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Cardiogenic shock after myocardial infarction is often lethal. The urgent search for better treatments led scientists to the nitric oxide pathway, which is activated during a heart attack and causes vasodilation and myocardial depression. Preventing the release of nitric oxide by inhibiting the enzyme responsible, nitric oxide synthetase, did not produce the expected survival benefit in a recent placebo controlled trial, however.
The drug tilarginine was so clearly ineffective that researchers stopped recruiting early on the grounds that continuing the study was futile. Patients given the drug were just as likely to die within a month (48%, 97/201) as those given a placebo (42%, 76/180). Tilarginine had no discernible effect on longer term mortality (six months), and it didn't help speed up the resolution of heart failure.
Perhaps the drug failed because it disabled all three isoforms of the enzyme, not just the most harmful one, writes one commentator (pp 1711-3). Or perhaps we simply don't know enough about the nitric oxide pathway to predict reliably what will happen when we inhibit it. But for now it seems clear that non-selective inhibition of nitric oxide synthetase should not be attempted in patients with cardiogenic shock complicating acute myocardial infarction.