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Antiplatelet Drugs

A role in the prevention and acute treatment of arterial thrombosis

Antiplatelet agents have proven efficacy in the acute treatment and prevention of arterial thrombosis.95 As with anticoagulants, all available antiplatelet agents increase the risk of bleeding. Clinical decision-making must always balance the risks and benefits of treatment.

The antithrombotic effect of Aspirin

Aspirin irreversibly inhibits the COX-1 enzyme, thereby blocking production of thromboxane A2 (TXA2) in platelets.107 TXA2 is a potent platelet activator (along with ADP, collagen, and thrombin). Platelets cannot synthesise new proteins, so a single dose of Aspirin suppresses TXA2 production for the life of the platelet.
Aspirin exerts a maximal antithrombotic effect at a dose of 100 mg, which is considerably lower than the dose typically used for analgesic or anti-inflammatory effects. Low-dose Aspirin therapy has a modest antithrombotic effect, preventing approximately 25% of cardiovascular events when used to prevent recurrent coronary thrombosis. A possible reason for this modest effect is that other platelet activators, not inhibited by Aspirin, may compensate for the lack of TXA2.107, 108
Because of its antiplatelet effects and its suppressive effects on gastric mucosal protection, gastrointestinal (GI) bleeding is the major side effect of Aspirin use. The incidence in patients without other risks for GI bleeding is relatively low (1 to 2 per 1000 patient-years), so for many patients the benefits of low-dose Aspirin in secondary cardiac prevention far outweigh the risks.107

Thienopyridines

The two thienopyridines in clinical use are clopidogrel and ticlopidine. These medications are marginally superior to Aspirin in preventing atherothrombosis in the cerebral and peripheral arteries but not in the coronary arteries. In patients at high risk of recurrent coronary ischaemia, thienopyridines are often used in combination with Aspirin for a synergistic antithrombotic effect.108
Clopidogrel exerts its antiplatelet effects by irreversibly binding to the ADP receptor P2Y12.107 Because the onset of clopidogrel action is slow, a loading dose is used when rapid antithromboitc effects are needed, as in acute coronary syndrome. Repeated daily doses produce a steady state after four to seven days, and platelet function returns to normal a week after the last dose.107
Ticlopidine, the older of the two agents, causes neutropenia in 2% of patients, while clopidogrel does not. For this reason, clopidogrel is the preferred drug in this class.108 The major side effect of clopidogrel, like Aspirin, is GI bleeding. The haematologic disorder thrombotic thrombocytopenic purpura is a rare adverse event associated with clopidgrel.109

Glycoprotein IIb/IIIa complex inhibitors

The glycoprotein IIb/IIIa complex (GpIIb/IIIa) is the primary receptor involved in platelet aggregation.107, 108 This receptor establishes links to other platelets by binding to fibrinogen. Three GpIIb/IIIa-inhibiting drugs are currently available for clinical use: abciximab, tirofiban, and eptifibatide. Abciximab is a humanised immunoglobulin fragment, while tirofiban and eptifibatide are smaller molecules that bind to GpIIb/IIIa, competing with fibrinogen. All three drugs must be administered intravenously. They are used to achieve antithrombotic effect during percutaneous coronary interventions and to treat acute coronary syndrome. The inhibitory effect of these medications is reversible.
As with other antithrombotic agents, bleeding is the most common adverse event. Transient severe thrombocytopenia has also been reported, most commonly with abciximab.

Phosphodiesterase inhibitors

Cyclic AMP and GMP function as intracellular signalling agents to inhibit platelet activation and aggregation. Phosphodiesterase inhibitors exert an antithrombotic effect by increasing levels of these cyclic nucleotides inside the platelet.107, 110
The phosphodiesterase inhibitor dipyramidole is available as a sustained-release oral agent. Dipyramidole is prescribed in combination with warfarin to prevent cardiac emboli in patients with mechanical heart valves and in combination with Aspirin for secondary stroke prevention. Cilostazol inhibits platelet phosphodiesterase 3 and blocks platelet aggregation stimulated by ADP. It is indicated for symptomatic peripheral artery disease.
Mechanical Devices >
  • 95 - Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008;451(7181):914-918.
  • 107 - Messmore HL Jr, Jeske WP, Wehrmacher W, et al. Antiplatelet agents: current drugs and future trends. Hematol Oncol Clin North Am. 2005;19(1):87-117, vi.
  • 108 - Roth GJ. Antiplatelet therapy. In: Colman RW, Clowes AW, George JN, Goldhaber SZ, Marder VJ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006:1725-1738.
  • 109 - Plavix [package insert]. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; 2007.
  • 110 - Beebe HG, Dawson DL, Cutler BS, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med. 1999;159(17):2041-2050.
Aspirin
The brand name of acetylsalicylic acid (ASA), an antithrombotic medication that prevents thrombosis by inhibiting the activity of platelets – a component of blood that helps to prevent blood loss.
Platelet
(Thrombocyte) Cell circulating in the blood that is involved in the cellular mechanisms of primary haemostasis leading to the formation of blood clots. When a blood vessel is injured, platelets gather at the site of injury and stick together to form a plug, thereby preventing blood loss.
Clopidogrel
Oral antiplatelet agent used in the treatment of coronary artery disease, peripheral vascular disease and cerebrovascular disease.
Acute coronary syndrome
This is an umbrella term used to cover any group of clinical symptoms compatible with acute myocardial ischaemia (chest pain due to insufficient blood supply to the heart muscle that results from coronary artery disease). Acute coronary syndrome covers the spectrum of clinical conditions ranging from unstable angina to STEMI and NSTEMI.
Warfarin
A vitamin K antagonist. Most commonly used oral anticoagulant in chronic prevention or treatment of VTE.

From the Image Library

Vein image 1: venous thrombus formation in cusps of veins Micrograph: deep vein thrombosis Patient figure: major veins and deep vein thrombosis (DVT) See all Venous Thrombosis

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Did You Know?

Heart attack, a leading cause of death in the developed world, is most often triggered by acute thrombus formation within a coronary artery.95

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