Peak serum C-reactive protein concentrations were measured in 146 patients randomized to receive streptokinase, alteplase, or a combination of streptokinase and alteplase in the GUSTO-I trial. Those receiving alteplase treatment had lower values than those receiving streptokinase or the combination treatment. Irrespective of treatment, complete reperfusion of the infarct-related artery (TIMI grade 3 flow) was associated with low peak serum C-reactive protein values

Baardman, T. (Taco)

Harmoinen, A. (Aimo)

Hermens, W.T. (Wim)

Pasternack, A. (Amos)

Pietila, K.

Simoons, M.L. (Maarten)

Topol, E.J. (Eric)

Erasmus University Digital Repository

Comparison of Peak Serum C-Reactive Protein and Hydroxybutyrate Dehydrogenase Levels in Patients With Acute Aiyocardial Infarction Treated With Altepkrse and Sfreptokinuse Kari Pietib, MD, Wim T. Hermens, PhD, Aimo Harmoinen, MS, Taco Baardman, MD, Amos Pasternack, MD, Eric J. Topol, MD, and Maarten L. Simoons, MD A cute myocardial infarction (AMI) is associated with an acute-phase inflammatory reaction mea- TABLE I Patient Characteristics surable by determination of serum C-reactive pro- tein.l-5 The highest serum C-reactive protein values correlate with the size of the AM1 when thrombolytic treatment is not given.3 If reperfusion by thrombolytic treatment occurs in AMI, the serum C-reactive protein values are lower than would be expected according to infarct size.“-5 These low serum C-reactive protein values are associated with a favorable survival prog- nosis during the first 6 months after AML6 In this study we investigate the infarct-related acute-phase reaction after treatment with accelerated alteplase, streptokinase, or a combination of both. We also wanted to elucidate whether the Thrombolysis in Myocardial Infarction (TIMI) patency grade of the infarct-related artery7 was associated with this acute- phase reaction. Combined Alteplase- Alteplose Streptokinase Streptokinase (n = 48) (n = 63) (n = 32) Age (yr + SD) 592 12 61 -+ 12 60 k 11 Women (%) 9 (18%) 19 (30%) 3 (9%) Time from chest pain 3.5 i- 1.9 3.5 i- 2.2 3.5 t 4.7 onset to start of thrombolysis (hours + SD) Time from the beginning 96 i 9 972 10 97 k 9 of the treatment to angiography (minute k SD) Infarct location (%) Anterior 24 (50%) 23 (37%) 21 (66%) Inferior 22 (46%) 35 (55%) 10 (31%) Other 2 (4%) 5 (8%) 1 (3%) . . . We studied patients who had been randomized to undergo early (90 minute) coronary angiography in the Global Utilization of Streptokinase and TPA (al- teplase) for Occluded Coronary Arteries (GUSTO-I) enzyme substudy. Overall, 174 patients from the 553 patients in the enzyme substudy had been randomly assigned to angiography at the centers that also par- ticipated in the GUSTO-I angiographic substudy. Be- cause the GUSTO-I main triallo was unable to show any survival difference between the 2 streptokinase monotherapies, we chose to combine these groups. Accordingly, in this study we compared 3 treatment groups: (1) the accelerated alteplase group, (2) the streptokinase groups, and (3) the combination treat- ment group. tyrate dehydrogenase as described. l I,‘2 The size of the AM1 was determined from the cumulative release of hydroxybutyrate lactate dehydrogenase.12 In 143 of the patients all 11 blood samples were available for analysis. In 3 patients the highest serum C-reactive protein could not be determined with certainty be- cause of death within the first 2 days. These 3 patients were all in the streptokinase group and are not in- cluded in the final analyses. Coronary angiography was performed in all pa- tients 90 minutes after the start of the thrombolytic therapy. The angiographic patency of the infarct-re- lated coronary artery was graded from 0 to 3 using the TIMI classifications.7 Blood samples were available from 146 patients, 48 of whom had been treated with alteplase, 66 with streptokinase, and 32 with the combination of strep- tokinase and alteplase. Blood samples for the study were drawn at the start of thrombolytic treatment and 1, 3,5, 12, l&24, 36,48,72, and 96 hours later. They were analyzed for C-reactive protein and hydroxybu- Continuous