The Big Idea: the coxib crisis Iron, aspirin and heart disease risk revisited

摘要

Kuhn1 used the term ‘crisis’ for the chaotic situation provoked by an unresolved anomaly (i.e. a finding not explainable by a prevailing scientific paradigm). As a crisis evolves, the rules by which the old paradigm are applied to new findings become increasingly blurred. Kuhn's description of a paradigm in crisis1 applies accurately to recent discussions of the cardiovascular risks of the coxibs.2,3 Recognition of paradigm crises is problematic in all scientific fields; however, in medical science, failure to recognize and resolve an ongoing crisis can put lives at risk by delaying a necessary paradigm shift. nnThere had been a ‘working paradigm’, reviewed by Antman et al.2 in a paper that aptly presents the current crisis. Their account of the ‘tsunami of events’ following withdrawal of rofecoxib in 2004 suggests an ongoing paradigm crisis. By the early 1990s, the prevailing paradigm involved ‘the recognition that there are two different cyclooxygenases (COXs), which ‘led to the straightforward view that COX-2 is responsible for the adverse pro-inflammatory effects of prostanoids and that non-specific COX inhibitors cause bleeding by inhibiting COX-1 in platelets’.2 The paradigm encouraged development of COX-2 selective inhibitors to isolate an assumed anti-inflammatory mechanism of aspirin from the mechanism causing haemorrhage. nnWhich of the direct and indirect effects of long-term aspirin use is responsible for cardioprotection remains fundamentally a matter of speculation. There is no reliable proof that the mechanisms under most intense discussion are responsible for prevention of coronary events with regular use. The ‘working paradigm’2 has been overtaken by a paradigm crisis. The mechanism of benefit could be an unexpected effect of aspirin or it could be hidden within one of the known harmful effects of aspirin