Weight-adjusted dosing of TNK-tissue plasminogen activator and its relation to angiographic outcomes in the thrombolysis in myocardial infarction 10B trial

C. Michael Gibson, Christopher P. Cannon, Sabina A. Murphy, A. A Jennifer Adgey, Marc J. Schweiger, Rafael F. Sequeira, Gilles Grollier, Norma Lynn Fox, Silvano Berioli, W. Douglas Weaver, Frans Van De Werf, Eugene Braunwald

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Abstract

Fixed doses of thrombolytic agents are generally administered to patients of varying body weights, and the dose-response relation may be confounded by the variability in patient weight. We hypothesized that higher doses of TNK-tissue plasminogen activator (tPA) per unit body weight would be related to improved flow at 90 minutes after thrombolytic administration. A total of 886 patients with acute myocardial infarction were randomized to receive either a single bolus of 30, 40, or 50 mg of TNK-tPA or front-loaded tPA in the Thrombolysis In Myocardial Infaction (TIMI) 10B trial. The dose of TNK-tPA administered was divided by the patient's weight to arrive at the TNK-tPA dose (mg) per unit body weight (kg), and patients were stratified into tertiles based on mg/kg of TNK-tPA: low dose, 0.2 to 0.39 mg/kg; mid- dose, 0.40 to 0.51 mg/kg; high dose, 0.52 to 1.24 mg/kg. Flow in the culprit and nonculprit arteries was analyzed using the TIMI flow grades and the corrected TIMI frame count (CTFC). The median CTFC in culprit arteries differed between the tertiles (3-way p = 0.007), with the CTFC being 7.2 frames faster in high-dose than in low-dose patients (43.1 ± 30.1, median 31.2, n = 171 vs 54.6 ± 34.8, median 38.4, n = 166, 2-way p = 0.002). Patients in the mid- and high-dose tertiles achieved patency more frequently (TIMI grade 2 or 3 flow) by 60 minutes (p = 0.02), and the 90-minute percent diameter stenosis was less severe in patients in the high-versus low-dose tertile (p = 0.03). In nonculprit arteries, the CTFC was faster in high- than in low-dose tertiles (29.6 ± 13.4, median 26.9, n = 130 vs 34.7 ± 16.3, median 32.8, n = 108, 3-way p = 0.03, 2-way p = 0.008). In patients who underwent percutaneous transluminal coronary angioplasty (PTCA), the CTFC in culprit arteries after PTCA was fastest in the high- and mid-dose tertiles than in those receiving low doses (2- way p = 0.05). Thus, higher doses per unit body weight of TNK-tPA result in not only faster culprit artery flow, but also faster nonculprit, global, and post-PTCA flow, which may reflect earlier opening, reduced stunning, or improved microvascular function. The greater effectiveness of thrombolysis must be weighed against any increase in risk.

Original languageEnglish
Pages (from-to)976-980
Number of pages5
JournalAmerican Journal of Cardiology
Volume84
Issue number9
DOIs
StatePublished - Nov 1 1999
Externally publishedYes

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Myocardial Infarction
Weights and Measures
Arteries
Coronary Balloon Angioplasty
Body Weight
TNK-tissue plasminogen activator
Fibrinolytic Agents
Tissue Plasminogen Activator
Pathologic Constriction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Weight-adjusted dosing of TNK-tissue plasminogen activator and its relation to angiographic outcomes in the thrombolysis in myocardial infarction 10B trial. / Gibson, C. Michael; Cannon, Christopher P.; Murphy, Sabina A.; Adgey, A. A Jennifer; Schweiger, Marc J.; Sequeira, Rafael F.; Grollier, Gilles; Fox, Norma Lynn; Berioli, Silvano; Weaver, W. Douglas; Van De Werf, Frans; Braunwald, Eugene.

In: American Journal of Cardiology, Vol. 84, No. 9, 01.11.1999, p. 976-980.

