Thrombolysis for Acute Myocardial Infarction: Drug Review

David K. Cundiff

Disclosures
In This Article

Abstract and Introduction

The proof of efficacy of thrombolysis for acute myocardial infarction (AMI) depends on 9 randomized placebo-controlled trials totaling 58,511 patients. The meta-analysis of these trials showed an overall survival advantage of about 2% (11.5% vs 9.6%) in favor of thrombolysis. Iatrogenic deaths from thrombolysis complications occur in about 1% of AMI patients. Timely opening of the infarct-related artery (IRA) allowing myocardial reperfusion has been proposed to explain any survival advantage seen with thrombolysis ("open-artery hypothesis"). Angiographic data does not support the open-artery hypothesis as the mechanism of any benefit of thrombolysis. The "early hazard" (ie, increased mortality in the first 12 hours after thrombolysis) also suggests that the supposed survival benefit is due to something other than early reperfusion. The variable use of aspirin in the meta-analysis trials may have confounded the results and conclusions. In the 4 studies of the meta-analysis in which aspirin was used routinely (n = 21,144), the survival benefit was not statistically significant (P = .14). Lack of blinding in some studies and other methodologic problems may also call the conclusions of the meta-analysis into question. AMI registry reports comparing patients with and without thrombolysis have not borne out a significant survival advantage with thrombolysis. The National Registry of Myocardial Infarction (NRMI) registry data suggest that a significant number of AMI patients may be inappropriately receiving thrombolytics. An independent analysis of the NRMI mortality data adjusted for age and other risk factors would help determine whether thrombolysis for AMI improves survival.

Current American College of Cardiology/American Heart Association guidelines recommend that thrombolytic therapy be administered to all patients regardless of age, sex, or race who have symptoms suggestive of a myocardial infarction and who present to the hospital within 12 hours of symptom onset, have diagnostic changes on their 12-lead electrocardiogram (ie, ST-segment elevation or left bundle-branch block), and have no contraindications to thrombolytic therapy.[1,2]

To evaluate the theoretical and scientific basis of this guideline, this paper will:

  1. Analyze the "open-artery hypothesis" that early patency after acute coronary artery thrombosis improves survival;

  2. Critique the randomized clinical trials that purport to prove the efficacy of thrombolysis in AMI;

  3. Examine the subsequent treatment and outcome data from registries of AMI patients; and

  4. Review the risks and costs of thrombolytic therapy.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....