In order to evaluate whether preoperative BB use affects the outcome of prophylactic BB treatment after heart surgery, an analysis was performed using the data of the largest double blind, placebo controlled, randomised trial of prophylactic BB treatment (metoprolol) for reduction in hospital length of stay following heart surgery, known as the β blocker length of stay (BLOS) study.²

In the BLOS study 1000 patients undergoing elective open heart surgery were randomised equally to metoprolol (100–150 mg/day) or double blind placebo, started within 12 hours of arrival in the intensive care unit (ICU) after surgery. The patients were followed for postoperative AF, length of hospital stay, and cost of in-hospital care. A third party payer prospective (Ministry of Health of Canada) was chosen for the cost analysis; costs are quoted in Canadian dollars.

The central question this study addresses is: “Does the therapeutic effect of prophylactic metoprolol use differ according to preoperative BB usage?” Multiple linear regression was used for quantitative outcomes such as length of stay, and multiple logistic regression was used for discrete outcomes such as AF. Tests of interaction were done to assess whether the effect of treatment differed significantly between two different groups of patients. Fisher’s exact test and Student’s t test (both two sided) were used to compare baseline characteristics between the two preoperative BB usage groups.

In the whole study population, prophylactic metoprolol reduced the percentage of patients in whom AF occurred from 39% to 31% (relative risk reduction of 20%, p < 0.01). In the BB group, metoprolol decreased the occurrence of postoperative AF from 40.1% to 29.6%; however, in the no BB group, the risk of AF increased from 35% to 38.5% (p = 0.065, after adjustment for age and type of surgery, p = 0.3).

Overall, metoprolol did not significantly affect either the length of stay in the ICU or length of stay in hospital. However, the effect of prophylactic metoprolol on length of stay differed significantly between patients in the BB and the no BB groups (table 2​2).). For patients in the BB group, length of stay in the ICU and total length of stay were essentially unaffected by metoprolol. For patients in the no BB group, prophylactic metoprolol increased mean (SD) length of stay in the ICU from 31.7 (18.1) to 53.0 (107.8) hours (p = 0.03). There was an increase for total length of stay from 148.0 (59.0) to 183.4 (171.2) hours (p = 0.002). These differences in metoprolol effect between groups remained significant after adjustment for differences in baseline characteristics. The significant interaction between prophylactic metoprolol and preoperative use of BB suggests that prophylactic metoprolol affects these patient populations differently.

This observation is biologically plausible as BB withdrawal is known to create a hyperadrenergic state. If preoperative BB use is important for the benefits of prophylactic BB treatment to occur, then in patients without BB withdrawal (without history of preoperative BB treatment), the potential to achieve a benefit is lessened. However, the potential for BB related side effects remains.

Essentially, patients having CABG in our study were more likely to have received a BB preoperatively than those having valve surgery. It is unlikely that the different ratio of valve to CABG surgery between groups explains the observation of this paper. It is possible that unrecognised contraindications for BB were missed at the time of enrolment into the study, but this is unlikely given the same proportions of patients ventilated for more than three days, reintubated, or requiring a permanent pacemaker.