Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects. part 42
Both abciximab therapy and stenting were studied in the Controlled Abciximab (ReoPro) and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial of patients with MI. In this group of patients, who appeared to be at a relatively low risk (Table 8), abciximab had a beneficial effect in the PTCA group but did not affect death or reinfarction in the stent group.
Abciximab was compared to tirofiban as treatment for PCI in the TARGET study (Table 8). Abciximab treatment was found to be associated with a statistically significant lower rate of ischemic complications after 30 days, but at 6 months the differences were less appar
Five completed trials have examined the efficacy and safety of tirofiban, lamifiban (a nonpeptide GPIIb/IIIa blocker the development of which has been discontinued), and eptifibatide in approximately 25,000 patients with acute coronary syndromes without persistent ST-segment elevation who were randomized to receive a GPIIb/IIIa antagonist or placebo, in addition to conventional antithrombotic therapy (Table 9).i2,2 These studies demonstrated a 0 to 27% reduction in the RR of MI or death at 30 days. Both eptifibatide and tirofiban have received approval from the FDA for the treatment of acute coronary syndromes, including patients who are to be managed medically and those undergoing PCI. However, in the GUSTO IV-ACS trial, abciximab therapy (0.25 mg/kg bolus followed by a 0.125 g/kg/min infusion) for 24 or 48 h was not beneficial as a first-line medical treatment in patients with acute coronary syndromes. A meta-analysis of all major randomized clinical trials of GPIIb/IIIa antagonists in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularization suggested a 9% reduction in the odds of death or MI at 30 days. However, the true size of the additional benefit resulting from short-term, high-grade blockade of GPIIb/IIIa combined with standard antithrombotic therapy is somewhat uncertain, since the 95% CI ranged from 2 to 16%. Moreover, the 1% absolute difference in death or MI was balanced by an absolute excess of 1% in major bleeding complications associated with GPIIb/IIIa antagonists vs control. The Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B Investigators have reported that dose-titrated lamifiban had no significant effects on clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes and yet caused excess bleeding, thus reinforcing the uncertainty noted above. Of note, a subgroup analysis of these studies identified a consistent and significant mortality advantage for patients with diabetes, even in the GUSTO IV-ACS study, raising the possibility that platelets may play a more important role in the pathogenesis of the ischemic damage in diabetic patients.
