Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes - TROPICAL-ACS

Jul 02, 2019
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Presenter/Author:
Dirk Sibbing, MD
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.
Date Presented:
08/27/2017
Date Published:
04/24/2019
Date Updated:
07/02/2019
Original Posted Date:
08/27/2017
References

Contribution To Literature:

The TROPICAL-ACS trial showed that de-escalation of maintenance antiplatelet therapy was noninferior to 1 year of prasugrel.

Description:

The goal of the trial was to evaluate de-escalation of maintenance antiplatelet therapy compared with control among patients who received a coronary stent for an acute coronary syndrome.

Study Design

  • Randomized
  • Parallel
  • Stratified

Patients with acute coronary syndrome who underwent percutaneous coronary intervention (PCI) were randomized to de-escalation of antiplatelet therapy (n = 1,304) vs. prasugrel for 12 months (n = 1,306). In the de-escalation group, participants were treated with prasugrel for 1 week, then clopidogrel for 1 week at which time they underwent platelet function testing. If high platelet reactivity was documented, they were switched back to prasugrel. Otherwise, they remained on clopidogrel for 1 year.

  • Total number of enrollees: 2,610
  • Duration of follow-up: 12 months
  • Mean patient age: 59 years
  • Percentage female: 78%
  • Percentage with diabetes: 22%

Inclusion criteria:

  • ST-segment elevation MI (STEMI) or NSTEMI
  • Underwent PCI
  • Planned use of prasugrel for 12 months

Other salient features/characteristics:

  • Presentation: STEMI in 55%, NSTEMI in 45%

Principal Findings:

The primary outcome, incidence of cardiovascular death, MI, stroke, or bleeding (Bleeding Academic Research Consortium [BARC] ≥2), occurred in 7% of the de-escalation group vs. 9% of the control group (p for noninferiority = 0.0004).

Cardiovascular death, MI, stroke, or BARC ≥2 bleeding for those ≤70 years: 5.9% of the de-escalation group vs. 8.3% of the control group (p = 0.03), and for those >70 years: 15.5% of the de-escalation group vs. 13.6% of the control group (p = 0.56) (p for interaction = 0.11).

However, there was significant treatment interaction when age was analyzed ≤57 years and >57 years (p for interaction = 0.03). Net clinical benefit was due to a reduction in major bleeding among younger patients who underwent de-escalation therapy.

Secondary outcomes:

  • All-cause mortality: 1% vs. 1% (p = 0.85), respectively, for de-escalation vs. control
  • MI: 2% vs. 2% (p = 0.59), respectively, for de-escalation vs. control
  • BARC type 3 or 5 bleeding: 2% vs. 1% (p = 0.63), respectively, for de-escalation vs. control
  • In the control group (n = 1,261), 15% of patients had high platelet reactivity despite being on prasugrel
  • Cardiovascular death, MI, or stroke: 4.8% among those with high platelet reactivity despite prasugrel compared with 2.2% among those with no high platelet reactivity on prasugrel (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.01-4.65, p = 0.049)
  • Low platelet reactivity was an independent predictor for bleeding (HR 1.74, 95% CI 1.18-2.56, p = 0.005) and there was no evidence for treatment interaction according to treatment groups (p for interaction = 0.76)

Interpretation:

Among patients with acute coronary syndrome (STEMI or NSTEMI), de-escalation of maintenance antiplatelet therapy was noninferior to 12 months of prasugrel. De-escalation of antiplatelet therapy was guided by platelet function testing. This strategy was associated with noninferiority regarding the primary outcome of cardiovascular death, MI, stroke, or bleeding BARC ≥2. Younger patients possibly experienced a greater net clinical benefit (due to less bleeding) compared with older patients with de-escalation of antiplatelet therapy. Especially if affordability of medications is an issue, this approach could be an alternative.

References:

Aradi D, Gross L, Trenk D, et al. Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial. Eur Heart J 2019;40:1942-51.

Sibbing D, Gross L, Trenk D, et al. Age and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: results from the randomized TROPICAL-ACS trial. Eur Heart J 2018;39:2749-58.

Sibbing D, Aradi D, Jacobshagen C, et al., on behalf of the TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndromes undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicenter trial. Lancet 2017;390:1747-57.

Editorial Comment: Angiolillo DJ. Dual antiplatelet therapy guided by platelet function testing. Lancet 2017;390:1718-20.

Presented by Dr. Dirk Sibbing at the European Society of Cardiology Congress, Barcelona, Spain, August 27, 2017.

Keywords: Acute Coronary Syndrome, Anticoagulants, Blood Platelets, ESC Congress, ESC2017, Hemorrhage, Myocardial Infarction, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Stents, Stroke


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