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Antiplatelet Drugs in the Management of Cardiovascular Indications

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Abstract

Platelets play an integral role in primary hemostasis and in coronary atherothrombosis. Drugs such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS), vitamin E, and COX-2 inhibitors such as celecoxib (Celebrex) affect platelet function. Antiplatelet drugs such as ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor, and elinogrel inhibit the adenosine diphosphate receptors on the platelet surface. Other antiplatelet drugs such as abciximab, eptifibatide, and tirofiban, by inhibiting the glycoprotein IIb/IIIa receptors, inhibit the final common pathway of platelet aggregation. Vorapaxar and atopaxar inhibit PAR1 thrombin receptor-activating peptide (TRAP)-induced platelet aggregation. Given the several agonists involved in different pathways of platelet aggregation, the combination of two antiplatelet drugs may be quite a rational approach in order to boost antithrombotic efficacy. Caution is needed in selecting the types of antiplatelet drugs as a combination therapy and their respective dosages in order to avoid serious bleeding complications. Several tests for monitoring antiplatelet drugs are available. The search for an ideal antiplatelet drug and also an ideal test for monitoring its effects continue.

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Abbreviations

Aspirin:

It is a salicylate, often used as an analgesic, antipyretic, anti-inflammatory, and antiplatelet drug. It has antiplatelet effect by its virtue of irreversibly inhibiting the cyclooxygenase pathway and thereby inhibiting the production of thromboxane. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2 that normally produces prostanoids which are mostly proinflammatory. Aspirin-modified prostaglandin endoperoxide synthase (PTGS2) enzyme produces lipoxins which are mostly anti-inflammatory.

CILON-trial:

Influence of cilostazol-based triple antiplatelet therapy on ischemic complication after drug-eluting stent implantation trial.

CLEAR PLATELETS 1b study:

Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting.

COMMIT trial:

Clopidogrel and Metoprolol in Myocardial Infarction Trial.

COX-2 inhibitors:

Newer NSAIDS (coxibs) developed to inhibit only PTGS2 with the intent to reduce the incidence of gastrointestinal side effects. Several coxibs have been withdrawn from the market after evidence emerged that PTGS2 inhibitors increase the risk of heart attack and stroke.

CREDO trial:

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention.

CRUSADE trial:

Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative.

CURRENT-OASIS 7 trial:

Double-dose versus standard dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes.

DAPC study:

The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type 2 diabetes mellitus: principal results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) study, a randomized trial.

EPIC trial:

Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty.

EPILOG trial:

Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization.

ESPRIT:

A randomized controlled trial on aspirin plus dipyridamole versus aspirin alone after cerebral ischemia of arterial origin randomized controlled trial.

INNOVATE-PCI trial:

A randomized, double-blind, active controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention.

OPTIMUS-2 study:

A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease in dual antiplatelet therapy.

PCI-CURE study:

Pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary interventions.

PERFORM study:

Rationale and design of the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack.

PLATO substudy:

PLATelet inhibition and patient outcomes.

PRISM-PLUS study:

Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction.

PURSUIT trial:

Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrin therapy.

RAPID trial:

Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet inhibitor Drugs) primary PCI study.

RESPOND trial:

Responses to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies.

S-ACCESS study:

Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): a randomized, double-blind, aspirin-controlled trial.

SIFA Trial (Studio Italiano Fibrillazione Atriale):

Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation.

TIMI 14 trial:

Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction.

TRA-2P-TIMI 50 trial:

Vorapaxar in the secondary prevention of atherothrombotic events.

TRITON-TIMI 38:

A double-blind, randomized controlled trial on prasugrel compared with clopidogrel in patients undergoing percutaneous coronary interventions for ST-elevation myocardial infarction.

vITAL-1 trial:

Study of ARC1779 in patients with acute myocardial infarction undergoing PCI.

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Authors and Affiliations

  1. Departments of Pathology and Pharmacology, Loyola University Medical Center, Chicago, IL, USA

    Prof. Jawed Fareed Ph.D.

  2. Loyola University Medical Center, Maywood, IL, USA

    Dr. Daneyal Syed

  3. Department of Pathology, Loyola University Health System, 160 S. First Avenue, Building 102 – Room 2646, 60153, Maywood, IL, USA

    Dr. Omer Iqbal

Authors
  1. Prof. Jawed Fareed Ph.D.
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  2. Dr. Daneyal Syed
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  3. Dr. Omer Iqbal
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Correspondence to Omer Iqbal .

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  1. Akademisches Lehrkrankenhaus MLU, Bitterfeld-Wolfen, Germany

    Peter Lanzer

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Fareed, J., Syed, D., Iqbal, O. (2014). Antiplatelet Drugs in the Management of Cardiovascular Indications. In: Lanzer, P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37393-0_218-1

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  • DOI: https://doi.org/10.1007/978-3-642-37393-0_218-1

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