BackgroundAlthough current guidelines endorse early beta-blocker therapy in stable patients with STEMI, there is no clear recommendation on the early use of these drugs in patients with NSTEMI. MethodsLiterature search was conducted by 3 independent researchers using PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS. Studies were eligible if (P) patients included were ≥ 18 years of age and had non-ST-segment elevation myocardial infarction (NSTEMI), (I) early (<24 h) treatment with intravenous or oral beta-blockers was compared to (C) no treatment with beta-blockers and data on (O) in-hospital mortality and/or in-hospital cardiogenic shock were depicted. Odds ratios and 95% confidence intervals were calculated using random effects models with the Mantel–Haenszel method. The Hartung-Knapp-Sidik-Jonkman method was used as estimator for τ2. Results977 records were screened for eligibility, which led to the inclusion of 4 retrospective, nonrandomized, observational cohort studies comprising a total of N = 184,951 patients. After pooling of the effect sizes, early therapy with beta-blockers resulted in a reduction of in-hospital mortality (OR 0.43 [0.36–0.51], p = 0.0022) despite no significant effect on the prevalence of cardiogenic shock (OR 0.36 [0.07–1.91], p = 0.1196). ConclusionEarly treatment with beta-blockers was associated with an attenuation of in-hospital mortality despite no increase in cardiogenic shock. Thus, early therapy with these drugs could elicit beneficial effects on top of reperfusion therapy, similar to the effects seen in STEMI-patients. The low number of studies (k = 4) has to be considered when interpreting the findings of this analysis.