Table 2.
Summary of findings
| Ticlopidine (EMA approval in 1989; FDA approval in 1991) |
Clopidogrel (FDA approval in 1997) |
Prasugrel (FDA approval in 2009) |
|
|---|---|---|---|
| Systematic literature review (2001) | Ticlopidine was the leading cause of drug-induced TTP cases (12% of cases) | Clopidogrel accounted for 8% of all drug-induced TTP cases, second only to ticlopidine | No case of prasugrel-associated TTP is described in the literature |
| Adverse events reported in the FDA Adverse Event Reporting System database (1998–2011) | 1989–2001 (87 TTP cases); since 2002 (10 TTP cases); overall, ticlopidine is the fifth most frequent drug associated with TTP | 1998–2001 (57 TTP cases); since 2002, (140 TTP cases); overall, clopidogrel is the most frequent drug associated with TTP | In 2009 and 2010, 1 and 10 cases of prasugrel-associated TTP were reported to the FDA, respectively |
| Time from FDA approval to first case of TTP being reported | 2 years | 6 months | 6 months |
| Surveys of therapeutic plasma exchange directors (1998) | 98 ticlopidine-associated TTP patients; survival 60% with therapeutic plasma exchange; 20% without; onset < 2 weeks in 5% of patients | 11 clopidogrel-associated TTP cases (1 death); onset < 2 weeks in 91% of patients | Not applicable |
| Surveys of interventional cardiology centers (1998) | Five TTP cases among 8,000 ticlopidine users and nine TTP cases among 45,000 ticlopidine users; Estimated incidence: 1/1,600 to 1/5,000 ticlopidine-treated patients; onset between 2 and 12 weeks of exposure | No studies reported on this | Not applicable |
| Adverse event reports from Phase III clinical trials (1989–2010) | One TTP case in 2,932 ticlopidine-treated patients | Zero TTP cases in 27,961 clopidogrel treated patients | Zero TTP cases in 1,769 prasugrel-treated patients |
| Insurance claims files (United States) (1998–2001) | Two ticlopidine-associated TTP cases among 15 million person-years of observation | One clopidogrel-associated TTP case among 15 million person-years of observation | Not applicable |
| Insurance claims files (United States) (2001–2004) | Zero ticlopidine-associated TTP cases among 16.4 million person-years of observation | Zero clopidogrel-associated TTP cases among 16.4 million person-years of observation | Not applicable |
| Clinical findings from SERF-TTP (2003–2007) | Onset within 2 weeks, 10% (n = 93 patients); 86% survival with therapeutic plasma exchange, 46% without | Onset within 2 weeks, 74% (n = 35 patients); 72% survival with therapeutic plasma exchange, 67% without | No cases reported had onset beyond 2 weeks of drug initiation |
| Plasma samples from the SERF-TTP study (2003–2007); ADAMTS-13 deficiency | 80% (30 patients) | 0% (8 patients) | Not available |
| Plasma samples from the SERF-TTP study (2003–2007); neutralizing antibodies to ADAMTS-13 | 100% (30 patients) | 0% (8 patients) | Not available |
Abbreviations: ADAMTS-13, a disintegrin and metalloproteinase with a thrombospondin type 1motif,member 13; EMA, European Medicines Agency; FDA, U.S. Food and Drug Administration; SERF-TTP, Surveillance Epidemiology and Risk Factor for TTP; TTP, thrombotic thrombocytopenic purpura.