This article is more than 5 years old. Information may no longer be current.
OPTIMUS-5: Vorapaxar plus DAPT reduces thrombogenicity
PARIS — When added to dual antiplatelet therapy, vorapaxar reduced platelet-mediated thrombogenicity without impacting clot kinetics in patients with and without diabetes, according to results from the OPTIMUS-5 study presented at the European Society of Cardiology Congress.
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 program at the University of Florida College of Medicine–Jacksonville, and colleagues evaluated whether the pharmacodynamic effects of vorapaxar (Zontivity, Deerfield) differed between patients with diabetes and those without it.
The pharmacodynamic analysis, which was simultaneously published in JACC: Basic to Translational Science, included 64 patients (30 with diabetes) with prior MI or peripheral artery disease.
“We had learned from prior clinical trial experience, particularly the TRA 2P-TIMI 50 study, that vorapaxar was associated with an enhanced clinical benefit in our patients with diabetes,” Angiolillo told Healio. “It was used on top of standard therapy, mostly aspirin and clopidogrel, and reduced the primary ischemic endpoint at the cost of increased risk for bleeding, most prominently in patients with diabetes. To expand on this, we wanted to evaluate if these clinical differences could be attributed to any pharmacodynamic differences between diabetic and non-diabetic patients.”
The primary endpoint was maximum platelet aggregation, a marker for thrombogenicity.
The researchers found that adding vorapaxar to clopidogrel plus aspirin was linked with complete blockade of thrombin receptor activating peptide-induced platelet aggregation (P < .001), which was maintained after aspirin was discontinued (P < .001). The effect was consistent between those with and without diabetes, according to the researchers.
Angiolillo, a Cardiology Today’s Intervention Editorial Board Member, and colleagues also found that vorapaxar did not affect clot kinetics, including speed of thrombin generation, and that this effect was also consistent after discontinuation of aspirin and regardless of diabetes status.
Maximum platelet aggregation was reduced by vorapaxar when added to DAPT in patients with and without diabetes (P < .001 for both), but was increased in both groups when aspirin was discontinued (P = .01 for diabetes, P = .003 for no diabetes), the researchers found. They also found that overall, platelet aggregation was significantly reduced compared with baseline after aspirin withdrawal in patients without diabetes (P < .001) but not in patients with diabetes.
Adding vorapaxar did not affect markers impacting P2Y12 inhibition, but after aspirin withdrawal, there were increases in markers sensitive to COX-1 blockade, according to the researchers.
“Vorapaxar did what it was supposed to do to an equal extent, irrespective of diabetic status,” Angiolillo told Healio. “It completely abolished TRAP-induced platelet aggregation. It affected pharmacodynamic profiles without interfering with thrombin generation. What we see from a clinical standpoint is not related to any specific effect of vorapaxar on diabetic platelets, but the clinical benefit is more related to the higher underlying risk of diabetic patients.” – by Erik Swain
Reference:
Angiolillo DJ, et al. Abstract P1930. Presented at: European Society of Cardiology Congress; Aug. 31 to Sept. 4, 2019; Paris.
Franchi F, et al. JACC Basic Transl Sci. 2019;doi:10.1016/j.jacbts.2019.07.011
Disclosure: The study was investigator-initiated and was initially funded by Merck, with additional funding from the University of Florida-Jacksonville College of Medicine. Deerfield paid a nominal fee for the final phases of the study. Angiolillo reports he received consultant fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, CeloNova, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, St. Jude Medical and The Medicines Company and received institutional research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical and Renal Guard Solutions. Please see the study for the other authors’ relevant financial disclosures.