{"doi":"10.1001/jamanetworkopen.2023.31284","title":"Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease","abstract":"Importance: Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial. Objective: To evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity. Design, Setting, and Participants: This study was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over 3 consecutive influenza seasons from September 2016 to July 2019. Follow-up was completed in July 2019, and data were analyzed from September 21, 2016, to July 31, 2019. Weekly Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity was ascertained to assess the weekly odds of the primary outcome. The study population included 3094 patients with high-risk CV disease from participating centers in the US. Intervention: Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for up to 3 seasons. Main Outcomes and Measures: The primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Additional measures included weekly CDC-reported ILI activity data by state. Results: Among 3094 participants (mean [SD] age, 65 [12] years; 2309 male [75%]), we analyzed 129 285 person-weeks of enrollment, including 1396 composite primary outcome events (1278 CP hospitalization, 118 deaths). A 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < .001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < .001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = .001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors. Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > .99). High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = .43). Traditionally warmer months in the US were associated with lower CV risk independent of local ILI activity. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. Other seasonal factors may play a role in the coincident high rates of ILI and CV events. Trial Registration: ClinicalTrials.gov Identifier: NCT02787044.","journal":"JAMA Network Open","year":2023,"id":354191,"datarank":0.3423761422288524,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.030459910976876937,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.030459910976876937,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":5,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02787044"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28286,"name":"Brian Claggett","orcid":"0000-0002-4215-9218","position":1,"is_corresponding":false},{"id":266923,"name":"Jacob A. Udell","orcid":"0000-0001-7402-9584","position":2,"is_corresponding":false},{"id":266922,"name":"KyungMann Kim","orcid":"0000-0002-6726-003X","position":3,"is_corresponding":false},{"id":266924,"name":"Jacob Joseph","orcid":"0000-0002-7279-4896","position":4,"is_corresponding":false},{"id":227543,"name":"Michael E. Farkouh","orcid":"0000-0002-8095-0246","position":5,"is_corresponding":false},{"id":916315,"name":"Alexander Peikert","orcid":"0000-0003-0947-5865","position":6,"is_corresponding":false},{"id":231417,"name":"Ankeet S. Bhatt","orcid":"0000-0002-6449-4535","position":7,"is_corresponding":false},{"id":266926,"name":"Matthew C. Tattersall","orcid":"0000-0002-6115-9651","position":8,"is_corresponding":false},{"id":3774,"name":"Deepak L. Bhatt","orcid":"0000-0002-1278-6245","position":9,"is_corresponding":false},{"id":266932,"name":"Lawton S. Cooper","orcid":"0000-0002-9704-8777","position":10,"is_corresponding":false},{"id":27970,"name":"Scott D. Solomon","orcid":"0000-0003-3698-9597","position":11,"is_corresponding":false},{"id":260473,"name":"Orly Vardeny","orcid":"0000-0002-6387-1351","position":12,"is_corresponding":false},{"id":266925,"name":"Sheila M. Hegde","orcid":"0000-0001-8157-8899","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T01:13:06.959762Z","pmid":"37707817","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}