In-hospital double-dose influenza vaccine reduces MACE and death in ACS patients with prior stroke compared to delayed standard-dose

This study was a subanalysis of the VIP-ACS trial, a randomized, pragmatic, multicenter, open-label trial with blinded-adjudication endpoints. The setting was in-hospital, involving adult patients with acute coronary syndrome (ACS) who were hospitalized for seven days or less. The population included 1801 patients, of whom 67 had a history of stroke. The intervention was an in-hospital double-dose quadrivalent inactivated influenza vaccine. The comparator was a standard-dose vaccine administered at 30 days post-randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analyzed using the win ratio method. The follow-up period covered 12 months of each influenza season.

The primary hierarchical endpoint results showed no significant differences between groups for patients without a history of stroke. In this subgroup, the win ratio (WR) was 0.94. Absolute numbers indicated 11.4% wins (862 patients) in the double-dose group versus 12.1% wins (872 patients) in the standard-dose group. The 95% confidence interval was 0.72-1.24, with a p-value of 0.69, indicating no difference in outcomes.

In contrast, for patients with a history of stroke, the in-hospital double-dose vaccination favored this group. The win ratio was 2.62. Absolute numbers showed 43.9% wins versus 16.8% wins in the standard-dose group. The 95% confidence interval was 1.10-6.25, with a p-value of 0.03, indicating a statistically significant benefit for the double-dose intervention in this specific subgroup.

Key secondary outcomes included a hierarchical composite consisting of cardiovascular death, myocardial infarction, and stroke (MACE). For patients with a history of stroke, the in-hospital double-dose vaccination again favored this group. The win ratio was 3.01. Absolute numbers were 41.3% wins versus 13.7% wins. The 95% confidence interval was 1.15-7.88, with a p-value of 0.02, further supporting the benefit of early double-dose vaccination in those with prior stroke history.

Safety and tolerability findings were not reported in the provided data. Adverse events, serious adverse events, discontinuations, and tolerability metrics were not reported. Consequently, a detailed assessment of the safety profile of the in-hospital double-dose regimen versus the delayed standard-dose regimen cannot be made from this specific dataset.

These results compare to prior landmark studies by highlighting the potential importance of vaccination timing and dosing in high-risk populations. While prior studies often focus on general influenza vaccination efficacy, this subanalysis suggests that in-hospital administration of a double dose may be particularly beneficial for patients with ACS and a history of stroke. However, the lack of reported safety data limits direct comparison with standard vaccination protocols regarding adverse event profiles.

Key methodological limitations include the fact that this is a subanalysis of a larger trial. The subgroup of patients with a history of stroke was small (67 patients), which may affect the precision of the estimates, although the confidence intervals did not cross the null value for the primary and secondary outcomes in this subgroup. The study was open-label, which could introduce bias in outcome assessment, though endpoints were adjudicated blindly. Additionally, the lack of reported safety data is a significant limitation for clinical decision-making.

Clinical implications suggest that for patients with acute coronary syndrome and a history of stroke, in-hospital double-dose influenza vaccination may prevent hospitalizations and death compared with standard-dose vaccination at 12 months. This finding could influence practice decisions regarding vaccination timing and dosing in high-risk cardiovascular patients. However, clinicians must weigh these potential benefits against the lack of reported safety data and the specific context of the subgroup analysis.

Several questions remain unanswered. The lack of safety data raises concerns about the tolerability of the in-hospital double-dose regimen. It is unclear if the observed benefits in the stroke subgroup are applicable to other high-risk groups without prior stroke. Furthermore, the long-term durability of the immune response from an in-hospital double dose compared to standard protocols remains unknown. Future research should aim to address these safety and efficacy gaps.