The FDA report on vorapaxar in the elderly: A convoluted dilemma.
There are consistent data suggesting that elderly patients benefit from less aggressive antiplatelet strategies following acute coronary syndromes. This observation is likely because advanced age is associated with greater bleeding and potentially less efficacy. Oral antiplatelet agents are often prescibed uniformly, without dose adjustments, representing a concerning reality for this patient population. Vorapaxar, a platelet thrombin PAR-1 inhibitor, has been evaluated in the TRA2P and TRACER trials, but drug efficacy and safety, with respect to age, were not discussed in detail. We sought to define the FDA-confirmed age-dependent clinical outcomes after vorapaxar. The mean and median ages in the TRA2P indicated population were about 60 years, with 33.4% greater than 65 years of age and 9.2% greater than 75 years of age. Vorapaxar efficacy was reduced in those aged 72 or older, while bleeding rates gradually increased with age for both arms. For patients aged 75 or older, efficacy numerically favored vorapaxar, but this interaction was not statistically significant (HR=1.18; 95% CI=0.95-1.46; p=0.132). In TRACER, the point estimates by age quintile for the primary endpoint also favored vorapaxar, except for the lowest age quintile ≤56 probably due to overtreatment. GUSTO moderate/severe bleeding was substantially higher with vorapaxar in both trials for the eldest age quintile (5.1% placebo vs. 7.0% vorapaxar in TRA2P; 8.4% placebo vs. 13% vorapaxar in TRACER). In conclusion, the FDA analyses reassure that vorapaxar efficacy is not reduced in the elderly. However, the bleeding risk after vorapaxar is definitely increased with advancing age.
HeartDrug™ Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, MD 21204, USA. Electronic address: heartdrug@aol.com.
Victor L
VL
Serebruany
HeartDrug™ Research Laboratories, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, MD 21204, USA.
Seth D
SD
Fortmann
D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000368:Aged; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014481:United States; D014486:United States Food and Drug Administration
D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
Age; Bleeding; Clinical trials; Efficacy; Elderly; Vorapaxar