{"doi":"10.1186/s13045-022-01302-7","title":"Hypertension and incident cardiovascular events after next-generation BTKi therapy initiation","abstract":"BACKGROUND: Post-market analyses revealed unanticipated links between first-generation Bruton's tyrosine kinase inhibitor (BTKi) therapy, ibrutinib, and profound early hypertension. Yet, whether this is seen with novel selective second (next)-generation BTKi therapy, acalabrutinib, is unknown. METHODS: Leveraging a large cohort of consecutive B cell cancer patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence and ramifications of new or worsened hypertension [systolic blood pressure (SBP) ≥ 130 mmHg] after acalabrutinib initiation. Secondary endpoints were major cardiovascular events (MACE: arrhythmias, myocardial infarction, stroke, heart failure, cardiac death) and disease progression. Observed incident hypertension rates were compared to Framingham heart-predicted and ibrutinib-related rates. Multivariable regression and survival analysis were used to define factors associated with new/worsened hypertension and MACE, and the relationship between early SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of acalabrutinib-related hypertension was assessed. RESULTS: Overall, from 280 acalabrutinib-treated patients, 48.9% developed new/worsened hypertension over a median of 41 months. The cumulative incidence of new hypertension by 1 year was 53.9%, including 1.7% with high-grade (≥ 3) hypertension. Applying the JNC 8 cutoff BP of ≥ 140/90 mmHg, the observed new hypertension rate was 20.5% at 1 year, > eightfold higher than the Framingham-predicted rate of 2.4% (RR 8.5, P < 0.001), yet 34.1% lower than ibrutinib (12.9 observed-to-expected ratio, P < 0.001). In multivariable regression, prior arrhythmias and Black ancestry were associated with new hypertension (HR 1.63, HR 4.35, P < 0.05). The degree of SBP rise within 1 year of treatment initiation predicted MACE risk (42% HR increase for each + 5 mmHg SBP rise, P < 0.001). No single antihypertensive class prevented worsened acalabrutinib-related hypertension. CONCLUSIONS: Collectively, these data suggest that hypertension may be a class effect of BTKi therapies and precedes major cardiotoxic events.","journal":"Journal of Hematology & Oncology","year":2022,"id":246432,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":883036,"name":"Leylah Azali","orcid":null,"position":1,"is_corresponding":false},{"id":882462,"name":"Lindsay Rosen","orcid":"0000-0002-6121-0082","position":2,"is_corresponding":false},{"id":295281,"name":"Qiuhong Zhao","orcid":"0000-0002-0789-9990","position":3,"is_corresponding":false},{"id":511859,"name":"Tracy Wiczer","orcid":null,"position":4,"is_corresponding":false},{"id":531831,"name":"Marilly Palettas","orcid":"0000-0002-6256-320X","position":5,"is_corresponding":false},{"id":882463,"name":"John Alan Gambril","orcid":"0000-0001-9797-5979","position":6,"is_corresponding":false},{"id":792196,"name":"Onaopepo Kola‐Kehinde","orcid":"0000-0001-9270-0415","position":7,"is_corresponding":false},{"id":792642,"name":"Patrick Ruz","orcid":null,"position":8,"is_corresponding":false},{"id":882464,"name":"Sujay Kalathoor","orcid":"0000-0003-4910-3433","position":9,"is_corresponding":false},{"id":278927,"name":"Kerry A. Rogers","orcid":"0000-0001-5748-7874","position":10,"is_corresponding":false},{"id":767147,"name":"Adam S. Kittai","orcid":"0000-0002-4891-6144","position":11,"is_corresponding":false},{"id":35685,"name":"Michael R. Grever","orcid":"0000-0002-1605-7875","position":12,"is_corresponding":false},{"id":278931,"name":"Farrukh T. Awan","orcid":"0000-0003-1813-9812","position":13,"is_corresponding":false},{"id":35686,"name":"John C. Byrd","orcid":"0000-0001-9830-0711","position":14,"is_corresponding":false},{"id":245731,"name":"Jennifer A. Woyach","orcid":"0000-0002-3403-9144","position":15,"is_corresponding":false},{"id":278932,"name":"Seema A. Bhat","orcid":"0000-0001-7844-0856","position":16,"is_corresponding":false},{"id":430239,"name":"Daniel Addison","orcid":"0000-0002-9113-8333","position":17,"is_corresponding":false},{"id":882461,"name":"Sunnia T. Chen","orcid":"0000-0001-6914-510X","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35836241","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":[]}