tetano
Editor, Senior Moderator
JAMA
. 2020 Dec 4.
doi: 10.1001/jama.2020.23649. Online ahead of print.
Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial
Orly Vardeny[SUP] 1 [/SUP], KyungMann Kim[SUP] 2 [/SUP], Jacob A Udell[SUP] 3 [/SUP], Jacob Joseph[SUP] 4 5 [/SUP], Akshay S Desai[SUP] 5 [/SUP], Michael E Farkouh[SUP] 6 [/SUP], Sheila M Hegde[SUP] 5 [/SUP], Adrian F Hernandez[SUP] 7 [/SUP], Allison McGeer[SUP] 8 [/SUP], H Keipp Talbot[SUP] 9 [/SUP], Inder Anand[SUP] 1 [/SUP], Deepak L Bhatt[SUP] 5 [/SUP], Christopher P Cannon[SUP] 5 [/SUP], David DeMets[SUP] 2 [/SUP], J Michael Gaziano[SUP] 4 5 [/SUP], Shaun G Goodman[SUP] 10 [/SUP], Kristin Nichol[SUP] 1 [/SUP], Matthew C Tattersall[SUP] 11 [/SUP], Jonathan L Temte[SUP] 12 [/SUP], Janet Wittes[SUP] 13 [/SUP], Clyde Yancy[SUP] 14 [/SUP], Brian Claggett[SUP] 15 [/SUP], Yi Chen[SUP] 2 [/SUP], Lu Mao[SUP] 2 [/SUP], Thomas C Havighurst[SUP] 2 [/SUP], Lawton S Cooper[SUP] 16 [/SUP], Scott D Solomon[SUP] 5 [/SUP], INVESTED Committees and Investigators
Affiliations
Abstract
Importance: Influenza is temporally associated with cardiopulmonary morbidity and mortality among those with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher influenza vaccine dose has been associated with reduced risk of influenza illness.
Objective: To evaluate whether high-dose trivalent influenza vaccine compared with standard-dose quadrivalent influenza vaccine would reduce all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.
Design, setting, and participants: Pragmatic multicenter, double-blind, active comparator randomized clinical trial conducted in 5260 participants vaccinated for up to 3 influenza seasons in 157 sites in the US and Canada between September 21, 2016, and January 31, 2019. Patients with a recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor were eligible.
Interventions: Participants were randomly assigned to receive high-dose trivalent (n = 2630) or standard-dose quadrivalent (n = 2630) inactivated influenza vaccine and could be revaccinated for up to 3 seasons.
Main outcomes and measures: The primary outcome was the time to the composite of all-cause death or cardiopulmonary hospitalization during each enrolling season. The final date of follow-up was July 31, 2019. Vaccine-related adverse events were also assessed.
Results: Among 5260 randomized participants (mean [SD] age, 65.5 [12.6] years; 3787 [72%] men; 3289 [63%] with heart failure) over 3 influenza seasons, there were 7154 total vaccinations administered and 5226 (99.4%) participants completed the trial. In the high-dose trivalent vaccine group, there were 975 primary outcome events (883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause) among 884 participants during 3577 participant-seasons (event rate, 45 per 100 patient-years), whereas in the standard-dose quadrivalent vaccine group, there were 924 primary outcome events (846 hospitalizations for cardiovascular or pulmonary causes and 78 deaths from any cause) among 837 participants during 3577 participant-seasons (event rate, 42 per 100 patient-years) (hazard ratio, 1.06 [95% CI, 0.97-1.17]; P = .21). In the high-dose vs standard-dose groups, vaccine-related adverse reactions occurred in 1449 (40.5%) vs 1229 (34.4%) participants and severe adverse reactions occurred in 55 (2.1%) vs 44 (1.7%) participants.
Conclusions and relevance: In patients with high-risk cardiovascular disease, high-dose trivalent inactivated influenza vaccine, compared with standard-dose quadrivalent inactivated influenza vaccine, did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations. Influenza vaccination remains strongly recommended in this population.
Trial registration: ClinicalTrials.gov Identifier: NCT02787044.