variables were summarized in terms of means + SD and categorical variables by percentages. Multivariate analysis, the Student’s t test and chi- square test were used in statistical analyses. These were determined with the Statgraphics Plus for Win- dows (Version 2.0; Manugistics Inc., Rockville, Maryland) statistical package. . . . From the Clinic of Internal Medicine, Department of Clinical Sciences; and the Department of Clinical Chemistry, Tampere University, Tam- pere, Finland, the Cardiovascular Research Institute Maastricht, Maas- tricht, The Netherlands; Thoraxcenter, Erasmus University, Rotterdam, The Netherlands; and the Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio. This study was supported by a grant from the Finnish Heart Association, Helsinki, Finland. Dr. Pietila’s address is: Clinic of Internal Medicine, Tampere Unlversiiy Hospital, P.O. Box 2000, FIN-3352 10 Tampere, Finland Manuscript received February 4, 1997; revised manuscript received and accepted June 18, 1997 At randomization the patients in alteplase, strep- tokinase, and alteplase and streptokinase treatment groups did not differ with respect to age, delay from the onset of chest pain to the start of the treatment, time from the beginning of the treatment to angiogra- phy, or infarct location (Table I). Highest serum C-reactive protein concentrations were reached 36 to 96 hours after AMI. The serum C-reactive protein concentrations were lower overall in 01997 by Excerpta Medica, Inc. 0002.9 149/97/S 17.00 All rights reserved. PII SOOO2-9 149(97)00606-l 1075 - 3l loo- -5 c 80 - .- d ,o P 2! .- 120 - 80 - 80 - r P.NS ’ 0 24 48 72 98 Strepte Ah- Combi klnaae plasa natlon Time (hours) Treatment A B FIGURE 1. Serum C-reactive protein concentration after myocardial infarction in dif- ferent treatment grou infarction (means an B s. A, serum C-reactive protein as a function of time after the 95% confidence intervals for the means). 6, highest serum C- reactive protein concentrations [means and 95% confidence intervals for the means). The existence of significant differences between the groups was discovered by the analysis of variance method; significant differences were restudied by Student’s t test to obtain the exact p values. 1607 140- - 5 g '*O- l g IOO- 5 k 60- 3! 'S SO- f 8 40- 20- OJ PcO.05 FIGURE 2. Highest serum C-reactive protein concentrations in patients with TtMI grade 0 to 2 and TIMI grade 3 blood flow in the infarct-related coronary artery (means and 95% confidence intervals of the means). The statistical significance was calculated by Student’s t test. Open bar, TIMI 0 to 2 flow in the infarct-re- lated coronary artery. Lined bar, TJMI 3 flow in the infarct-re- lated coronary artery. the alteplase group than in the streptokinase and combi- nation treatment groups, as were the peak serum concen- trations (Figure 1). There was a tendency toward smaller infarcts in the alteplase-treated patients than in the strep- tokinase-treated patients, but the dif- ference was not statistically signifi- cant. The cumulative amounts of hy- droxybutyrate dehydrogenase released were 4.51 ? 3.17, 5.61 + 3.56, and 4.47 ? 3.92 g-l%@ in the alteplase, streptokinase, and combination treat- ment groups, respectively. The peak C-reactive protein values were lower in patients who had TIMI grade 3 perfusion in the infarct-related coronary artery than in those with TIMI grade 0 to 2 flow (Figure 2). When the patients who had TIM1 grade 0 to 2 flow were further divided into grade 2 versus grade 0 to 1 flow, the peak C-reactive protein values did not differ between these groups (82 ? 67 and 75 + 58 mg/L,). According to multivariate analysis, the peak C-reac- tive protein values of the patients who had TIMI grade 3 flow differed signif- icantly (p = 0.020) from those of pa- tients who had TIM1 grade 2 flow, whereas the difference between pa- tients who had grade 2 flow versus grade 0 to 1 flow did not quite reach statistical significance (p = 0.074). Pa- tients who had TIMI grade 3 flow had smaller enzyme release than those who had grade 0 to 2 flow (4.0 + 3.2 and 5.6 + 3.7 g-EqlL hydroxybutyrate dehydrogenase released; p = 0.008). Among patients who died during hospitalization for whom a reliable peak serum C-reactive protein concen- tration could be determined, values were higher among those who survived (143 2 122 vs 70 ? 