Clinical and Economic Costs Compete in the De-Escalation of Antiplatelet Therapy

Patients undergoing primary angioplasty for ST-segment elevation acute myocardial infarction have similar clinical outcomes at 1 year regardless of whether they are treated with ticagrelor or prasugrel, according the PRAGUE-18 study.

This new substudy adds an interesting detail: patients who switched from prasugrel and ticagrelor to clopidogrel, citing economic reasons for the “de-escalation” of therapy, were not at an increased risk of ischemic events. In fact, patients who stayed on prasugrel and ticagrelor experienced more cardiovascular events than those who switched to clopidogrel (8.5% vs. 2.5%; p = 0.024), as well as a higher risk of bleeding (13.4% vs. 7.3%; p = 0.001).

Read also: “Aspirin During Noncardiac Surgery: Only in Patients with Prior Angioplasty”.

In contrast, patients who switched to clopidogrel for clinical (instead of economic) reasons did experience more events than those who stayed on prasugrel or ticagrelor.

Patients who switched for financial reasons did so immediately after hospital discharge (mean 8 days).

The outcomes of the PRAGUE-18 study comparing prasugrel and ticagrelor were presented last year at the European Society of Cardiology (ESC) Congress. The study was stopped early after enrolling 1230 of the projected 2500 patients due to similarities in the events experienced with both drugs.

Read also: “Endovascular Strategy Seems Superior against Surgery in Ruptured Aneurysms”.

At 1 year, the risk of cardiac death, nonfatal infarction, or stroke occurred in 6.6% of patients treated with prasugrel vs. 5.7% of those treated with ticagrelor, a nonsignificant difference that, in the interim analysis, warranted an early stop for study futility.

All patients were informed about the costs of prasugrel and ticagrelor, and that the intended treatment duration was 12 months. However, after being discharged, many of them were unable to afford the costs of these new P2Y12 inhibitors. The fact that clopidogrel is 100% reimbursed by medical insurance in the Czech Republic also factored in the equation.

De-escalation of antiplatelet therapy was quite common, with nearly 50% of patients switching from prasugrel to clopidogrel and 60% switching from ticagrelor to clopidogrel. The main reason for the switch was the cost of drugs.

Read also: “Closure of Patent Foramen Ovale for the Treatment of Migraine”.

In the SCOPE observational study, de-escalation was associated with an increase of ischemic events, while de-escalation was safe in the TOPIC study.

In this analysis, de-escalation for financial reasons was not only safe, but also showed that patients who switched experienced less events than those who stayed on the original medication. This detail, while interesting, can only serve to generate hypotheses. While patients were initially randomized to receive ticagrelor or prasugrel, subsequent de-escalation was absolutely arbitrary.

Confounding variables may abound, for example, as patients with good clinical outcomes undergo a successful primary angioplasty and then ask their primary care physician to switch therapies. In such a case, the physician obliges and indicates de-escalation to clopidogrel because s/he assesses the patient’s ischemic risk as low. In contrast, if a patient at high-ischemic risk makes the same request, the physician will advise him/her to make his/her best efforts to afford the new P2Y12 inhibitors.

Original title: One-Year Outcomes of Prasugrel Versus Ticagrelor in Acute Myocardial Infarction Treated with Primary Angioplasty: The PRAGUE-18 Study.

Reference: Motovska Z et al. J Am Coll Cardiol. 2017; Epub ahead of print.

We are interested in your opinion. Please, leave your comments, thoughts, questions, etc., below. They will be most welcome.