DEATH OR DISABILITY?

It’s not just aspirin which has come under fire recently. Other standard treatments such as thrombolysis are also being questioned after trials revealed a higher death rate. When thrombolysis is used after cerebral infarction the likely result is another stroke this time caused by cerebral hemorrhage. Heparin and warfarin are both indicated in increased incidence of cerebral hemorrhage, but the most recent debate has been over the use of agents such as streptokinaise (SK) and recombinent tissue plasminogen activator (rtPA).

Three large SK trials have been terminated because of early high mortality due to intracerebral hemorrhage. One trial for rtPA also showed increased mortality. In none of these four trials was there any benefit for subsequent disability that could offset the excess early mortality (Lancet, 1996; 347:391). Thrombolysis is a high risk strategy in stroke, especially if administered “late” (three to six hours after the stroke). The National Institutes of Neurological Disorders and Stroke (NINDS) trial showed an even smaller “therapeutic window” (under three hours) for the administration of rtPA (N J Med, 1995; 333:1581-7).The MAST-I trial (Lancet, 1995; 346:1509-14) was abandoned when high death rates were revealed amongst those receiving these drugs. Mortality was increased from 24.3 per cent to 35.8 per cent in the first six months, though disability over the longer term decreased from

53.4 per cent to 41.8 per cent. Commentary on the trial asked, among other things, whether it was ethical to ask patients whether they would rather be dead or disabled. (Lancet, 1995; 347:391-3). The MAST-I results were not unique (Circulation, 1995; 92:2811-8; NE J Med, 1995; 335: 1581-7; NE J Med, 1996; 336:145-60).

Different thrombolitic drugs given in different ways may have different effects (JAMA, 1995; 274:1017-25) and it is the elderly (in other words, the majority of stroke patients) who are more likely to experience cerebral hemorrhage and have a higher mortality rate (Circulation, 1995; 92:2811-8).