Original title: Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Reference: Lindholm D et al. Eur Heart J. 2014; Epub ahead of print.

The PLATO study randomized 18624 patients with ACS to aspirin and ticagrelor (180 mg loading dose followed by 90 mg every 12 hours) versus aspirin plus clopidogrel ( 300 or 600 mg loading dose followed by 75 mg every 24 hr.) The main results of the study were published in NEJM in 2009 and showed a reduction in the composite of death, myocardial infarction and stroke (primary end point) at 12 months, without increasing major bleeding. This substudy of PLATO analysed those patients admitted with non-ST elevation ACS and received revascularization within the first 10 days after admission to the hospital (5366 patients out of the 18624). 

Compared with clopidogrel, ticagrelor reduced the primary end point of efficacy (10% ticagrelor versus clopidogrel 12.3 %, p = 0.0013) which was a combination of cardiovascular death, heart attack and stroke. Ticagrelor also reduced infarction (6.6 % versus 7.7 %, P = 0.049), cardiovascular death (3.7 % versus 4.9 %, P = 0.007) and death from any cause (4.3 % versus 5.8 %, 0.002) when considered separately. Stroke incidence was similar between groups (1.3 % versus 1.4 %, P = 0.79). The primary end point of safety (major bleeding) was similar (13.4 % versus 12.6 %, P = 0.26) but an increase in bleeding not related to surgery in the ticagrelor group (4.8 % versus 3.8 %, p = 0.0139) was observed. While there was no difference in bleeding compromising life, fatal bleeding as well as in the intracranial bleeding, combined of major and minor bleeding was higher with ticagrelor. The event rate was significantly higher among patients who did not receive revascularization within the first 10 days compared with those revascularized. Beyond this, ticagrelor reduced the primary end point similarly in both groups of patients as well as death from any cause.

Conclusion

In patients with non-ST elevation ACS, ticagrelor was superior to clopidogrel in reducing ischemic events and mortality independently of revascularization or not within the first 10 days of the event. These results are consistent with the overall outcome of the PLATO study. 

Editorial comment

While current guidelines recommend an early invasive therapy in non-ST elevation ACS, in daily practice a significant number of patients are managed noninvasively, in part because of comorbidities as well as the bleeding risk. In these patients, the anti-aggregation strategy was unclear and, in fact, the TRILOGY -ACS study with prasugrel showed no advantages to 2 years in those not revascularized. 

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