Comparison of carvedilol and metoprolol in patients with acute myocardial infarction undergoing primary coronary intervention--the PASSAT Study.
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.).


CONCLUSIONS
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.
Tölg
R
R
Herzzentrum Segeberger Klinken GmbH, Am Kurpark 1, 23795 Bad Segeberg, Germany. ralph.toelg@segebergerkliniken.de
Witt
M
M
Schwarz
B
B
Kurz
T
T
Kurowski
V
V
Hartmann
F
F
Geist
V
V
Richardt
G
G
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D015906:Angioplasty, Balloon, Coronary / Q000706:statistics & numerical data*; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D015897:Comorbidity; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged; D009203:Myocardial Infarction; D011379:Prognosis; D011412:Propanolamines / Q000008:administration & dosage*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology* / Q000517:prevention & control*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol