Milestones in Antiplatelet Drugs
An article on antithrombotic therapy by Jack Hirsh, MD, and these accompanying milestones were published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.
Aspirin
| 1899 | Aspirin is introduced for pain and fever control by a German scientist and is patented in 1900. |
| 1960s | Scientists demonstrate that aspirin impairs platelet aggregation and prevents arterial thrombosis in experimental animals. |
| 1975 | Aspirin's mechanism of action is determined by scientists from Washington University in St. Louis. |
| 1978 | The first randomized trial showing the beneficial effects of aspirin is reported by a Canadian group who show that aspirin reduces the risk of stroke in patients with minor strokes. Soon after, several clinical trials demonstrate that aspirin is effective in treating heart attacks and stroke. |
ADP-Receptor Antagonists
| 1980s | The irreversible platelet ADP antagonist ticlopidine is developed and later shown to be effective in stroke patients in 1989. |
| 1990s | Clopidogrel, an analogue of ticlopidine, is developed and shown to be effective clinically. |
| 2001 | The combination of clopidogrel and aspirin proves to be effective in patients with acute coronary syndrome. |
GPIIb/IIIa-Receptor Antagonists
| 1970s/1980s | The glycoprotein IIb/IIIa (GPIIb/IIIa) receptor is found to mediate platelet aggregation by binding to soluble adhesive proteins. |
| 1990s | Monoclonal antibodies to block the GPIIb/IIIa receptor are developed and show promise as an antithrombotic treatment. |
| Soon after, a region of the monoclonal antibody c7E3 Fab (abciximab, ReoProTM) is found to be effective in patients with coronary stents; several studies then identify a pivotal role that the blockage of GPIIb/IIIa has in the management of acute coronary syndromes. Small intravenous GPIIb/IIIa antagonists are then developed and shown to be effective. |
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