Age related outcome in acute myocardial infarction

Elderly people benefit from thrombolysis and should be included in trials

Patients older than 70 account for a third to a half of patients with acute myocardial infarction admitted to hospital,1 and 80% of deaths due to acute myocardial infarction occur in those aged over 65 years, 60% of them in people aged 75 or more.2 Despite extensive studies of thrombolytic treatments in large numbers of patients, we lack data on elderly subjects over 75 and particularly among those over 85. The size of the elderly population is growing: between 1982 and 1992 the Nottingham heart attack register recorded a 70% increase in patients aged 70-74 admitted with myocardial infarction anda 200% increase in those aged 75 or over.3 Hence we must be able to assess the optimal therapeutic strategies for such patients.

The application of trial results to clinical practice is hampered by the fact that such patients, although accounting for up to half of cases of myocardial infarction and having a disproportionately high mortality, are significantly underrepresented in clinical trials. Over 60% of trials have excluded patients aged over 75, with higher rates of exclusion in studies involving invasive procedures.2 An overview of thrombolytic trials showed that only 10% of patients were aged over 74.4

Older patients have a higher incidence of previous myocardial infarction, heart failure, cardiogenic shock, atrioventricular block, and atrial fibrillation or flutter.5 In the angiographic substudy of GUSTO-1, older subjects had higher rates of TIMI grade 0 flow and lower rates of TIMI grade 3 flow, more multivessel disease, and lower left ventricular ejection fractions.5 Thus it is not surprising that studies that have included older people have shown higher mortality with treatment than have trials in younger patients. For example, the Fibrinolytic Therapy Trialists' Collaborative Group showed 35 day mortality for thrombolytic treated patients of 3.4%, 7.2%, 13.5%, and 24.3% respectively for people aged <55, 55-64, 65-74, and ≥75.6 In the GUSTO-1 study patients aged over 75 treated with alteplase had a 30 day mortality of 19% (250/1297) and streptokinase treated patients a mortality of 21% (486/2358) compared with 4.4% (398/9039) and 5.5% (979/17 804) respectively for those aged 75 and under.7 A recent French study showed a relative risk of 4.65 for five day mortality among those aged over 80 years (compared with those aged 50 and under).8

An overview of large trials showed no significant differences in the proportional mortality reductions achieved by thrombolytic therapy between different subgroups, so the absolute reduction in deaths is greater among those, such as elderly people, with a higher mortality.9 In addition to reductions in hospital and short term mortality for elderly subjects, there is evidence of long term benefit: the four year follow up of ISIS-2 showed survival benefits of streptokinase treatment for at least four years, irrespective of age.10 The benefits of thrombolytic therapy in the elderly are also cost effective.11

The increased incidence of adverse events with increasing age, particularly intracerebral haemorrhage, has inhibited widespread use of thrombolytic treatment among elderly patients. In the GUSTO-1 trial the incidence of intracerebral haemorrhage among patients aged over 75 was 2.08% in those treated with alteplase and 1.23% in those treated with streptokinase compared with 0.52% and 0.42% respectively among patients aged 75 and under.7 In selecting elderly patients for thrombolytic therapy, clinicians need to take account of other factors that increase the risk of intracerebral haemorrhage: hypertension, low body weight, oral anticoagulants before admission, female sex (even after adjustment for worse baseline characteristics), and history of cerebrovascular disease.

Even in the absence of specific contraindications older patients still receive thrombolytic treatment less often than younger ones.4Although the incidence of stroke is higher in elderly people, the greater overall mortality reduction with thrombolytic treatment may result in greater net clinical benefits. The alternative strategy of primary angioplasty to avoid the increased bleeding risk of thrombolytic therapy cannot be recommended in view of the lack of data on primary angioplasty in patients over 75 years.

The lack of data on elderly patients is particularly pronounced in those over 85 years, who are increasingly encountered in clinical practice. The COBALT study population of 7169 patients included 96 over 85 years, who had a remarkably high 30 day mortality (31% v 7.4% for those ≤ 85 years).12

Age is the most important predictor of survival after acute myocardial infarction. Most of the available data support the use of thrombolytic treatment in elderly patients with acute myocardial infarction. While a slightly higher rate of adverse events, particularly intracerebral haemorrhage, may be expected, overall more lives will be saved and mortality benefits maintained for several years. Despite this evidence, advanced age remains one of the strongest predictors for not receiving thrombolytic therapy. To enable clinicians to make informed decisions about the use of thrombolytic treatment in their elderly patients, particularly the very elderly, future trials of thrombolytic therapy should avoid age related exclusion criteria.