{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:32:16Z","timestamp":1789086736486,"version":"build-2803163510"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The discovery of driver mutations has transformed advanced non\u2013small cell lung cancer treatment, with ALK (anaplastic lymphoma kinase)\u2013rearranged patients achieving longest overall survival. However, the risk of cancer therapy\u2013related cardiovascular diseases (CTRCVDs) is underrecognized, particularly comparing second\u2010generation ALK\u2013tyrosine kinase inhibitors alectinib and brigatinib to the third\u2010generation tyrosine kinase inhibitor lorlatinib, which offers the longest progression\u2010free survival. We aimed to compare CTRCVDs risks among patients with lung cancer receiving ALK\u2010tyrosine kinase inhibitor, assess incidence trends, and identify clinical risk factors associated with ALK\u2010tyrosine kinase inhibitor\u2010related CTRCVDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">This retrospective cohort study of 946\u2009848 adults with lung cancer (2010\u20132024) using TriNetX compared CTRCVDs risk in ALK\u2010mutated patients treated with lorlatinib versus brigatinib\/alectinib. After excluding ROS1\u2010mutated cases and 1:1 propensity score matching, 744 patients per group were analyzed. CTRCVDs, defined as myocardial infarction, stroke, arterial embolism, or heart failure, were evaluated with Kaplan\u2013Meier analysis and Cox proportional hazards models over 2\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Lorlatinib treatment was associated with a significantly increased risk of CTRCVDs (hazard ratio [HR], 3.00 [95% CI, 1.65\u20135.45];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001). Incidence rose from 2.2% at 6 months to 6.6% at 3\u2009years, versus 1.7% and 2.2% in the brigatinib\/alectinib cohort. Multivariable analysis identified advanced age (HR, 1.02 [95% CI, 1.00\u20131.04];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.04), atrial fibrillation\/flutter history (HR, 2.39 [95% CI, 1.13\u20135.07];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.002), and lorlatinib use (HR, 2.42 [95% CI, 1.57\u20133.72];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001) as independent predictors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p xml:lang=\"en\">These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.<\/jats:p>\n                  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