Why is the use of clopidogrel increasing rapidly in Australia? An exploration of geographical location, age, sex and cardiac stenting rates as possible influences on clopidogrel use.

PURPOSE: To explore clopidogrel use within Australia, investigating geography, age, sex and cardiac stenting rates. METHODS: Data for clopidogrel supply (Pharmaceutical Benefits Scheme (PBS) and Repatriation Pharmaceutical Benefits Scheme (RPBS)) and cardiac stenting procedures (State Health Departments) were obtained for four different geographic regions (very remote/remote and major city in two Australian states). General linear modelling and correlation analyses were used to test for associations and chi2 analyses for proportions. RESULTS: Clopidogrel supply increased rapidly in Australia since introduction, from 1.2 to 9.0 Defined Daily Doses (DDD)/1000 population/day. Among concessional and veteran populations use was much higher. Analysis of geographical area data confirmed an association between clopidogrel supply rates and cardiac stenting rates (r = 0.8-0.9 Spearman's rho, p < 0.01). Sex, age and geographical location were associated with both rates when considered together and when considered independently. Further modelling indicated that between 30 and 73% of clopidogrel supply could be accounted for by people receiving cardiac stents. CONCLUSIONS: The supply of clopidogrel increases with age, male sex and living in a major city. These same demographic variables were important for cardiac stenting, an indication which is currently not approved for subsidy by the Australian government, but which modelling indicated could account for between one-third and three quarters of clopidogrel use. A review may be required to ensure subsidised indications reflect current evidence and cost-effective use.

Novel platelet inhibitors.

Platelet-inhibitory drugs are of proven benefit to individuals who suffer from atherosclerotic cardiovascular disease. Despite substantial effort to identify more potent platelet-inhibitory agents, aspirin, an irreversible inhibitor of platelet cyclooxygenase activity, remains the standard against which other drugs are judged. Drugs that appear to be at least as efficacious as aspirin in specific clinical settings include the thienopyridines ticlopidine and clopidogrel, specific inhibitors of ADP-stimulated platelet function, and the phosphodiesterase 3 inhibitor cilostazol. Ligand binding to the platelet integrin alphaIIbbeta3 (GPIIb-IIIa), a prerequisite for platelet thrombus formation, has been a prominent target for drug development. Currently, three types of alphaIIbbeta3 antagonists are available: the monoclonal antibody Fab fragment abciximab, cyclic peptides based on the Arg-Gly-Asp (RGD) or related amino acid motifs, and RGD-based peptidomimetics. The efficacy of each type of alphaIIbbeta3 antagonist in the setting of acute coronary artery disease has been confirmed in multicenter clinical trials.