Myocardial Infarction

• Introduction

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• ST Elevation Infarction
• Thrombolytic Therapy- Reducing Mortality
• Thrombolytic Therapy- Additional Benefits

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• Assessing Extent of Infarction
• ECG and Q Waves

Thrombolytic Therapy for ST-segment Elevation Myocardial Infarction

Reducing Mortality Rates

Numerous large "mega-trials" were done to assess the risks and benefits of thrombolytic therapy. This brief review will selectively mention the findings of two of the many landmark trials.

One of the earliest trials was conducted by the GISSI group: In this study those patients having a myocardial infarct were treated with streptokinase, a thrombolytic agent. The trial found that:

• those with ST depression did worse if given thrombolytic therapy
• the streptokinase (SK) group had a 17.2% mortality rate at one yr compared with a 19% mortality rate for the placebo group; a 10% reduction
• those that received SK early (<1 hour) had a 40% reduction in mortality
• those that received SK <3 hours had a 13% reduction in mortality
• those that received SK between 3 and 6 hours also had a 13% mortality reduction
• those that had SK after 6 hours did not seem to benefit from therapy

Mortality rates at one year were higher in older patients:

• <65 years- 10-12%
• 65-75year- 25%
• >75 years- 40%

Mortality rates at one year were higher in men:

• men: 30%
• women: 15%

These "overall" findings may not represent the prognosis of an individual patient. For example, although the mortality rate was high in those over the age of 75 years, even within this group there will be some that will have a better prognosis, and others that will have a worse prognosis.

In this study multivariate analysis seemed to indicate, that in terms of mortality benefit at one year, only those older than 65 years and men obtained benefit from Streptokinase therapy. Many studies may not show benefit in lower risk groups because of lack of statistical power. In addition, lower risk groups may not show benefit at one year but medium term studies might be expected to show benefit.

Further analysis showed that one year mortality was reduced only if the patient had no previous infarct or the infarct in question was located anteriorly.

At six month followup:

• reinfarction was slightly more common in SK group- 3.6% vs 2.5%
• rates of angina, heart failure and stroke were the same in both groups
• the rates of CABG (2.8%-3.0%) and angioplasty (0.2%-0.3%) were low and not different between groups.

Much has changed since this study was published, in terms of improvements in percutaneous therapy and in bypass surgery; as well as improvements in pharmacological therapy. Mortality rates today should be less than shown in this early trial.

The GUSTO I trial compared, in patients with ST-elevation infarction, intravenous streptokinase with subcutaneous heparin or intravenous heparin, tPA with intravenous heparin or a combination of streptokinase with tPA.

The study showed a slight advantage with tPA. Subgroup analysis suggested that the benefit was limited to those aged less than 75 years, to those with anterior infarcts and to those treated within four hours. Given the markedly greater cost with tPA this agent did not replace streptokinase therapy for all patients- most centers used tPA selectively.

Other studies investigated newer thrombolytic agents or adjunctive agents, but to date there have been few major advances in treatment with these agents. One of the problems with use of thrombolytic therapy has been the small but significant risk of bleeding, including intracranial bleeding..

References:

• Long term effects of intravenous thrombolysis in acute myocardial infarction:final report of the GISSI study, Lancet 1987;Oct:871-874
  
• An international randomised trial comparing four thrombolytic strategies for acute myocardial infarction N Eng J Med 1993;329:673-82