Table 2. Primary and Secondary Study Outcomes in OPERA, According to Treatment Assignment.
| Outcome | Placebo (n=758) |
n-3-PUFA (n=758) |
Odds Ratio or Hazard Ratio* (95% CI) |
P value† | |
|---|---|---|---|---|---|
|
Any first post-op AF, primary endpoint, n (%) ‡ |
233 (30.7) | 227 (30.0) | 0.96 (0.77, 1.20) | 0.74 | |
| Post-op AF, secondary endpoints | |||||
| Sustained, symptomatic, or treated post-op AF, n (%) § |
231 (30.5) | 224 (29.6) | 0.96 (0.77, 1.19) | 0.70 | |
| Post-op AF excluding flutter, n (%)∥ | 220 (29.0) | 217 (28.6) | 0.98 (0.79, 1.23) | 0.87 | |
| No. of post-op AF episodes, n (%) | 1 | 156 (20.6) | 157 (20.7) | ||
| 2 | 59 (7.8) | 49 (6.5) | n/a | 0.73 | |
| 3+ | 18 (2.4) | 21 (2.8) | |||
| Total in-hospital days with any post-op | 2.75 (2.1) | 2.84 (2.1) | n/a | 0.58 | |
| AF, mean (SD) ¥ | |||||
| Proportion of in-hospital days free of any post-op AF, percent |
89.0 | 88.7 | n/a | 0.88 | |
| Other arrhythmias, n (%) | |||||
| Other supraventricular tachycardia | 6 (0.8) | 11 (1.5) | 1.85 (0.68, 5.02) | 0.33 | |
| Ventricular tachycardia or fibrillation | 9 (1.2) | 5 (0.7) | 0.55 (0.18, 1.66) | 0.42 | |
| Other endpoints, n (%) | |||||
| MACE, in-hospital ¶ | 20 (2.6) | 13 (1.7) | 0.62 (0.31, 1.25) | 0.18 | |
| Myocardial infarction | 10 (1.3) | 10 (1.3) | 0.99 (0.41, 2.39) | 1.00 | |
| Stroke | 8 (1.1) | 4 (0.5) | 0.45 (0.13, 1.51) | 0.18 | |
| Cardiovascular death | 3 (0.4) | 0 (0.0) | n/a | 0.08 | |
| Arterial thromboembolism, 30 days | 13 (1.7) | 5 (0.7) | 0.37 (0.13-1.03) | 0.047 | |
| Arterial thromboembolism or death, 30 days |
27 (3.6) | 13 (1.7) | 0.43 (0.22-0.84) | 0.01 | |
| Total mortality, 30 days | 15 (2.0) | 8 (1.1) | 0.53 (0.23-1.26) | 0.14 | |
| - Cardiac arrhythmic | 0 (0.0) | 1 (0.1) | -- | 0.32 | |
| - Cardiac nonarrhythmic | 2 (0.3) | 0 (0.0) | -- | 0.16 | |
| - Vascular | 3 (0.4) | 0 (0.0) | -- | 0.08 | |
| - Noncardiovascular | 10 (1.3) | 7 (0.9) | 0.70 (0.27-1.84) | 0.47 | |
| Resource utilization, median (25th, 75th %) | |||||
| Total ICU/CCU stay, days | 2 (1, 3) | 2 (1, 3) | n/a | 0.38 | |
| Total telemetry monitoring, days | 6 (5, 7) | 6 (5, 7) | n/a | 0.39 | |
| Total hospital stay, days | 7 (5, 8) | 7 (5, 9) | n/a | 0.48 | |
All analyses were based on intention-to-treat. Values are odds ratios estimated using logistic regression for post-op AF and other arrhythmias; and hazard ratios estimated using Cox proportional hazards for other endpoints such as MACE.
Determined using Pearson chi-square (or Fisher exact tests for cells<10) for the primary post-op AF endpoint, the first two secondary post-op AF endpoints, and other tachyarrhythmias; Poisson regression for the total number of post-op AF events per patient and the total number of in-hospital days with one or more episodes of post-op AF; the Wilcoxon rank-sum test for the proportion of in-hospital days free of any post-op AF and days of resource utilization; and the log-rank test for MACE, arterial thromboembolism, and mortality endpoints.
The median (25th, 75th %) duration of the first post-op AF episode was 0.92 (0.17, 1.0) days in the placebo group and 1.0 (0.17, 1.0) days in the n-3-PUFA group (Wilcoxon rank-sum P=0.62).
A total of 661 post-op AF episodes occurred in 460 patients. Among these episodes, 8.9% were associated with dyspnea, chest pain, or hypotension requiring escalation of therapy; 76.7% were treated with electrical or pharmacological cardioversion (predominantly amiodarone); 87.4% lasted more than 1 hour; and 97.9% met one or more of these criteria.
Excluding atrial flutter and supraventricular tachycardia with some but not all characteristics consistent with atrial fibrillation.
Among the 460 patients with post-op AF. Among all 1,516 patients, the corresponding values were 0.8 (1.7) days in the placebo group and 0.8 (1.7) days in the n-3-PUFA group (P=0.93).
See Supplementary Table 2 for detailed definitions of all events. Analyses of individual MACE components include all subtypes of events occurring in any patient.
Post-op AF = post-operative atrial fibrillation or flutter. MACE = myocardial infarction, stroke, or cardiovascular death. ICU/CCU = intensive care unit/coronary care unit.