The clopidogrel/aspirin combination therapy is associated with increased mortality and serious bleeding complications.
- Discontinuation of clopidogrel in combination with aspirin is recommended; future trials should evaluate alternative P2Y12 antagonists.
Related Concept Videos
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:27Coronary Artery Disease V: Interprofessional Care
Interprofessional care for coronary artery disease includes pharmacological therapy and revascularization procedures.Pharmacological therapy for Coronary Artery Disease (CAD) aims to manage symptoms, prevent complications, and improve patient outcomes through various classes of medications:Antiplatelet Agents:Aspirin and Clopidogrel: These medications inhibit platelet aggregation, preventing blood clots, which is crucial for avoiding heart attacks and strokes. Doctors often prescribe these...
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
01:27Combined Effects of Drugs: Synergism
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
01:28Acute Coronary Syndrome IV: Interprofessional Care
IntroductionThe management of Acute Coronary Syndrome (ACS) aims to minimize myocardial damage, preserve myocardial function, and prevent complications.Initial ManagementInpatient management involves continuous cardiac monitoring, preferably in an ICU, focusing on blood pressure, serum sodium, potassium, and creatinine levels, and urine output. Ongoing pharmacologic management is crucial for stabilizing the patient.Supplemental Oxygen: Administer supplemental oxygen if oxygen saturation is...