Advantage of guided de-escalation of dual antiplatelet therapy seen in younger patients

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Dirk Sibbing

A pre-specified analysis of the TROPICAl-ACS study indicates that de-escalating dual antiplatelet therapy (DAPT), as guided by platelet function testing, after percutaneous coronary intervention (PCI) provides a net clinical benefit for patients aged ≤70 years.

Writing in the European Heart Journal, Dirk Sibbing (Department of Cardiology, LMU München, Munich, Germany) and others explain that “de-escalation” of DAPT involves prescribing a potent P2Y12 inhibitor (prasugrel was used in TROPICAl-ACS) and aspirin for one week after PCI, followed by clopidogrel for a week and a platelet function test. If a patient, while on clopidogrel, has high platelet reactivity, they are switched back to the potent P2Y12 inhibitor; if they have sufficient platelet reactivity, they remain on clopidogrel.

The main TROPICAL-ACS study (published in the Lancet last year) found that a de-escalation strategy was non-inferior—in terms of the combined primary endpoint of cardiac death, myocardial infarction, stroke, and bleeding—to a standard DAPT approach of aspirin and prasugrel in patients with acute coronary syndrome.

The aim of this pre-specified analysis of TROPICAL-ACS, Sibbing et al report, was to assess clinical outcomes in younger vs. elderly acute coronary syndrome patients with uniform prasugrel vs. guided DAPT de-escalation. “Patients’ age is a major determinate of outcomes after PCI in general and especially in conjunction with the use of P2Y12 inhibitors during and after PCI. Therefore, it seems mandatory to assess whether patients’ outcomes following de-escalation of antiplatelet treatment may differ in relation to age,” the authors comment. In this new analysis, a cutoff of 70 years was used—with younger patient being aged ≤70 years and older patients being aged >70 years.

Of the overall study population, 2,240 were aged ≤70 years (86%). In this younger population, the primary endpoint occurred in 5.9% of patients in the guided de-escalation group and 8.3% in the control group (p=0.03 for the difference). Additionally, Bleeding Academic Research Consortium (BARC) bleeding—a key secondary endpoint—was numerically lower in the de-escalation group (3.9% vs. 5.6% for the control group; p=0.06). Sibbing et al comment: “The absolute risk reduction of 2.4% observed for the primary endpoint corresponds to a number needed to treat of 42.”

However, among older patients, there were no significant differences between the de-escalation group and the control group in the rate of the primary endpoint; there were also no differences in bleeding between groups in this cohort of patients. The incidence of the primary endpoint, though, was significantly higher among older patients vs. younger patients (p<0.0001 for the difference).

According to the authors, using a STEPP analysis, increasing risk reduction was observed in the primary endpoint with decreasing age. They commented: “An exploratory post hoc analysis for interaction testing revealed 57 years of age as an optimal cutoff for separating age categories regarding possible net clinical benefit from guided DAPT de-escalation.” When this cutoff value was used, a significant benefit was seen for the de-escalation strategy: 3.9% vs. 7.7% (p=0.0006). “This overall benefit in the composite primary endpoint was largely driven by a significant reduction of bleeding in patients <57 years (p=0.0004),” Sibbing et al observe.

Concluding, they write: “The results suggest that guided de-escalation may be a safe and attractive alternative treatment concept for all acute coronary syndrome patients after PCI, while a significant benefit in bleeding may achieved in younger patients.”

Sibbing told Cardiovascular News: “Guided DAPT de-escalation reduces bleeding risk in younger patients and is attractive from an economic point of view for all acute coronary syndrome patients after PCI. Based on TROPICAL-ACS results, a de-escalation should be guided by platelet function testing and can be done as early as two weeks after discharge or at any time point later on. A single assessment of platelet inhibition on clopidogrel is needed and this seems feasible in clinical routine practice. This strategy must be considered as an alternative treatment concept and as a valid option for the treatment of acute coronary syndrome patients.”

Last year, the TOPIC study found that switching to clopidogrel after one month (after PCI) reduced bleeding without increasing ischaemic events in acute syndrome patients. 

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