Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI)

We estimated that a sample size of 300 patients would achieve 80% power to detect a difference of 0.17 between the group proportions of 0.33 and 0.50 at a significance level (ɑ) of 0.05 by using a two-sided z-test with continuity correction, assuming 15% loss to follow-up. This estimate allowed for 1 interim analysis using the O’Brien-Fleming spending function truncated at three standard deviations to determine the test boundaries. The monitoring boundary P values associated with the interim analysis were .003, and the threshold P value for the final analysis was .049.

RESULTS

Study Flow

A total of 453 patients were screened for eligibility. Among these patients, 162 were excluded, and the remaining 291 patients were randomized (Figure 1). Surgery was cancelled in six patients allocated to omission and in four patients allocated to continuation arms, respectively. Moreover, three patients in the omission arm were excluded from the analysis following randomization. Specifically, one was excluded because of early discharge without overnight stay, one was excluded because of withdrawal of consent, and one was excluded because of missing primary outcome data. In addition, three cases in the continuation arm were excluded following randomization because of the preoperative (permanent) discontinuation of ACEI therapy in two cases and discharge without an overnight stay in one case. Finally, 275 patients were included in the analysis: 137 in the ACEI omission group and 138 in the ACEI continuation group. Adherence to allocation was 88% and 92% in the omission and continuation groups, respectively.

Baseline Characteristics

The demographic data of patients allocated to ACEI omission and those allocated to ACEI continuation were similar (Table 1). A large majority of patients in both groups took the ACEI lisinopril. Overall, 187 of 275 (68%) patients were taking at least 1 antihypertensive agent, most commonly a diuretic, in addition to an ACEI. SBP measured during the preoperative clinic visit averaged 136.5 mm Hg and did not differ significantly between groups (P = .84).

Surgical Variables

General anesthesia was the most commonly utilized technique, although spinal and regional anesthesia were also represented (Table 1). The majority of cases in both groups were planning for orthopedic and spinal surgery. The method of anesthesia or type of surgery between patients allocated to ACEI omission and those allocated to continuation did not differ (P = .61 and P = .45 respectively).

Episodes of Intraoperative Hypotension

Intraoperative SBPs are displayed in Figure 2, and hemodynamic outcomes are summarized in Table 2. Episodes of SBP < 80 mm Hg during anesthesia induction were numerically less frequent in the omission group than in the continuation group; the difference between groups, however, was not statistically significant (24 of 137 [18%] vs 38 of 138 [28%], RR: 0.64, 95% CI: 0.40 to 1.00, P = .06).

The primary outcome, episodes of intraoperative SBP < 80 mm Hg, occurred less often in patients allocated to the ACEI omission group than in those allocated to the ACEI continuation group (76 of 137 [55%] vs 95 of 138 [69%], RR: 0.81, 95% CI: 0.67 to 0.97, P = .03). A per-protocol sensitivity analysis of the primary outcome did not substantially alter results (RR: 0.75, 95% CI: 0.61 to 0.91, P = .003). Among the patients, 1 was excluded from the sensitivity analysis because of missing data on adherence to allocation. Of the 171 episodes of intraoperative SBP < 80 mm Hg, 149 were associated with vasopressor administration (61 of 76 [80%] omission vs 88 of 95 continuation [93%], RR: 0.87, 95% CI: 0.76 to 0.98, P = .02). Episodes of intraoperative SBP < 80 associated with vasopressor administration occurred less frequently in patients allocated to the omission group than in those allocated to the continuation group (61/137 [45%] vs 88/138 [64%], RR: 0.70, 95% CI: 0.56-0.87, P < .01). Few patients in either group developed severe intraoperative hypotension, which was defined as SBP < 60 mm Hg (6 of 137 [4%] omission vs 7 of 138 [5%] continuation, RR: 0.86, 95% CI: 0.30 to 25.0, P = 1.0). The number of patients needing to continue ACEI therapy preoperatively to cause 1 additional episode of harm in the form of intraoperative SBP < 80 mm Hg was 7.5 (NNH 7.5).