Reperfusion therapy for acute myocardial infarction. Which strategy for which patient?
Several modes of reperfusion therapy for evolving myocardial infarction (MI) have been developed, which differ in terms of effectiveness, complexity and costs. Reperfusion resources are often restricted by budgetary or logistical circumstances. To arrive at an equitable distribution of treatment options, physicians should therefore consider which treatment to apply in which patient. Two major questions which arise in this respect are discussed here: what is the treatment effect in an individual patients, and what is an equitable resource allocation? Currently, the most relevant treatment options are: streptokinase (1.5MU over 1h), reteplase (2 boluses of 10MU), alteplase (tissue plasminogen activator; t-PA) [100mg over 1.5 hours] and immediate angioplasty. In combination with aspirin, streptokinase leads to an almost 40% mortality reduction at 1 month compared with placebo [from 13.2 to 8.0%; Second International Study of Infarct Survival (ISIS-2) trial]. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-1) study demonstrated a further mortality reduction by early combination therapy of aspirin, intravenous heparin and alteplase vs aspirin, heparin (either intravenous or subcutaneous) plus streptokinase (from 7.3 to 6.3%). The clinical effects of reteplase fall somewhere between those of streptokinase and alteplase. Combined analysis of the angioplasty trials suggests that angioplasty is superior to thrombolysis, especially in patients with a high cerebral bleeding risk. The noticed gradient of efficacy runs parallel to a gradient of costs and complexity: streptokinase is the least costly treatment option while direct angioplasty is the most expensive and complex. Subgroup analyses indicate that there are neither apparent deviations in the relative effect of reperfusion therapy as compared to control treatment, nor in the additional effect of more intensive therapy (alteplase) upon 'standard' therapy (streptokinase). Consequently, the absolute number of deaths avoided by reperfusion therapy appears to be greatest in those groups with a high mortality risk without therapy. There is one major exception: in patients treated early after symptom onset a much greater relative mortality reduction is observed than in those treated later. Owing to the higher mortality risk, the life expectancy of a patient with MI is shorter than that of an 'average' person of the same community and the same age. Since mortality reduction of reperfusion therapy is maintained at long term follow-up, part of this potential loss can be regained. This 're-gain of lost years' is judged to be the ultimate treatment effect in an individual patient. An equitable treatment allocation should be such that patients who will benefit most will receive the most effective therapy, while patients with similar expected benefit will be offered the same mode of therapy. The conclusion is that treatment guidelines or protocols can be very useful in clinical practice, especially if rapid decision making is of vital importance.
University Hospital Rotterdam-Dijkzigt, The Netherlands.
E
E
Boersma
E W
EW
Steyerberg
M J
MJ
Van der Vlugt
M L
ML
Simoons
D017130:Angioplasty; D001241:Aspirin / Q000627:therapeutic use; D003365:Costs and Cost Analysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000009:adverse effects / Q000191:economics; D018570:Risk Assessment; D013300:Streptokinase / Q000627:therapeutic use; D013997:Time Factors
D005343:Fibrinolytic Agents; D013300:Streptokinase; D001241:Aspirin