Review: Aspirin, heparin and β-blockers are effective adjuvants to thrombolysis after myocardial infarction
ACP J Club. 1991 Nov-Dec;115:69. doi:10.7326/ACPJC-1991-115-3-069
Popma JJ, Topol EJ. Adjuncts to thrombolysis for myocardial reperfusion. Ann Intern Med. 1991 Jul 1;115:34-44.
To review the effectiveness of adjunctive pharmacologic agents for acute myocardial infarction.
MEDLINE (January 1985 to December 1990) was searched for relevant articles. Bibliographies of these articles were searched for further studies.
Peer-reviewed studies that evaluated the role of pharmacologic adjuncts to thrombolytic therapy for patients with acute myocardial infarction were selected.
Data were extracted on types of adjunctive agents directed at the infarct-related artery (e.g., platelet antagonists, thrombin inhibitors and other anticoagulants), and therapies directed at the myocardium (e.g., β-blockade, angiotensin-converting enzyme inhibitors, calcium channel blockade, and nitrates) and their effects on patency, recurrent ischemia, bleeding, left ventricular function, and mortality.
Aspirin: In the Second International Study of Infarct Survival (ISIS-2), oral aspirin (160 mg at presentation) reduced 6-week vascular mortality by 23% as a single agent, and by 42% in combination with streptokinase (P < 0.001). Heparin and tissue plasminogen activator (t-PA): A 10 000-U bolus of intravenous heparin did not increase coronary patency 90 minutes after treatment with t-PA in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI)-3 trial (79% for both groups). Continuous intravenous heparin after t-PA and 80 mg of aspirin, however, improved patency at 18 hours in the Heparin-Aspirin Reperfusion Trial (HART) (82% vs 52%, P< 0.001). Continuation of heparin for 7 days was no better than 24 hours of heparin for 7-day patency rates (80%) for both groups in an Australian trial. Heparin and streptokinase: Mortality in the Studio Sullas Calciparina Nell' Angina e Nella Thrombosi Ventricolare Nell' Infarto (SCATI) trial was reduced by immediate treatment with heparin (12 500 U subcutaneously, twice daily) and streptokinase, when compared with streptokinase alone (5% vs 9%, P = 0.05). The Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardio (GISSI-2) trial of subcutaneous heparin (12 hours after administration of streptokinase or t-PA) found no differences in early mortality or left ventricular function. β -blockading agents: In the Thombolysis in Myocardial Infarction Investigation (TIMI-2), early intravenous administration of metoprolol, compared with delayed metoprolol, resulted in decreased incidence of reinfarction (P = 0.02) and recurrent ischemia (P < 0.01) in patients receiving t-PA. Other therapies: Insufficient data from clinical trials are available.
Aspirin, ≥ 160 mg/d, administered early after thrombolytic therapy improves survival. Intravenous heparin begun early and continued for 24 hours improves infarct vessel patency after t-PA and may also be beneficial after streptokinase. Early β-blockade in the absence of contraindications is beneficial.
Source of funding: Not stated.
Address for article reprint: Dr. E.J. Topol, Department of Cardiology, One Clinic Center, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Thrombolysis for myocardial infarction is little more than a decade old, and attention has only recently returned to adjunctive therapy. This review emphasizes pathophysiology; others emphasize meta-analysis (1) or the consensus of experts (2).
Adjunctive drugs aimed at enhancing or maintaining patency of the infarct-related artery appear to improve outcome after thrombolysis. It is difficult, however, to use clinical trial data to determine the optimal regimen of thrombolytics, antiplatelet agents, and anticoagulants, because these drugs have complex interactions and can be combined in hundreds of possible regimens. The data clearly support use of aspirin, which is inexpensive and simple to administer. The authors' recommendations for use of heparin are reasonable but rely on data that are inconsistent and difficult to interpret because of differences among studies in end points, dosing regimens, and concomitant therapy.
Therapy aimed at the ischemic myocardium was used before thrombolysis became accepted therapy, and the issue is how to interpret evidence from the prethrombolytic era. I think it is reasonable to extrapolate previous experience, but some direct evidence of efficacy in the presence of thrombolysis is reassuring. β-blockers were shown in several large trials in the prethrombolytic era to improve mortality after myocardial infarction; the TIMI-2 data suggest that the evidence from older studies for early β-blocker administration can be extended to patients given thrombolytic agents. There are no trials of nitrates, calcium blockers, or anti-arrhythmics in the setting of thrombolysis, but there is also no clear reason to change interpretation of previous data concerning their efficacy.
Mark A. Hlatky, MD
Stanford UniversityStanford, California, USA
1. Yusuf S, Sleight P, Held P, McMahon S. Routine medical management of acute myocardial infarction. Lessons from overviews of recent randomized controlled trials. Circulation. 1990;82(Suppl 2):117-34.