Intravenous Beta Blockers for Acute Myocardial Infarction
Abstract & Commentary
Synopsis: Atenolol improves outcomes in acute MI treated with thrombolytics, but early IV atenolol is of little value. They recommend starting oral atenolol as soon as the patient is stable.
Source: Pfisterer M, et al. J Amer Coll Cardiol 1998; 32:634-640.
In the prethrombolytic era, the early administration of intravenous (IV) beta blockers in acute myocardial infarction (MI) was shown to improve survival. However, physicians were concerned about acute negative inotropic effects and were confused by studies showing mortality reductions even if beta blockers were started one month after MI. In the thrombolytic era, the benefits of early IV beta blockers were less conclusively shown. Thus, a prospectively planned observational analysis of the Global Utilization of Streptokinase and Thrombolysis for Occluded Coronary Arteries (GUSTO-1) data on beta blocker use is of interest. The protocol recommended atenolol be given as soon as possible after enrollment in patients without hypotension, bradycardia, or heart failure, followed by oral therapy. Five subgroups were analyzed: no atenolol; IV only; oral only; IV plus oral; Of the 41,000 patients enrolled, 75% received any atenolol. In general, those receiving atenolol were younger, had higher blood pressure, lower heart failure class, and more likely had anterior MI. Thirty-day mortality adjusted for baseline differences was lower in the atenolol-treated patients, but mortality was higher in those who received IV and oral atenolol vs. those who received only oral (RR, 1.2; P < 0.001). Also, intravenous atenolol use was associated with higher incidences of heart failure, shock, recurrent ischemia, and pacemaker use compared to oral atenolol. Intracranial hemorrhage rates were not lower with IV atenolol even in those patients who presented with systolic blood pressure more than 160 mmHg. In addition, reinfarction rates were unaffected by IV atenolol vs. oral atenolol and were higher in those given any atenolol. Pfisterer and colleagues conclude that atenolol improves outcomes in acute MI treated with thrombolytics, but early IV atenolol is of little value. They recommend starting oral atenolol as soon as the patient is stable.
Comment by Michael H. Crawford, MD
This analysis of the GUSTO-1 study confirms the concerns of practicing physicians who struggled with the obvious complications of IV beta blockers for acute MI and the "evidence based medicine Gestapo’s" admonition that IV beta blockers saved more lives. The concerns of real doctors caring for real patients seems to have won—IV beta blockers provide little or no additional benefit. There was a reduction in cardiac rupture-related tamponade with IV atenolol (0.6% vs 0.9%; P < 0.001), but this effect is inconsequentially small. On the other hand, heart failure, cardiogenic shock, heart block, recurrent infarction, and ischemia were all increased by IV atenolol. These results occurred despite the selection bias toward giving IV atenolol to the less sick individuals that one would expect in an observational study.
The data are particularly robust because 75% of the more than 41,000 patients received atenolol, 44% IV as compared to U.S. MI registry data showing 36% beta blocker use and 17% IV. Obviously, physicians in the United States have been voting with their feet on this issue, but the perceived problems with IV beta blockade early post MI may be contributing to the general low usage of beta blockers in general in the United States. Had the trialists not pushed IV therapy so hard, overall beta blocker use may have been higher in the United States.
Interestingly, the ACC/AHA guidelines for the treatment of acute MI suggest IV beta blockers especially for those with hypertension or tachycardia, yet neither subgroup did better with IV atenolol in this analysis. Also, ischemia and reinfarction were actually increased with IV atenolol use. These results fly against the common conception that beta blockers work by decreasing myocardial oxygen demand. Perhaps they have other beneficial effects not predicted by determinants of oxygen demand or perhaps lowering blood pressure is detrimental to coronary blood flow in acute MI and is ill advised. Epidemiologic studies have consistently shown that the higher your blood pressure, the better your survival with acute MI.
Although this analysis raises many questions that need to be evaluated in a randomized trial, two points seem clear: beta blockers are beneficial to acute MI patients in the thrombolytic era, but they should be given orally only when the patient is hemodynamically stable.