Doctors fail to follow advice in giving tPA

BMJ 2000; 320 doi: (Published 11 March 2000) Cite this as: BMJ 2000;320:666
  1. Scott Gottlieb
  1. New York

    When given by experienced doctors, tissue-type plasminogen activator (tPA), a drug known mostly for treatment of heart attacks, can improve the recovery of patients who have had strokes, according to a new study.

    But doctors prescribing tPA often err by giving it to patients without proper indications for the treatment or by failing to give the drug at the right time.

    In the first of two studies, researchers looked at treatment for 3948 stroke patients admitted to hospitals in Cleveland, Ohio, from July 1997 to June 1998. Of these, only 70 patients received tPA, partly because it is regarded as helpful only if patients get it within three hours of experiencing a stroke (JAMA 2000;283:1151-8).

    The researchers found that tPA was associated with in-patient mortality of 15.7% more than three times the death rate among stroke patients who did not receive the drug. The in-patient mortality in the patients who received tPA was also nearly double the 7.9% expected death rate based on the severity of the patients' illness.

    These researchers also found, however, that in about a third of cases, doctors violated the treatment rules for using tPA, often giving it after the three hour limit and when patients had already taken anticoagulants.

    The second, contrasting study was conducted at Stanford University Medical Center, California, and at 23 other academic hospitals and 33 community hospitals throughout the United States. It showed a much lower rate of symptomatic cerebral haemorrhages—only 3% of 389 stroke patients given tPA experienced such haemorrhages (JAMA 2000;283:1145-50).

    The Stanford study differed from the Cleveland study in that the Stanford doctors knew that they were being scrutinised and had previous experience in the use of tPA—and in knowing which patients should not receive the drug according to accepted guidelines. In the Cleveland study, in half of the cases, treatment with tPA involved deviation from treatment guidelines compared with a third of the cases in the Stanford study.

    The findings of these two studies create a dilemma for doctors treating patients with stroke. tPA is known to lower, by about 13% the rate of lingering dis-ability, including dysarthria and weakness; but to be effective, tPA must be administered within three hours of the first symptom of a stroke to reduce the chance of further brain damage.

    “I think the findings should be … a wake up call to physicians that we need to treat patients sooner in the emergency room,” said Gregory Albers, lead author of the second study and a physician with the Stanford Stroke Center at Stanford University, Palo Alto.

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