DAPT Can Be Safely De-Escalated Post-PCI Based on Platelet Function Testing
In TROPICAL-ACS, using clopidogrel for maintenance therapy in good responders was noninferior to 12 months of prasugrel.
BARCELONA, Spain—Switching from more potent antiplatelets to clopidogrel based on the results of platelet function testing shortly after PCI seems to be a viable option in patients with ACS, results of the TROPICAL-ACS trial suggest.
Patients who were tested about 2 weeks after successful PCI to determine whether they should move forward with clopidogrel or prasugrel as part of their dual antiplatelet therapy (DAPT) regimen had outcomes that were noninferior to those of patients who received prasugrel for 12 months, Dirk Sibbing, MD (Ludwig Maximilian University of Munich, Germany), reported at the European Society of Cardiology Congress 2017.
The rate of cardiovascular death, MI, stroke, or BARC grade ≥ 2 bleeding (primary endpoint) was 7.3% in the guided de-escalation group and 9.0% in the control group (P = 0.0004 for noninferiority). Key secondary endpoints, including BARC grade ≥ 2 bleeding alone and composite ischemic outcomes, did not differ between trial arms.
Sibbing told TCTMD that based on the findings, which were published simultaneously online in the Lancet, the de-escalation strategy tested in the trial should gain the attention of guideline-writing committees.
“The approach makes sense because sufficient platelet inhibition is guaranteed, and I think that upcoming guidelines should reflect it as an alternative strategy for patients deemed unsuitable for 1-year potent platelet inhibition,” he said, noting that the TROPICAL-ACS results have spurred even greater use of the method at his center.
The approach makes sense because sufficient platelet inhibition is guaranteed. Dirk Sibbing
Commenting for TCTMD, Neal Kleiman, MD (Houston Methodist Hospital, TX), said a question clinicians have had is whether they could use a more potent antiplatelet drug like prasugrel (Effient; Eli Lilly) or ticagrelor (Brilinta; AstraZeneca) to cover the high risk of stent thrombosis in the first week after PCI and then step back down to clopidogrel after that. When asked what TROPICAL-ACS means for that approach, he said, “I think it supports it. The question is how strongly does it support it.”
Kleiman expressed concerns about the sample size of the trial, the low number of endpoint events, the short duration of initial prasugrel treatment in the de-escalation arm, and the use of a platelet function test that is not commercially available in the United States.
Even so, he said the trial probably provides enough support for a class IIa or IIb recommendation in future guidelines. And if another trial—particularly one conducted using a platelet function test widely available to US clinicians—were to replicate the findings, that would probably support a class I recommendation for the guided de-escalation approach tested in TROPICAL-ACS, Kleiman added.
De-escalation Common in Clinical Practice
Current guidelines preferentially recommend platelet inhibition with prasugrel or ticagrelor in patients with ACS, but those agents, though they have an advantage over clopidogrel for reducing ischemic events, carry higher bleeding risks. Those risks—along with accompanying concerns over side effects and drug costs—sometimes lead clinicians to switch patients from the more potent agents to clopidogrel. Sibbing said such de-escalation is common and cited the TRANSLATE-ACS registry, which showed that the shift occurred in more than 20% of patients.
TROPICAL-ACS was designed to evaluate a de-escalation strategy using platelet function testing, which was introduced to account for the large variability seen in response to clopidogrel. The trial, conducted at 33 sites in Europe, included 2,610 patients with biomarker-positive ACS (about 56% STEMI and 44% NSTEMI) who underwent successful PCI and were discharged with a plan for 12 months of DAPT.
Patients randomized to the control group were discharged on prasugrel, had a platelet function test (Multiplate analyzer; Roche Diagnostics) performed at 14 days, and then continued with prasugrel through 1 year. Those randomized to de-escalation were discharged on prasugrel, but after 7 days, they started taking clopidogrel. After another week, a platelet function test was performed. Patients with high platelet reactivity (40% of patients in that arm) were transitioned back to prasugrel, whereas those with low platelet reactivity continued on clopidogrel for the rest of the first year.
The trial established that the de-escalation strategy was noninferior to the standard approach in terms of the net clinical benefit primary endpoint, but there were hints of greater benefits in certain subgroups. There was a significant interaction (P = 0.01) indicating that patients with STEMI fared better with the de-escalation approach, with no such benefit seen in the NSTEMI group. Patients 70 and younger also seemed to do better with de-escalation, although the interaction with age was not statistically significant.
Platelet Function Testing Finds Its Way?
In an accompanying editorial, Dominick Angiolillo, MD, PhD (University of Florida College of Medicine-Jacksonville), notes that platelet function testing has struggled to find a place in routine clinical practice because of several trials—TRIGGER-PCI, GRAVITAS, ARCTIC, and ANTARCTIC—showing that such testing to guide management does not improve clinical outcomes.
“The experience from previous studies led to the design of the TROPICAL-ACS trial, the results of which now provide additional insights on how to use [platelet function testing] to help select a P2Y12 inhibitor, thus suggesting a potential resurgence of a nearly abandoned instrument,” he writes.
Although there are some limitations, Angiolillo says, “based on the noninferiority trial design, the take-home message of TROPICAL-ACS is that, in patients with acute coronary syndrome undergoing PCI, [platelet function testing]-guided selection of P2Y12-inhibiting therapy could represent an alternative approach to a standard strategy of prasugrel use.”
Sibbing stressed to TCTMD that the de-escalation strategy studied in the trial would not be used for all patients with ACS. Both he and Angiolillo envision the approach being most useful in patients who are not suitable for extended treatment with prasugrel or ticagrelor, such as those with high bleeding risks or those who might have trouble paying for the more expensive agents.
“Indeed, bleeding concerns and socioeconomic factors are key contributors to de-escalation therapy in real-world practice,” Angiolillo notes.
Sibbing D, Aradi D, Jacobshagen C, et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017;Epub ahead of print.
Angiolillo DJ. Dual antiplatelet therapy guided by platelet function testing. Lancet. 2017;Epub ahead of print.
- TROPICAL-ACS was sponsored by Klinikum der Universität München and financially supported by a research grant from Roche Diagnostics. Prasugrel purchase, drug delivery, and related logistics were supported by Eli Lilly and Daiichi-Sankyo.
- Sibbing reports receiving grants from Roche Diagnostics and Daiichi-Sankyo during the conduct of the study; and personal fees from Bayer AG, Daiichi-Sankyo, Eli Lilly, Roche Diagnostics, Merck Sharp & Dohme, Pfizer, and AstraZeneca not related to the study.
- Angiolillo reports numerous relationships with industry.
- Kleiman reports no relevant conflicts of interest.