Table 2.

Landmark trials of antiplatelet agents.

Year	Trial	Drug	Outcome
1988	ISIS-2	Aspirin	Aspirin became the mainstay of therapy in ST elevation myocardial infarction (STEMI)
1996	CAPRIE	Clopidogrel	Clopidogrel in comparison to aspirin led to fewer thrombotic events in patients who were post-MI, post-stroke, or had peripheral arterial disease (PAD)
2001	CURE	Clopidogrel	Addition of clopidogrel to aspirin resulted in 2% reduction in the risks for cardiovascular events including MI, stroke (MACCE), although with a 1% increase in major bleeding
2001	PCI CURE	Clopidogrel	Initiation of clopidogrel before PCI and its continuation for a mean of 8 months after PCI with stent implantation, along with aspirin provided considerable mortality benefit without significant increase in bleeding
2002	CREDO	Clopidogrel	Prolonged therapy with clopidogrel after PCI reduced the risk for death, MI and stroke by 3% at 1 year after randomization
2007	TRITON TIMI 38	Prasugrel	In patients with ACS and scheduled PCI, prasugrel demonstrated superior efficacy compared to clopidogrel in reducing ischemic events including stent thrombosis but with significantly higher bleeding
2009	PLATO	Ticagrelor	In patients with ACS, ticagrelor reduced rates of cardiovascular(CV) death, MI, or stroke and all-cause mortality at 12 months in comparison with clopidogrel without a significant difference in major bleeding. There was more non-CABG-related bleeding in the ticagrelor group. These benefits were less prominent in the USA cohort. The 2012 post-hoc analysis accounted for only aspirin dose for such a difference (2012-mahaffey)
2012	TRILOGY ACS	Prasugrel	Among patients with unstable angina (UA) or myocardial infarction without ST-segment elevation (NSTEMI), prasugrel did not significantly reduce the frequency of CV death), MI, or stroke, as compared with clopidogrel, and similar risks of bleeding were observed.
2013	CHAMPION PHOENIX	Cangrelor	Potent intravenous adenosine diphosphate (ADP) receptor antagonist was evaluated in patients undergoing elective or urgent PCI in comparison with standard therapy. There were 1.2% fewer MACCE events including ST in cangrelor arm without any significant increase in severe bleeding
2012	TRACER investigators	Vorapaxar	Oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation was evaluated in patients with ACS. There was no significant reduction in MACCE but it accounted for significant increase in the risk of major bleeding, including intracranial hemorrhage (ICH). Later, it was shown to reduce MACCE by about 1.2% in comparison with standard therapy in stable patients but at the cost of increased risk of moderate or severe bleeding including ICH

MACCE = major adverse cardiovascular and cerebrovascular events; ICH = intracranial hemorrhage. ISIS-2 [25] = Second International Study of Infarct Survival Collaborative Group; CAPRIE [26] = a randomized, blinded, trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events; CURE [27] = Clopidogrel in Unstable angina to prevent Recurrent Events; PCI-CURE [28] = Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention; CREDO [29] = The Clopidogrel for the Reduction of Events During Observation; TRITON-TIMI 38 [30] = TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction, PLATO [31] = Platelet inhibition And patient Outcomes; TRILOGY ACS [32] = The TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes; CHAMPION PHOENIX [33] = Effect of platelet inhibition with cangrelor during PCI on ischemic events; TRACER [34] = Thrombin-Receptor Antagonist for Clinical Event Reduction.