Equipoise ethics

Clinical equipoise was first proposed as a solution to the problem of randomisation 30 years ago. It is defined as a state of disagreement or uncertainty in the informed, expert medical community about the relative clinical merits of the intervention arms in a  This state of equipoise may mean that there is insufficient evidence to warrant a judgment that one intervention in the trial is inferior to the others. It may also mean that some experts favour one intervention over the others, but different experts prefer different interventions for the same  However, so long as one or both of these conditions apply to a trial, each of its arms is broadly consistent with competent medical care. This means that a patient can enrol in the trial without having to worry about being disadvantaged and a physician can refer patients without violating the duty of

Take home messages from the Steg et al. article and this illustrative case include the following:

  • Noninvasive testing remains very common (>60% of the cohort) despite the fact that guidelines tend to reserve recommendation for those with a change in symptom status. Because 80% of the cohort did not have angina, we could assume that a large portion of the testing was routine and probably outside of current guidelines. 7
  • Ischemia alone did not increase the risk of adverse CV events. There is extensive evidence suggesting that the burden of ischemia is a risk marker for adverse events, but this was not borne out in the current analysis. In addition, revascularization in subjects with documented CAD and ischemia did not reduce CV events in the COURAGE trial. 3 The COURAGE trial assumed knowledge of the coronary anatomy, but this was the case for the majority of subjects in CLARIFY. As such, one could argue that there was probably little justification for the majority of noninvasive testing in this population.
  • Angina was a powerful predictor of recurrent CV events in the cohort, especially when coupled with ischemia. As has been outlined in the guidelines, recurrent testing or revascularization is most appropriate in subjects with symptoms. In addition, medical therapy in chronic CAD remains very important, particularly in subjects with angina even in the absence of ischemia. The patient in this case was on optimal medical therapy except for the treatment of his dyslipidemia. The recent introduction of the PCSK9 inhibitors will allow us to achieve LDL-C treatment target and improve medical therapy. The controversial American College of Cardiology and American Heart Association dyslipidemia guidelines have been recently updated to include a recommendation about non-statin medications driven by data from recent randomized clinical trials. 8
  • There is still clinical equipoise for patients who have angina and ischemia documented by noninvasive testing. 4 This was not addressed by Steg et al. Currently, the majority of these patients do undergo angiography (invasive or, less often, computed tomography coronary angiography) to define anatomy and treatment options. However, given the lack of clear data demonstrating benefit of revascularization in stable CAD patients, it is logical to ascertain if medical therapy without catheterization is an appropriate approach. ISCHEMIA is currently enrolling subjects and will be an important study to determine the optimal diagnostic approach to subjects with stable angina. It will be interesting to see if the interaction between symptoms and ischemia as reported by Steg et al. is reproduced in ISCHEMIA.

Equipoise ethics

equipoise ethics


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