54 mg/L; p cO.01). There were only 8 deaths in the study, however, and in only 5 of these patients was a reliable peak value of serum C-reactive protein available. . . . This study shows that treatment of AM1 with ac- celerated dosing of alteplase leads to a smaller acute- phase reaction than does streptokinase treatment alone or combination treatment with streptokinase and alte- plase. In the GUSTO-I enzyme substudy, Baardman et al* showed that treatment with alteplase led to smaller infarcts, as determined from the release of hydroxy- butyrate dehydrogenase, than did treatment with strep- tokinase. In the present subset of their patients, there was only a trend toward smaller infarcts in the alte- plase-treated patients compared with other patients. A smaller sample size.probably explains why we could not detect a significant difference. This finding is further supported by our finding that, in accordance with the main study, there was a significant associa- tion between infarct size and the TIM1 flow grade in the infarct-related artery. However, our earlier stud- ies3z5 have shown that in patients who undergo throm- bolysis for myocardial infarction, the patency of the infarct-related artery affects the serum C-reactive pro- tein values independent of its effect on infarct size. In this study, the lower peak C-reactive protein values 1076 THE AMERICAN JOURNAL OF CARDIOLOGY@ VOL. 80 OCTOBER 15, 1997 were significantly associated with complete reperfu- sion (TIM1 grade 3 flow) in the infarct-related coro- nary artery. It thus seems that the better early patency of the infarct-related artery obtained with alteplase compared with streptokinase or the combination treat- ment’3 reduces the associated acute-phase reaction. It has been shown that the patients with TIM1 grade 3 flow in the infarct-related artery have a favorable survival prognosis. 13,i4 We have shown that patients who undergo thrombolysis for AM1 and whose serum C-reactive protein values remain low have a decreased risk of death than those whose values increase over time.6 We did not specifically examine the relation of the peak serum C-reactive protein value and early mortality in this study; nevertheless, patients who died during hospitalization and in whom the peak serum C-reactive protein value could be reliably determined had higher values than those who survived. In conclusion, thrombolytic treatment of AM1 with accelerated alteplase is associated with lower peak serum C-reactive protein values than treat- ment with either streptokinase or a combination of streptokinase and alteplase. The low-peak serum C-reactive protein values were associated with complete reperfusion of the infarct-related coro- nary artery. Thus, the more efficient reperfusion with alteplase compared with the other regimensI may reduce the inflammatory reaction of AMI. Acknowledgment: The authors wish to thank the GUSTO-I Steering Committee for their review of the manuscript and Pat Williams for editorial comments. 1. de Beer FC, Hind CR, Fox KM, Allan RM, Maseri A, Pepys MB. Measure- ment of serum C-reactive protein in myocardial ischaemia and infarction. Er Heart .I 1982;41:239-243. 2. Pepys MB. C-reactive protein fifty years on. Lancer 1981;1:653-657. 3. Pietill K, Harmoinen A, PGyhb;nen L, Koskinen M, Heikkill I, Ruosteenoja R. Intravenous streptokinase treatment and serum C-reactive protein in patients with acute myocardial infarction. Br Heart J 1987;58:225-229. 4. Pietill K, Harmoinen A, Teppo AM. Acute phase reaction, infarct size and in-horpital morbidity in myocardial infarction patients treated with streptokinase or recombinant type plasminogen activator. Ann Med 1991;23:529-535. 5. Pietill K, Harmoinen A, Hermens W, Simoons ML, Van de Werf F, Verstraete M. Serum C-reactive protein and infarct size in myocardial infarct patients with a closed versus an open infarct related coronary artery after thrombolytic therapy. Eur Hem-r J 1993;14:915-919. 