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TROPICAL-ACS: Guided de-escalation of antiplatelet therapy noninferior to standard treatment
In terms of net clinical benefit, guided de-escalation of antiplatelet treatment was noninferior to standard treatment with prasugrel at 1 year after PCI, according to the results of the TROPICAL-ACS trial published in The Lancet.
According to Dirk Sibbing, MD, from the department of cardiology at LMU München in Munich, and colleagues, for patients with ACS who undergo PCI, potent P2Y12 inhibitors such as prasugrel (Effient, Daiichi Sankyo/Eli Lilly) are the most effective anti-ischemic therapy in the early months after PCI, but they may confer bleeding risk when used chronically, and it may make sense to switch to a less potent antiplatelet drug such as clopidogrel for chronic use.
“This rationale has fueled interest in strategies of step-wise de-escalation using potent P2Y12 inhibitors only in the early phase of treatment and using the less potent clopidogrel during the chronic treatment course,” they wrote. “However, to date, the evidence supporting safety and efficacy and thereby justifying de-escalation is limited and the few available data from smaller studies are conflicting.”
Sibbing and colleagues conducted an investigator-initiated, randomized, open-label, assessor-blinded, multicenter trial across 33 sites in Europe between December 2, 2013 and May 20, 2016.
Patients were included in the study if they had biomarker-positive ACS treated successfully with PCI and a planned duration of dual antiplatelet therapy of 1 year.
Strategy feasible
Using an internet-based randomization procedure with a computer-generated block randomization with stratification across study sites, researchers assigned 2,610 patients to standard treatment with prasugrel for 12 months (n = 1,306; mean age, 59 years; 22% men) or a step-down regimen (n = 1,304; mean age, 59 years; 21% men).
The primary endpoint was net clinical benefit, defined as CV death, MI, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium (BARC) criteria at 1 year after randomization in the intention-to-treat population.
The researchers found that the primary endpoint occurred in 7% of the guided de-escalation group and in 9% of the control group (P for noninferiority = .0004; HR = 0.81; 95% CI, 0.62–1.06).
Although de-escalation was initiated early in the study, CV death, MI, or stroke occurred in 3% of both the de-escalation group and the control group (P for noninferiority = .0115).
There was no significant difference between the groups in BARC 2 or higher bleeding events (de-escalation group, 5%; control group, 6%; HR = 0.82; 95% CI, 0.59–1.13).
Research for the future
In a related editorial comment, Dominick J. Angiolillo, MD, PhD, FACC, professor of medicine, medical director of the Cardiovascular Research Program, program director of the Interventional Cardiology Fellowship Program and associate program director of the Cardiovascular Disease Fellowship at University of Florida College of Medicine–Jacksonville, wrote there may be a role for platelet function testing in this population.
“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,” Angiolillo, a member of the Cardiology Today’s Intervention Editorial Board, wrote. “Future research should build upon TROPICAL-ACS to help to define antiplatelet treatment approaches associated with optimal safety and efficacy performance profiles for the individual patient.”
The findings were also presented at the European Society of Cardiology Congress. – by Dave Quaile
Disclosure: The study was funded in part by Daiichi Sankyo, Eli Lilly and Roche Diagnostics. Angiolillo reports he has financial ties with Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Bristol-Myers Squibb, CeloNova, Chiesi, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani, Merck, Novartis, Osprey Medical, PLx Pharma, Pfizer, Renal Guard Solutions, Sanofi, St. Jude Medical and The Medicines Company. Sibbing reports receiving grant support from Daiichi Sankyo and Roche Diagnostics as well as personal fees from AstraZeneca, Bayer AG, Daiichi Sankyo, Eli Lilly, Merck Sharpe & Dohme, Pfizer and Roche Diagnostics. Please see the full study for a list of the other authors’ relevant financial disclosures.