Current issues of ACP Journal Club are published in Annals of Internal Medicine


rt-PA given within 5 hours after myocardial infarction reduced total analgesic needs

ACP J Club. 1991 July-Aug;115:15. doi:10.7326/ACPJC-1991-115-1-015

Source Citation

Kristensen KS, Haarbo J, Munkvad S, Stoltenberg M. Early thrombolytic treatment reduces analgesic requirement in patients with myocardial infarction. J Intern Med. 1991 Mar;229:257-9.



To investigate the effect of early thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) on the analgesic needs of patients with myocardial infarction.


Substudy of the randomized, double-blind, placebo-controlled trial of early thrombolytic therapy (Anglo-Scandinavian Study of Early Thrombolysis-ASSET), with analgesics given as needed. Analgesic requirements were assessed during the first 48 hours of thrombolytic therapy.


4 Danish centers.


76 of 129 patients < 76 years of age (range, 37 to 75 y) with suspected myocardial infarction of < 5 hours duration had the infarction confirmed by enzymatic or electrocardiographic changes (or both) and were permitted analgesics on demand. Patients who were prescribed intravenous nitroglycerine, β-blockers, or naloxone were excluded. 3 patients randomized to rt-PA and 6 randomized to placebo were excluded because they required nitroglycerine. Of 67 patients, 43 were men.


Patients were treated with 100 mg of intravenous rt-PA (n = 30) or placebo (n = 37) within 5 hours of the myocardial infarction. All patients received intravenously injected heparin, 5000 IU, followed by an infusion of 1000 IU/h for 21 hours. Analgesics (morphinomimetics or levomepromazine, with dosage converted into equivalents of mg of morphine) were given at the patient's request or when the nurses observed the patient to be in pain.

Main outcome measure

Total analgesic requirements during the 48-hour period after starting thrombolysis or placebo.

Main results

Patients assigned to rt-PA required a median of 5.3 mg of morphine (range, 0 to 45 mg) in 48 hours, compared with a median of 11.2 mg (range, 0 to 115 mg) for the placebo group (P = 0.04). 20 of 30 patients (67%) receiving rt-PA did not require analgesics for > 6 hours compared with 14 of 37 patients (38%) assigned to placebo (P = 0.04). {This absolute risk improvement of 28% means that 3 patients would need to be treated with rt-PA (compared with placebo) to have 1 additional patient not require analgesics for > 6 hours, 95% CI 2 to 21, the relative risk improvement was 76%, CI 10% to 192%}.*


Administration of rt-PA within 5 hours after myocardial infarction reduced the total analgesic requirements of patients in the next 48 hours. Compared with a control group, fewer patients on the rt-PA regimen required analgesia for more than 6 hours.

Source of funding: Not stated.

Address for article reprint: Dr. K.S. Kristensen, Department of Pharmacology, University of Copenhagen, 20 Juliane Mariesvej, DK, 2100 Copenhagen, Denmark.

*Numbers calculated from data in article.


There is unequivocal evidence that thrombolytic therapy for acute myocardial infarction recanalizes occluded coronary arteries, preserves left ventricular function, and reduces mortality (1).

The authors of this substudy have shown that the early use of rt-PA reduces the requirements for analgesia within the first 48 hours. The blinded nature of the study should have minimized biases in the administration of analgesia. Although the total amount and duration of analgesia were lower with rt-PA after the start of therapy, no data were provided on the analgesic requirements from time of presentation to the onset of thrombolysis. It is possible that early imbalances in the use of analgesics may have accounted for these results. Patients excluded were those receiving either β-blockers or intravenous nitrates, preventing their potential confounding effects on the pain of acute myocardial infarction.

The implication of these results is that thrombolysis reduces the pain of acute myocardial infarction, probably (but not certainly) caused by reperfusion. A comparison of several different thrombolytic agents might give indirect evidence for this hypothesis because different agents produce differing velocities of reperfusion, although patency rates appear to be similar at 24 hours.

These results are based on the differences between group medians, but the overall care of the individual patient with a suspected acute myocardial infarction need not differ because of the use of thrombolytic agents. It is important that physicians not get caught up in the excitement of using these extremely effective agents and inadvertently forget the other essential aspects of the management and care of the patient, including pain control.

David Massell, MD
Hamilton General HospitalHamilton, Ontario, Canada


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 3):II-117-34.