6. Pietill K, Harmoinen A, Jokiniitty J, Pastemack A. Serum C-reactive protein concentration in acute myocardial infarction and its relation to mortality during 24 months of follow-up in patients under thrombolytic treatment. Eur Heart J 1996; 17: 1345-l 349. 7. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen I, Dodge HT, Francis CK, Hillis D, Ludbrook P et al. Thrombolysis in myocardial infarction (TIMI) trial, Phase I: a comparison between intravenous tissue type plasminogen activator and intravenous atreptokinase. Clinical findings through hospital dis- charge. Circulntion 1987;76:142-154. 8. Baardman T. Hermens WT. Lenderink T, Molhoek GP, Grollier G. Ptisterer M, Simoons ML. Differential effects of tissue plasminogen activator and streptokinase on infarct aise and rate of enzyme release: influence of early infarct related artery patency. The GUSTO Enzyme Substudy. Eur Heart J 1996;17:237-246. 9. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, htreptokinase or both on coronary-artery patency, ventricular function and survival after acute myocardial infarction. N En,ql J Med 1993;329:1615- 1622. IO. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N En,$ J Med 1993;329: 673-682. 1 I. Harmoinen A. Immunoassay of C-reactive protein using the Hitachi 705E analyzer. .l Clin Chem Biochem 1985:23:45-46. 12. van der Laarse A, Hermens WT. Hollaar L. Assessment of myocardial damage in patients with acute myocardial infarction by Eerial measurements of <erum alpha-hydroxybutyrate dehydrogenaae levels. Am Heart J 1984; 107:248- 260. 13. Simer RJ, Top01 EJ, Holmes DR Jr, White HD, Rutsch WR, Vahanian A, Simoons ML, Morris D, Betriu A, Califf RM, Ross AM, for the GUSTO-I Itnutigators. Link between the angiographic substudy and mortality out- comes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery patency. Circulation 1995;91:1923- 1928. 14. Lenderink T, Simoons ML, Van Es GA, Van de Werf F, Verstraete M, Arnold AE, for the European Cooperative Study Group. Benefit of thrombolytic therapy is sustained throughout five years and is related to TIM1 perfusion grade 3 but not grade 2 Row at discharge. Circulntim 1995:92: I I IO-I 116. Clinical and Angiographic Implications of Balloon Rupture During Coronary Stenting Fernando Alfonso, MD, Maria J. Pbrez-Vizcayno, MD, Rosana Hernhdez, MD, Javier Goicolea, MD, Antonio Fernbndez-Ortiz, MD, Camino Bahelos, MD, and Carlos Macaya, MD C oronary stenting is increasingly being used during percutaneous coronary interventions. 1-3 This tech- nique is currently selected not only for patients with suboptimal results or complications after balloon di- lation, but also electively, in an attempt to reduce the restenosis rate.‘,* In the early days, coronary stenting was flawed by a relatively high incidence of subacute From the Interventional Cardiology Unit, San Carlos University Hospi- tal, Madrid, S ain. Dr. Alfonso’s address is: Unidad de Hemodi- nbmrca y Car 8 rologia Intervencionista, Departamento Cardiopulmo- nar, Hospital Universitario “San Curios, ” Ciudad Universitaria, Plaza de Cnsto Rey, Madrid 28040, Spain. Manuscript received April 13, 1997; revised manuscript received and accepted June 19, 1997. 01997 by Excerpta Medica, Inc All riohts reserved. stent thrombosis and the requirement for prolonged anticoagulation, with its associated bleeding compli- cations.’ Today, these 2 important limitations have been mostly overcome by improvements in stent im- plantation techniques. 3 Intravascular ultrasound stud- ies frequently demonstrate inadequate stent deploy- ment (incomplete expansion, suboptimal apposition, or stent asymmetry) even in patients with excellent angiographic results, and that high inflation pressures may help to optimize the implantation of these de- vices.3 This new strategy, namely, using relatively high pressures in conjunction with a simple regimen of antiplatelet therapy, has been associated with ex- 0002.9149/97/s 17.00 1077 PII SOOO2-9149197100607-3 

Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase

Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase

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