Good in one situation but not in another

In September 2009, the New England Journal of Medicine informed its readers that the RE-LY study showed evidence of the thrombin inhibitor Dabigatran being as effective as, if not better than, Warfarin for the prevention of thromboembolic events in patients with atrial fibrillation. Those patients with atrial fibrillation who took Dabigatran in a dose of 110 mg twice daily had the same rates of stroke as those who took Warfarin but had significantly lower rates of major hemorrhage. Those patients who took Dabigatran in a higher dose of 150 mg twice daily had the same rates of major hemorrhage as Warfarin but with lower rates of stroke. So, either way, we see a benefit of Dabigatran over Warfarin.

Can we conclude that Dabigatran is at least as good as Warfarin in preventing undesired thrombosis and thromboembolic phenomena in the body?

The RE-ALIGN study published in the New England Journal of Medicine in September 2013 tells us that we cannot make that generalisation. It appears that a drug that is good in one situation is not necessarily good in all situations. In this RE-ALIGN study, the investigators report that Dabigatran was not as effective as Warfarin in preventing thromboembolic complications in patients who had mechanical heart valves. Furthermore, it was associated with an increased risk of bleeding. The message they send us is: use Warfarin, not Dabigatran, for preventing thromboembolism in patients with mechanical heart valves.

What is the reason for this paradox? The authors of the RE-ALIGN study tell us that this could be because the mechanisms involved in the clotting of blood are different in atrial fibrillation and in mechanical heart valves. Stasis of blood in the atria is the cause of thrombosis in atrial fibrillation while contact of blood with the mechanical valve and the release of tissue factor after surgery are the mechanisms of thrombosis in those with mechanical heart valves. These differences make Dabigatran good in one situation but not in the other. This reminds me of something else which is good in one situation but not not in another: the combination of aspirin and clopidogrel is good in acute coronary syndromes but not in chronic stable angina.