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Comparison of carvedilol and metoprolol in patients with acute myocardial infarction undergoing primary coronary intervention

—The PASSAT Study

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Summary

Background

The value of early therapy with beta-blocking agents in acute myocardial infarction (AMI) undergoing reperfusion is not yet well established. Newer beta-blocking agents such as carvedilol offer potential advantages in the setting of ischemia and reperfusion injury.

Methods

We randomized 100 patients with acute ST-elevation myocardial infarction (STEMI) to receive either 12.5 mg carvedilol or 50 mg metoprolol tartrate orally already before percutaneous coronary intervention (PCI) of the infarct-related artery, uptitrating to a daily target dose of 50 mg carvedilol or 150 mg metoprolol during the first week. Pts. were subjected to left ventricular (LV) angiography just before reperfusion and after 14 days to compare ejection fraction (EF) and regional wall motion abnormalities by quantitative LV analysis. Furthermore, kinetics of cardiac troponin T (cTnT), NT-proANP, NT-proBNP, endothelin, argenine vasopressin, epinephrine and norepinephrine were assessed during the first 12 hours and again at 2 weeks. In addition, reperfusion-induced rhythm abnormalities like VT, triplets, couplets, and bradycardic events were assessed continuously during the first 12 hours starting at reperfusion by Holter analysis.

Results

Both groups did not differ with respect to onset of pain, target vessel, extent of coronary heart disease, age, gender, rate of stenting or use of a GP IIb/IIIa inhibitor, pre- and postinterventional TIMI flow grade, time course of heart rate or blood pressure. There were neither significant differences in the cardiac and neurohumoral markers nor in the occurrence of arrhythmias between both treatment groups. Within 14 days, EF improved by 5.8±2.0% (mean±SEM) in the metoprolol group and by 5.2±2.1% in the carvedilol group (n.s.). Area of infarction was reduced by 6.1±2.9% in the metoprolol group and by 12.8±3.6% of total LV outline in the carvedilol group (n.s.). Maximum hypokinesia in the central infarcted region was diminished by 0.40±0.11 standard deviation (SD) in the metoprolol group and by 0.34±0.13 SD in the carvedilol group (n.s.).

Conclusion

In the setting of direct PCI in acute STEMI, administration of carvedilol before reperfusion appears not to be superior to metoprolol with respect to myocardial injury and improvement of global and regional LV function. The study documents equivalent improvement of LV function and similar kinetics of cardiac and neurohumoral markers in pts. with acute STEMI undergoing direct PCI if the pts. were immediately treated with either carvedilol or metoprolol. Thus, superiority of carvedilol in experimental studies did not translate into a clinical benefit.

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References

  1. The MIAMI Trial Research Group (1985) Metoprolol in acute myocardial infarction (MIAMI). A randomised placebo-controlled international trial. Eur Heart J 6:199–226

    Google Scholar 

  2. ISIS-I-Arbeitsgruppe (1986) ISIS-I Collaborative Group (First International Study of Infarct Survival): Randomised trial of intravenous atenolol among 16027 cases of suspected acute myocardial infarction. Lancet 2:57–66

    Google Scholar 

  3. Roberts R, Rogers WJ, Müller HS et al (1991) Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study. Circulation 83:422–437

    CAS  PubMed  Google Scholar 

  4. Basu S, Senior R, Raval U et al (1997) Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial. Circulation 96:183–191

    CAS  PubMed  Google Scholar 

  5. Tölg R, Kurz T, Ungerer M et al (1997) Influence of alpha- and betaadrenoceptor antagonists on ventricular fibrillation in ischemic rat heart. Naunyn-Schmiedeberg’s Arch Pharmacol 356:62–68

    Google Scholar 

  6. Schäfer U, Kurz T, Jain D et al (2002) Impaired coronary flow and left ventricular dysfunction after mechanical recanalization in acute myocardial infarction: role of neurohumoral activation? Basic Res Cardiol 97:399–408

    PubMed  Google Scholar 

  7. Gregorini L, Marco J, Kozakova M et al (1999) Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction. Circulation 99:482–490

    CAS  PubMed  Google Scholar 

  8. Communal C, Singh K, Sawyer DB et al (1999) Opposing effects of β1- and β2-adrenergic receptros on cardiac myocyte apoptosis. Circulation 100:2210–2212

