Table 2. Primary End Point Analysis of Survival Free of Nonsurgical Major Hemocompatibility-Related Adverse Events.
| Primary analysis population outcomes | No./total No. (%) | Difference (lower 97.5% confidence limit), % | P value | |
|---|---|---|---|---|
| Placebo (n = 296) | Aspirin (n = 293) | |||
| Noninferiority primary end point analysis (success)a | 201/271 (74.2) | 186/273 (68.1) | 6.0 (−1.6) | <.001 |
| Withdrawn patients without primary end point eventb | 25/296 (8.4) | 20/293 (6.8) | ||
| First event that resulted in treatment failurec | ||||
| Death | 4/271 (1.5) | 4/273 (1.5) | ||
| Bleeding | 61/271 (22.5) | 77/273 (28.2) | ||
| Stroke | 5/271 (1.8) | 6/273 (2.2) | ||
| Arterial peripheral thromboembolism | 0/271 | 0/273 | ||
| Pump thrombosis | 0/271 | 0/273 | ||
The primary end point is a composite of survival free of nonsurgical (>14 days after implant) major hemocompatibility-related adverse events (bleeding, stroke, pump thrombosis, or arterial peripheral thromboembolism) at 12 months after implant. Transplant, explant due to recovery, or transition to open-label aspirin use prior to 12 months without prior nonsurgical major hemocompatibility-related adverse events is considered a success. The rates of success in this category were 9.2% (25/271) in the placebo group vs 10.3% (28/273) in the aspirin group. Details of major surgical adverse events occurring less than or equal to 14 days after implant are provided in eTable 5 in Supplement 2.
The noninferiority end point was calculated excluding patients who were withdrawn without a primary end point event. Worst-case scenario allocation of withdrawn patients without primary end point event, specifically all patients in the placebo group considered as a treatment failure and all in the aspirin group considered a success, continued to demonstrate noninferiority (P = .02) as shown in eTable 6 in Supplement 2. Additional sensitivity analyses, specifically the evaluation of the primary end point as intent to treat and analysis of the primary analysis population as time to first event including follow-up after transition to open-label aspirin use, are also shown in eTable 6 and eFigures 3 and 4 in Supplement 2. Results of all sensitivity analyses agree with the primary end point analysis.
The event that occurred first was noted as the event resulting in treatment failure in the component analysis. Subsequent events were not accounted for in this analysis. Time-to-event analyses are shown in Figure 2 and eFigure 5 in Supplement 2. Death rates in the primary analysis population in the study were 7.1% (21/296) in the placebo group vs 7.5% (22/273) in the aspirin group (causes of death are shown in eTable 7 in Supplement 2). Death due to any cause (eFigure 7), competing outcomes (eFigure 8), and rate of bleeding events (eFigure 9) among the randomized population are shown in Supplement 2. Overall event rates, including recurrent events for bleeding, stroke, arterial peripheral thromboembolism, and pump thrombosis are depicted in Figure 3.