According to this study, presented during the ESC 2019 scientific sessions, non-ST acute coronary syndrome (NSTE-ACS) patients treated with ticagrelor presented a significantly higher risk of bleeding than patients treated with clopidogrel, with no counterbalance by higher benefit in thrombotic events.

Researchers suggest clopidogrel might be the gold standard for this elderly NSTE-ACS population, though clinical criterion remains vital to assess the adequate antithrombotic treatment on a case by case basis. Age is just one of the factors involved, we should see the whole picture, and those at higher risk are the most fragile patients.

The paradigm, based on the PLATO outcomes, used to be that all patients, regardless age, should receive ticagrelor. The present study adds an alternative we had learned to consider obsolete.

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The PLATO, published in NEJM ten years ago, had taught us ticagrelor reduces the risk of cardiovascular death, infarction and stroke in ACS patients with and without ST elevation, compared against clopidogrel. Ticagrelor was associated to increased major bleeding, though the net clinical benefit in the general population continued to favor it. Something similar was observed in the TRITON-TIMI 38 with prasugrel.

Based on these large studies, the current European guidelines recommend dual antiplatelet antiaggregation therapy for at least 12 months. Ticagrelor is the preferred one for all patients with moderate to high ischemic risk regardless revascularization strategy, while prasugrel is recommended for patients undergoing PCI (they both are evidence level B class 1). Clopidogrel, however, is reserved only for patients intolerant to ticagrelor/prasugrel, or for patients that required additional anticoagulation.

Only between 10% to 15% of these large studies were patients older than 75.

The POPULAR AGE study randomized 1003 elderly patients (all older than 70, mean 77 years of age) undergoing NSTE-ACS to 75 clopidogrel/day vs. one more powerful P2Y12 inhibitor. Deciding between ticagrelor or prasugrel was up to the treating physician, but most of them (98%) chose ticagrelor.

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The most frequent cause to interrupt ticagrelor was bleeding (primary end point component).

Major bleeding in this study resulted twice as higher for those receiving ticagrelor/prasugrel vs. clopidogrel (8.0% vs 4.4%; p= 0.02). This far larger risk of bleeding was not counterbalanced by a higher efficacy in terms of death, infarction or stroke (12.8% with clopidogrel vs 12.5% con ticagrelor/prasugrel).

Original title: Randomized comparison of clopidogrel versus ticagrelor or prasugrel in patients of 70 years or older with non-ST-elevation acute coronary syndrome: POPULAR AGE.

Reference: Gimbel ME et al. Presentado en el ESC 2019, Paris, Francia. Agosto 31, 2019.

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