In a systematic review published online on May 21st, they note that while beta-blockers are clearly beneficial at some point after STEMI, it is still unclear when the benefit starts to outweigh the potential side effects, such as cardiogenic shock.
“We are disappointed to have found minimal evidence to support any concrete initiation time for beta-blockade in STEMI patients,” first author Dr. Richard Sinert of SUNY-Downstate Medical Center in Brooklyn, New York, and colleagues write in the Annals of Emergency Medicine
“However, beta-blockade should be initiated at some point after the first 24 to 48 hours after symptom onset in myocardial infarction patients, and further study aimed at determining the appropriate timing of beta-blocker initiation will be needed before evidence-based recommendations can be made.”
Dr. Sinert and colleagues searched MEDLINE for randomized trials that compared immediate beta-blockers with placebo for the first 24 to 48 hours and then used the drugs in both groups starting on day 2 or 3. They included patients who were at least 18 years and had recent-onset chest pain (<24 hours) consistent with acute myocardial infarction. They excluded cases without documented STEMI.
Of 340 studies deemed relevant and reviewed, only the TIMI-IIB trial from 1991 appropriately addressed the timing of beta-blockade.
The TIMI-IIB trial was designed to evaluate early versus delayed angiography and percutaneous transluminal coronary in patients who received intravenous recombinant tissue-type plasminogen activator. As a substudy, it also examined the effects of beta-blockade timing. Patients were excluded if they received patients receiving beta-blockers or calcium channel
blockers, had pacemakers, pulse rates less than 55 beats/min at baseline or heart block, systolic blood pressure less than 100 mm Hg, wheezing, or pulmonary edema.
Of 2,934 randomized patients, 1,434 were included in the beta-blocker substudy. They received metoprolol either intravenously within six hours of receiving recombinant tissue-type plasminogen activator (n=720), or orally beginning on day 6 (n=714).
On intention-to-treat analysis, there was no significant difference in the combined relative risk of death or reinfarction, the primary endpoint in Dr. Sinert and colleagues’ analysis. At six days, the relative risk with immediate vs. delayed beta-blockade was 0.67 (95% confidence interval, 0.44-1.03) and at six weeks, it was 0.74 (0.53-1.06).
“Although there were areas of potential bias identified and the study was not powered to address our primary outcome (mortality), the trial was unable to demonstrate benefit or harm for immediate beta-blocker administration,” Dr. Sinert and colleagues write.
Commenting on the trials usually cited by guidelines, they note that, “When 30-day outcomes and any longer-term endpoints are examined, this conflates the question of whether immediate beta-blockade is beneficial, with the known benefits of postinfarction beta-blockade.”
“Unfortunately,” they add “this conflation has led not only to confusion and changes in the AHA guidelines but also to a decades-long conventional wisdom that there was a proven benefit to immediate beta-blockade.”
Ann Emerg Med 2010.