Comparative Tolerability Profiles of Thrombolytic Agents

Abstract

The 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required.

In vitro Thrombolytic and Membrane Stabilizing Studies of Brassica rapa subsp. chinensis (L.) Hanelt

“…are used all over the world but still associated with risk of hemorrhage, anaphylactic reaction and lack specificity. So, attempts are still ongoing around the world to develop improved thrombolytic agents (Hilleman and Campbell, 2011;Tsikouris and Tsikouris, 2001;van Domburg et al, 2000;Woo and White, 1993). With this view, this investigation was done on B. rapa subsp.…”

Successful treatment of a catheter-related right atrial thrombosis with recombinant tissue plasminogen activator and heparin

“…Three thrombolytic agents are currently used for arterial and venous thrombo-embolic events: streptokinase, urokinase and rhtPA. Urokinase and rh-tPA are more common, basically because they carry a lower incidence of non-hemorrhagic adverse effects, such as hypotension, allergy and antibody formation [9]. There are fewer reports on the use of tissue plasminogen activator than on urokinase, but the former offers some potential advantages over the other two thrombolytic agents: (1) it is not immunogenic because it is obtained by the DNA recombination technique and has the same properties as the human endothelial glycoprotein; (2) it has a high affinity for fibrin, causing fibrinolysis without activating systemic proteolysis; (3) it has a low affinity for circulating plasminogen and its short half-life reduces the risk of bleeding.…”

Thrombolytic Therapy: A Review of Its Use in Acute Myocardial Infarction

“…87 The risk for severe adverse effects, such as a cerebral hemorrhage, systemic bleeding that results in the need for a major transfusion, severe hypotension, and allergic reactions, is relatively low. 88 Results from large comparative trials best reflect any variation in the incidence of these adverse effects among agents. These results, however, need to be evaluated carefully, since differences in the inclusion/exclusion criteria, concomitant adjunctive agents used, and/or the criteria that define an adverse event may differ in each trial.…”

“…92 Hypotension has also been attributed to the use of thrombolytic therapy. 88 It is theorized that increasing serum plasmin concentrations activate kal-likrein and stimulate bradykinin production, leading to vasodilation. 93 Anistreplase and streptokinase appear to be implicated more frequently than is alteplase or reteplase.…”

“…29 Stimulation of immunoglobulin E antibodies by streptokinase or anistreplase can result in immediate allergic reactions. 88 These reactions may range from a mild presentation, such as fever, urticaria, myalgia, flushing, and chills, to a more severe episode such as anaphylactic shock. The overall incidence of these allergic reactions is remarkably low for streptokinase and anistreplase, and is even lower for alteplase and reteplase.…”