Research output: Contribution to journalArticle

Gibson, CM, Cannon, CP, Murphy, SA, Adgey, AAJ, Schweiger, MJ, Sequeira, RF, Grollier, G, Fox, NL, Berioli, S, Weaver, WD, Van De Werf, F & Braunwald, E 1999, 'Weight-adjusted dosing of TNK-tissue plasminogen activator and its relation to angiographic outcomes in the thrombolysis in myocardial infarction 10B trial', American Journal of Cardiology, vol. 84, no. 9, pp. 976-980. https://doi.org/10.1016/S0002-9149(99)00483-X
Gibson, C. Michael ; Cannon, Christopher P. ; Murphy, Sabina A. ; Adgey, A. A Jennifer ; Schweiger, Marc J. ; Sequeira, Rafael F. ; Grollier, Gilles ; Fox, Norma Lynn ; Berioli, Silvano ; Weaver, W. Douglas ; Van De Werf, Frans ; Braunwald, Eugene. / Weight-adjusted dosing of TNK-tissue plasminogen activator and its relation to angiographic outcomes in the thrombolysis in myocardial infarction 10B trial. In: American Journal of Cardiology. 1999 ; Vol. 84, No. 9. pp. 976-980.
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AU - Adgey, A. A Jennifer

AU - Schweiger, Marc J.

AU - Sequeira, Rafael F.

AU - Grollier, Gilles

AU - Fox, Norma Lynn

AU - Berioli, Silvano

AU - Weaver, W. Douglas

AU - Van De Werf, Frans

AU - Braunwald, Eugene

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N2 - Fixed doses of thrombolytic agents are generally administered to patients of varying body weights, and the dose-response relation may be confounded by the variability in patient weight. We hypothesized that higher doses of TNK-tissue plasminogen activator (tPA) per unit body weight would be related to improved flow at 90 minutes after thrombolytic administration. A total of 886 patients with acute myocardial infarction were randomized to receive either a single bolus of 30, 40, or 50 mg of TNK-tPA or front-loaded tPA in the Thrombolysis In Myocardial Infaction (TIMI) 10B trial. The dose of TNK-tPA administered was divided by the patient's weight to arrive at the TNK-tPA dose (mg) per unit body weight (kg), and patients were stratified into tertiles based on mg/kg of TNK-tPA: low dose, 0.2 to 0.39 mg/kg; mid- dose, 0.40 to 0.51 mg/kg; high dose, 0.52 to 1.24 mg/kg. Flow in the culprit and nonculprit arteries was analyzed using the TIMI flow grades and the corrected TIMI frame count (CTFC). The median CTFC in culprit arteries differed between the tertiles (3-way p = 0.007), with the CTFC being 7.2 frames faster in high-dose than in low-dose patients (43.1 ± 30.1, median 31.2, n = 171 vs 54.6 ± 34.8, median 38.4, n = 166, 2-way p = 0.002). Patients in the mid- and high-dose tertiles achieved patency more frequently (TIMI grade 2 or 3 flow) by 60 minutes (p = 0.02), and the 90-minute percent diameter stenosis was less severe in patients in the high-versus low-dose tertile (p = 0.03). In nonculprit arteries, the CTFC was faster in high- than in low-dose tertiles (29.6 ± 13.4, median 26.9, n = 130 vs 34.7 ± 16.3, median 32.8, n = 108, 3-way p = 0.03, 2-way p = 0.008). In patients who underwent percutaneous transluminal coronary angioplasty (PTCA), the CTFC in culprit arteries after PTCA was fastest in the high- and mid-dose tertiles than in those receiving low doses (2- way p = 0.05). Thus, higher doses per unit body weight of TNK-tPA result in not only faster culprit artery flow, but also faster nonculprit, global, and post-PTCA flow, which may reflect earlier opening, reduced stunning, or improved microvascular function. The greater effectiveness of thrombolysis must be weighed against any increase in risk.

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