Abstract 16045: Is Low Dose Beta Blocker Equivalent to High Dose for Reducing Major Adverse Cardiovascular Events?

Abstract

Introduction: Beta-blockers (BB) are a fundamental component of care for patients (pts) with coronary artery disease (CAD) and acute coronary syndromes (ACS). BB therapy based on decades-old trials generally targets high doses (HD). Yet, whether better-tolerated low-dose (LD) BB is as effective in the current era of medical and interventional therapy has not been tested. Hypothesis: LD BB is equivalent to HD BB for major adverse cardiovascular events (MACE), i.e., all-cause death, myocardial infarction, and stroke, in patients (pts) with symptomatic CAD. Methods: Intermountain Healthcare pts with CAD documented at coronary angiography (n=12,882; 60.9% with ACS) were studied. BB use and dose were determined at discharge and 6 mo. LD was defined as ≤25% and HD as ≥50% of the equivalent of 200 mg metoprolol. Univariate testing of associations between BB usage and clinical characteristics was performed using chi-square and Wilcoxon tests. Significant factors were entered into logistic regressions to calculate propensity scores. Equivalence testing was done using time until MACE for 0 to 6 mo, 7 to 24 mo, and combined periods using the Wellek method based on Cox proportional hazards and an assumed risk function within 0.15. Results: 7158 (55.6%) of pts were discharged on BB: 6078 (85.0%) on LD and 974 (13.6%) on HD. Within 6 mo, 263 (4.3%) of LD compared to 47 (4.8%) of HD pts had a MACE. After adjusting for propensity score, MACE on LD versus HD BB was equivalent (p=0.036) but not superior (HR= 0.92; 95% CI: 0.67, 1.28). For 7 to 24 mo, of the 7090 pts without a prior MACE, 5868 (82.8%) were on LD and 1145 (16.1%) on HD BB, and 433 (7.4%) of LD versus 109 (9.5%) of HD pts had a MACE. After adjusting for propensity score, LD again was equivalent to HD (p<0.005) but not superior (HR=0.98; CI: 0.76, 1.26). Outcome for pts on LD versus HD over the entire 0-24 mo period was equivalent (p=0.002) and nearly superior (HR=0.86; CI: 0.71-1.05). ACS pts also showed dose equivalence (p=0.02) and near LD superiority (HR=0.82; CI: 0.64-1.04). Conclusions: In the modern era of advanced medical and interventional therapy for symptomatic CAD and ACS, LD BB is associated with at least equivalent cardiovascular protection as HD and should be encouraged when HD BB is not tolerated or contraindicated.