. 2020 Dec 4.
doi: 10.1001/jama.2020.23649. Online ahead of print.
Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial
Orly Vardeny[SUP] 1 [/SUP], KyungMann Kim[SUP] 2 [/SUP], Jacob A Udell[SUP] 3 [/SUP], Jacob Joseph[SUP] 4 5 [/SUP], Akshay S Desai[SUP] 5 [/SUP], Michael E Farkouh[SUP] 6 [/SUP], Sheila M Hegde[SUP] 5 [/SUP], Adrian F Hernandez[SUP] 7 [/SUP], Allison McGeer[SUP] 8 [/SUP], H Keipp Talbot[SUP] 9 [/SUP], Inder Anand[SUP] 1 [/SUP], Deepak L Bhatt[SUP] 5 [/SUP], Christopher P Cannon[SUP] 5 [/SUP], David DeMets[SUP] 2 [/SUP], J Michael Gaziano[SUP] 4 5 [/SUP], Shaun G Goodman[SUP] 10 [/SUP], Kristin Nichol[SUP] 1 [/SUP], Matthew C Tattersall[SUP] 11 [/SUP], Jonathan L Temte[SUP] 12 [/SUP], Janet Wittes[SUP] 13 [/SUP], Clyde Yancy[SUP] 14 [/SUP], Brian Claggett[SUP] 15 [/SUP], Yi Chen[SUP] 2 [/SUP], Lu Mao[SUP] 2 [/SUP], Thomas C Havighurst[SUP] 2 [/SUP], Lawton S Cooper[SUP] 16 [/SUP], Scott D Solomon[SUP] 5 [/SUP], INVESTED Committees and Investigators
Affiliations
- PMID: 33275134
- DOI: 10.1001/jama.2020.23649
Abstract
Importance: Influenza is temporally associated with cardiopulmonary morbidity and mortality among those with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher influenza vaccine dose has been associated with reduced risk of influenza illness.
Objective: To evaluate whether high-dose trivalent influenza vaccine compared with standard-dose quadrivalent influenza vaccine would reduce all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.
Design, setting, and participants: Pragmatic multicenter, double-blind, active comparator randomized clinical trial conducted in 5260 participants vaccinated for up to 3 influenza seasons in 157 sites in the US and Canada between September 21, 2016, and January 31, 2019. Patients with a recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor were eligible.
Interventions: Participants were randomly assigned to receive high-dose trivalent (n = 2630) or standard-dose quadrivalent (n = 2630) inactivated influenza vaccine and could be revaccinated for up to 3 seasons.
Main outcomes and measures: The primary outcome was the time to the composite of all-cause death or cardiopulmonary hospitalization during each enrolling season. The final date of follow-up was July 31, 2019. Vaccine-related adverse events were also assessed.
Results: Among 5260 randomized participants (mean [SD] age, 65.5 [12.6] years; 3787 [72%] men; 3289 [63%] with heart failure) over 3 influenza seasons, there were 7154 total vaccinations administered and 5226 (99.4%) participants completed the trial. In the high-dose trivalent vaccine group, there were 975 primary outcome events (883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause) among 884 participants during 3577 participant-seasons (event rate, 45 per 100 patient-years), whereas in the standard-dose quadrivalent vaccine group, there were 924 primary outcome events (846 hospitalizations for cardiovascular or pulmonary causes and 78 deaths from any cause) among 837 participants during 3577 participant-seasons (event rate, 42 per 100 patient-years) (hazard ratio, 1.06 [95% CI, 0.97-1.17]; P = .21). In the high-dose vs standard-dose groups, vaccine-related adverse reactions occurred in 1449 (40.5%) vs 1229 (34.4%) participants and severe adverse reactions occurred in 55 (2.1%) vs 44 (1.7%) participants.
Conclusions and relevance: In patients with high-risk cardiovascular disease, high-dose trivalent inactivated influenza vaccine, compared with standard-dose quadrivalent inactivated influenza vaccine, did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations. Influenza vaccination remains strongly recommended in this population.
Trial registration: ClinicalTrials.gov Identifier: NCT02787044.