    CAS  PubMed  Google Scholar 

  9. Bril A, Slivjak M, DiMartino M et al (1992) Cardioprotective effects of carvedilol, a novel beta adrenoceptor antagonist with vasodilating properties, in anaesthetised minipigs: comparison with propranolol. Cardiovas Res 26:518–525

    CAS  Google Scholar 

  10. Feuerstein G, Liu GL, Yue TL et al (1998) Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model. Eur J Pharmacol 351:341–350

    Article  CAS  PubMed  Google Scholar 

  11. Khandoudi N, Percevault-Albadine J, Bril A (1998) Comparative effects of carvedilol and metoprolol on cardiac ischemia reperfusion injury. J Cardiovasc Pharmacol 32:443–451

    Article  CAS  PubMed  Google Scholar 

  12. Gao F, Chen J, Lopez BL et al (2000) Comparision of bisoprolol and carvedilol cardioprotection in a rabbit ischemia and reperfusion model. Eur J Pharmacol 406:109–116

    CAS  PubMed  Google Scholar 

  13. Poole-Wilson PA, Swedberg K, Cleland JGF et al (2003) Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 362:7–13

    CAS  PubMed  Google Scholar 

  14. Sheehan FH, Bolson EL, Dodge HT et al (1986) Advantages and applications of the centerline method for characterising regional ventricular function. Circulation 74:293–305

    CAS  PubMed  Google Scholar 

  15. Sheehan FH, Doerr R, Schmidt WG et al (1988) Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinent of survival. J Am Coll Cardiol 12:289–300

    CAS  PubMed  Google Scholar 

  16. Sandberg A, Blomqvist I, Jonsson UE et al (1988) Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets. Eur J Clin Pharmacol 33(Suppl):9–14

    Google Scholar 

  17. Neugebauer G, Akpan W, Kaufmann B et al (1990) Stereoselective disposition of carvedilol in man after intravenous and oral administration of the racemic compound. Eur J Clin Pharmacol 38(Suppl 2):108–111

    Article  Google Scholar 

  18. Neumann FJ, Blasini R, Schmitt C et al (1998) Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 98:2695–2701

    CAS  PubMed  Google Scholar 

  19. Rupprecht HJ, vom Dahl J, Terres Wet al (2000) Cardioprotective effects of the Na+/H+ exchange inhibitor cariporide in patients with acute anterior myocardial infarction undergoing direct PTCA. Circulation 101:2902–2908

    CAS  PubMed  Google Scholar 

  20. Marzilli M, Orsini E, Marraccini P et al (2000) Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation 101:2154–2159

    CAS  PubMed  Google Scholar 

  21. Britten MB, Abolmaali ND, Assmus B et al (2003) Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 108:2212–2218

    Article  CAS  PubMed  Google Scholar 

  22. Giannitsis E, Müller-Bardorff M, Lehrke S et al (2001) Admission troponin T level predicts clinical outcomes, TIMI flow, and myocardial tissue perfusion after primary percutaneous intervention for acute ST-segment elevation myocardial infarction. Circulation 104:630–635

    CAS  PubMed  Google Scholar 

  23. Tanasijevic MJ, Cannon CP, Antman EM et al (1999) Myoglobin, creatinekinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B. J Am Coll Cardiol 34:739–747

    Article  CAS  PubMed  Google Scholar 

  24. Bolli R (1992) Myocardial stunning in man. Circulation 86:1671–1691

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Herzzentrum Segeberger Klinken GmbH, Am Kurpark 1, 23795, Bad Segeberg, Germany

    R. Tölg, B. Schwarz, V. Geist & G. Richardt

  2. I. Medizinische Klinik, Diakoniekrankenhaus, Elise-Averdieck-Straße 17, 27356, Rotenburg (Wümme), Germany

    M. Witt

  3. Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Alle 160, 23538, Lübeck, Germany

    T. Kurz, V. Kurowski & F. Hartmann

Authors
  1. R. Tölg
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  2. M. Witt
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  3. B. Schwarz
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  4. T. Kurz
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  5. V. Kurowski
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  6. F. Hartmann
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  7. V. Geist
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  8. G. Richardt
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Correspondence to R. Tölg.

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Tölg, R., Witt, M., Schwarz, B. et al. Comparison of carvedilol and metoprolol in patients with acute myocardial infarction undergoing primary coronary intervention. Clin Res Cardiol 95, 31–41 (2006). https://doi.org/10.1007/s00392-006-0317-7

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  • DOI: https://doi.org/10.1007/s00392-006-0317-7

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