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Yet, whether this is seen with novel selective second (next)-generation BTKi therapy, acalabrutinib, is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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)\u2009\u2265\u2009130\u00a0mmHg] 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, from 280 acalabrutinib-treated patients, 48.9% developed new\/worsened hypertension over a median of 41\u00a0months. The cumulative incidence of new hypertension by 1 year was 53.9%, including 1.7% with high-grade (\u2265\u20093) hypertension. Applying the JNC 8 cutoff BP of\u2009\u2265\u2009140\/90\u00a0mmHg, the observed new hypertension rate was 20.5% at 1\u00a0year,\u2009&gt;\u2009eightfold higher than the Framingham-predicted rate of 2.4% (RR 8.5,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), yet 34.1% lower than ibrutinib (12.9 observed-to-expected ratio,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). In multivariable regression, prior arrhythmias and Black ancestry were associated with new hypertension (HR 1.63, HR 4.35,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). The degree of SBP rise within 1\u00a0year of treatment initiation predicted MACE risk (42% HR increase for each\u2009+\u20095\u00a0mmHg SBP rise,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). No single antihypertensive class prevented worsened acalabrutinib-related hypertension.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, these data suggest that hypertension may be a class effect of BTKi therapies and precedes major cardiotoxic events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13045-022-01302-7","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T05:05:04Z","timestamp":1657775104000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Hypertension and incident cardiovascular events after next-generation BTKi therapy initiation"],"prefix":"10.1186","volume":"15","author":[{"given":"Sunnia T.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leylah","family":"Azali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Wiczer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilly","family":"Palettas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gambril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onaopepo","family":"Kola-Kehinde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujay","family":"Kalathoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kittai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrukh","family":"Awan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Woyach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema A.","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Addison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"issue":"4","key":"1302_CR1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1056\/NEJMoa1509981","volume":"374","author":"JC Byrd","year":"2016","unstructured":"Byrd JC, Harrington B, O\u2019Brien S, Jones JA, Schuh A, Devereux S, et al. 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JCB has received research and has consulted for Acerta Pharma and Pharmacyclics, Inc. FA has received research funding from Innate Pharma and Pharmacyclics and provided consulting services to Gilead Sciences, Pharmacyclics, Inc., Janssen, Abbvie, Sunesis, AstraZeneca, Genentech, and Novartis Oncology, and served on the speakers bureau of Abbvie and AstraZeneca. KR received research funding from Genentech and participated in an advisor board for Acerta Pharma. AK has provided consulting services for Abbvie, Beigene, Bristol Myers Squibb, and Janssen. MG has provided consulting services for Ascerta and Pharmacyclics. JW received research funding from Abbvie, Pharmacyclics, Janssen, Acerta, Loxo, Karyopharm, and Morphosys and has consulted for Janssen and Pharmacyclics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"92"}}