Mid-dose beta-blocker therapy tied to highest mortality reduction after AMI

Use of any beta-blocker dose results in a significant decrease in mortality following acute myocardial infarction (AMI) when compared with no treatment, reports a study. Doses >25 percent to 50 percent of the currently recommended target dose (RTD) are associated with highest mortality reduction within the first year after AMI, indicating that higher doses are not required.

“Our findings support continued use of beta-blocker therapy following AMI to all patients in the absence of contraindications and indicate that maximal mortality reduction may be achieved with mid-dose therapy, potentially reducing healthcare costs and beta-blocker side effects,” the researchers said.

All patients admitted for first-time AMI in Denmark between 1 July 2004 and 31 December 2014 were enrolled in this nationwide cohort study using the Danish National Patient Registry. Those who remained alive 15 days after admission were followed until death, emigration, or 31 December 2014.

The researchers categorized patients according to daily beta-blocker consumption (0 percent, >0 percent to 12.5 percent, >12.5 percent to 25 percent, >25 percent to 50 percent, >50 percent to 100 percent, or 100 percent of the currently RTD) based on prescriptions registered in the Danish National Database of Reimbursed Prescriptions. Doses were updated constantly during follow-up.

Finally, the research team computed the mortality rate ratios (MRRs), with adjustments for confounders, using Cox proportional hazard regression.

A total of 65,125 patients were followed. Any beta-blocker dose given to these patients resulted in a significant mortality reduction relative to no treatment (adjusted MRR, ≤0.92, 95 percent confidence interval [CI], 0.86‒0.98). [Am J Med 2023;136:458-465.E3]

Among the beta-blocker doses, those >25 percent to 50 percent demonstrated the largest decrease in mortality (adjusted MRR, 0.55, 95 percent CI, 0.50‒0.60). After 1 year, the dose category associated with the highest decrease in mortality was >50 percent to 100 percent (adjusted MRR, 0.58, 95 percent CI, 0.50‒0.67), but this did not markedly differ from that with doses >25 percent to 50 percent (adjusted MRR, 0.68, 95 percent CI, 0.61‒0.77).

These findings confirmed previous reports of significant mortality decrease associated with beta-blockers following AMI. [J Am Coll Cardiol 2015;66:1431-1441; J Am Heart Assoc 2016;5(pii):e004190; Am Heart J 2017;184:26-36; Eur Heart J Acute Cardiovasc Care 2021;10:372-379; J Am Heart Assoc 2021;10:e019017; J Cardiovasc Pharmacol 2021;77:87-93]

“In accordance with a study based on the SWEDEHEART registry, our study demonstrated that higher beta-blocker doses are not associated with improved outcomes,” the researchers said. “Furthermore, our study included a refined dose categorization, allowing for identification of significant differences in mortality between individual dose groups.” [Eur Heart J Acute Cardiovasc Care 2021;10:372-379]

Current evidence from observational data show that maximal mortality reduction is achieved with beta-blocker doses below RTDs used in trials establishing their efficacy. Doses >25 percent to 50 percent of RTD, in particular, is associated with nearly 50-percent lower mortality relative to no treatment 1 year following AMI, according to the researchers.

“These findings are reassuring because of consistent reports of low-dose beta-blocker treatment at discharge and infrequent up-titration,” they said. [Am Heart J 2010;160:435-442; J Am Coll Cardiol 2013;62:1791-1801; J Am Coll Cardiol 2015;66:1431-1441; Circ J 2015;79:632-640]

“However, our findings also underscore the need for reinforced efforts to increase the proportion of patients taking any beta-blocker following acute myocardial infarction, as one in four potential new beta-blocker users was alive 1 month after discharge but had not redeemed a prescription and was thus unlikely to receive any beta-blocker treatment,” the researchers noted.