Platelet Reactivity and Streptokinase Resistance following Antecedent Streptokinase Therapy for Myocardial Infarction

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Abstract

Aims: To assess the efficacy of second-time administration of streptokinase (SK). First-time thrombolysis with SK in myocardial infarction (MI) is established but the efficacy of subsequent SK is unknown. Methods and Results: Platelet reactivity to shear stress, spontaneous and SK-induced thrombolysis were measured in vitro in 28 patients who had received SK for MI and compared to 15 controls. SK antibody (Ab) titres were inversely related to time from MI. Platelet reactivity was greatly enhanced in patients (p < 0.0001). Spontaneous thrombolysis in patients was poor and in 17 failed to occur. In contrast, thrombolysis occurred in all but 1 control. In patients platelet reactivity was strongly related to thrombolytic activity (r = –0.516; p = 0.0029). SK in vitro was at least 4 times more effective in controls than in patients. Conclusion: The chances of achieving patency with second administration of SK are poor. Ab titre is not a reliable predictor of resistance.

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Most cited references 4

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Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour.

J. W. Deckers, M Simoons, C Maas … (1996)

There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment. The relation between treatment delay and short-term mortality (up to 35 days) was evaluated using tabulated data from all randomised trials of at least 100 patients (n = 22; 50,246 patients) that compared fibrinolytic therapy with placebo or control, reported between 1983 and 1993. Benefit of fibrinolytic therapy was 65 (SD 14), 37 (9), 26 (6) and 29 (5) lives saved per 1000 treated patients in the 0-1, 1-2, 2-3, and 3-6 h intervals, respectively. Proportional mortality reduction was significantly higher in patients treated within 2 h compared to those treated later (44% [95% CI 32, 53] vs 20% [15, 25]; p = 0.001). The relation between treatment delay and mortality reduction per 1000 treated patients was expressed significantly better by a non-linear (19.4-0.6x(+)29.3x-1) than a linear (34.7 - 1.6x) regression equation (p = 0.03). The beneficial effect of fibrinolytic therapy is substantially higher in patients presenting within 2 h after symptom onset compared to those presenting later.

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Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease.

Mark I. Furman, Stephen E Benoit, Marc R. Barnard … (1998)

We sought to examine whether patients with stable coronary artery disease (CAD) have increased platelet reactivity and an enhanced propensity to form monocyte-platelet aggregates. Platelet-dependent thrombosis and leukocyte infiltration into the vessel wall are characteristic cellular events seen in atherosclerosis. Anticoagulated peripheral venous blood from 19 patients with stable CAD and 19 normal control subjects was incubated with or without various platelet agonists and analyzed by whole blood flow cytometry. Circulating degranulated platelets were increased in patients with CAD compared with control subjects (mean [+/- SEM] percent P-selectin-positive platelets: 2.1 +/- 0.2 vs. 1.5 +/- 0.2, p < 0.01) and were more reactive to stimulation with 1 micromol/liter of adenosine diphosphate (ADP) (28.7 +/- 3.9 vs. 16.1 +/- 2.2, p < 0.01), 1 micromol/liter of ADP/epinephrine (51.4 +/- 4.6 vs. 37.5 +/- 3.8, p < 0.05) or 5 micromol/liter of thrombin receptor agonist peptide (TRAP) (65.7 +/- 6.8 vs. 20.2 +/- 5.1, p < 0.01). Patients with stable CAD also had increased circulating monocyte-platelet aggregates compared with control subjects (percent platelet-positive monocytes: 15.3 +/- 3.0 vs. 6.3 +/- 0.9, p < 0.01). Furthermore, patients with stable CAD formed more monocyte-platelet aggregates than did control subjects when their whole blood was stimulated with 1 micromol/liter of ADP (50.4 +/- 4.5 vs. 28.1 +/- 5.3, p < 0.01), 1 micromol/liter of ADP/epinephrine (60.7 +/- 4.3 vs. 48.0 +/- 4.8, p < 0.05) or 5 micromol/liter of TRAP (67.6 +/- 5.7 vs. 34.3 +/- 7.0, p < 0.01). Patients with stable CAD have circulating activated platelets, circulating monocyte-platelet aggregates, increased platelet reactivity and an increased propensity to form monocyte-platelet aggregates.

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Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

Doug Armstrong, Christopher P. Nelson, R Califf … (1995)

Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

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Journal ID (publisher-id): CRD

Journal ID (nlm-ta): Cardiology

Journal ID (doi): 10.1159/issn.0008-6312

Title: Cardiology

Publisher: S. Karger AG

ISSN (Print): 0008-6312

ISSN (Electronic): 1421-9751

Publication date Subscription-year: 1999

Publication date (Print): June 1999

Publication date (Electronic): 18 June 1999

Volume: 91

Issue: 1

Pages: 56-59

Affiliations

Division of Cardiology, Imperial College School of Medicine, Hammersmith Hospital, London, UK

Article

Publisher ID: 6877 Other ID: Cardiology 1999;91:56–59

DOI: 10.1159/000006877

PubMed ID: 10393399

SO-VID: e6adadc1-8b7a-42c5-97b8-208df6b7e6db

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Platelet Reactivity and Streptokinase Resistance following Antecedent Streptokinase Therapy for Myocardial Infarction

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Karger: Cardiovascular System

Most cited references 4

Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour.

Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease.

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

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