Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK), which is an integral component of the B-cell receptor (BCR) and cytokine (CYK) pathways. Ibrutinib is approved by the US Food and Drug Administration for use in multiple B-cell related conditions including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenstrm macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease (cGVHD).1 Ibrutinib use has been associated with multiple adverse events (AEs), of which cardiovascular (CV) toxicity represents one of the most commonly studied.
The exact pathophysiology to explain the CV risks associated with ibrutinib have not yet been fully elucidated, although several mechanisms have been proposed. Ibrutinib has been shown to inhibit the phosphoinositide 3-kinase (PI3K)/Akt pathway, which could lead to increased vascular tissue fibrosis and cellular remodeling.2 Additional mechanisms include VEGF downregulation, decreased nitric oxide, and promotion of endothelial cell dysfunction.
According to the prescribing information (PI) for the medication, potential CV toxicities include cardiac arrhythmias such as ventricular tachyarrhythmias (grade 3 or higher in 0.2% of patients) and atrial fibrillation (grade 3 or higher in 4% of patients). Hypertension (HTN) of any grade was reported in 12% of patients in clinical trials with grade 3 or higher events occurring in 5% of patients, with a median time to onset of approximately 6 months.
Despite these reported numbers in the PI, multiple postmarketing studies have pointed to higher percentages of CV-associated AEs.
To further clarify the real-world CV risk associated with ibrutinib, a group of authors led by Dickerson and colleagues recently published a study evaluating the incidence of new or worsened HTN along with the relationship of HTN with developing incident major adverse cardiovascular events (MACE) including arrhythmias, acute myocardial infarction (AMI), cerebrovascular accident (CVA), heart failure, and CV death.3
The authors retrospectively evaluated 562 adult patients with lymphoid malignancies treated with ibrutinib at a single center at Ohio State University between 2009 and 2016. New HTN was defined as a systolic blood pressure (SBP) of 130 mmHg or higher on 2 separate visits within 3 months. Worsened HTN was diagnosed by an increase in the grade of HTN according to the Common Terminology Criteria for Adverse Events (CTCAE) or an increase in the patients anti-HTN medications. Baseline HTN was defined as SBP of 130 mmHg or higher on 2 visits within 3 months prior to starting ibrutinib or a reported history of HTN with current use of at least 1 anti-HTN medication.
Most patients were diagnosed with CLL (73.8%) and were administered ibrutinib for relapsed disease. And, 62% of patients had a diagnosis of HTN at the time ibrutinib was started, of which 63% were receiving at least 1 anti-HTN medication.
Read the original post:
Ibrutinib and Hypertension in CLL: What Are the Risks? - Cancer Therapy Advisor
- Cardiac MR PET CT Program - Massachusetts General Hospital, Boston, MA - April 12th, 2018 [April 12th, 2018]
- The History, Physical Examination, and Cardiac ... - April 21st, 2018 [April 21st, 2018]
- Dor procedure - Wikipedia - April 26th, 2018 [April 26th, 2018]
- Cardiac Remodeling and Its Significance - Verywell - May 13th, 2018 [May 13th, 2018]
- AndrewMcCulloch - Cardiac Mechanics Research Group - May 30th, 2018 [May 30th, 2018]
- Cardiology Conferences | Cardiac Nursing Events ... - June 3rd, 2018 [June 3rd, 2018]
- Cardiac MR PET CT Program - Massachusetts General Hospital ... - June 5th, 2018 [June 5th, 2018]
- Cardiac resynchronization therapy - Wikipedia - June 23rd, 2018 [June 23rd, 2018]
- Cardiac Remodeling and Its Significance - verywellhealth.com - October 5th, 2018 [October 5th, 2018]
- Ventricular remodeling - Wikipedia - December 21st, 2018 [December 21st, 2018]
- The Significance of Cardiac Remodeling - verywellhealth.com - December 21st, 2018 [December 21st, 2018]
- Ventricular hypertrophy - Wikipedia - December 26th, 2018 [December 26th, 2018]
- Cardiac remodelingconcepts and clinical implications: a ... - April 3rd, 2019 [April 3rd, 2019]
- Emerging roles of proteoglycans in cardiac remodeling ... - May 23rd, 2019 [May 23rd, 2019]
- Antibody could fine-tune recovery from heart attack - Futurity: Research News - September 27th, 2019 [September 27th, 2019]
- What are the respiratory effects of e-cigarettes? - The BMJ - October 3rd, 2019 [October 3rd, 2019]
- AI Pinpoints Genes Associated With Heart Failure - Forbes - October 3rd, 2019 [October 3rd, 2019]
- PH Common in Myeloproliferative Neoplasms, Linked to Diastolic Dysfunction - The Cardiology Advisor - October 26th, 2019 [October 26th, 2019]
- Effects of genetic transfection on calcium cycling pathways mediated by double-stranded adeno-associated virus in postinfarction remodeling - DocWire... - November 6th, 2019 [November 6th, 2019]
- Angion Presents Data on the Impact and Burden of Delayed Graft Function at the American Society of Nephrology Kidney Week 2019 - GlobeNewswire - November 15th, 2019 [November 15th, 2019]
- Stealth BioTherapeutics Reports Third Quarter 2019 Financial Results And Recent Business Highlights - P&T Community - November 15th, 2019 [November 15th, 2019]
- What's being done to close the research gap when it comes to men's and women's cardiac health - The Loop - November 23rd, 2019 [November 23rd, 2019]
- Heart Ventricle Remodeling - an overview | ScienceDirect ... - November 26th, 2019 [November 26th, 2019]
- Denise Merkl, 1949-2019 The Times-Independent - The Times-Independent - December 16th, 2019 [December 16th, 2019]
- Is There a Future for CAR T-Cell Therapy in Heart Failure? - AJMC.com Managed Markets Network - December 16th, 2019 [December 16th, 2019]
- $13 Million Grant to Probe the Genome of Heart Cells - PRNewswire - December 18th, 2019 [December 18th, 2019]
- TransThera Biosciences Announces IND Approval from FDA for Clinical Studies of TT-00920 to Treat Chronic Heart Failure - BioSpace - December 18th, 2019 [December 18th, 2019]
- News - Michigan Lawmaker to Offer CON Reforms - The Heartland Institute - December 28th, 2019 [December 28th, 2019]
- Personalized Medicine for AFib: How Electric Activity in the Heart Can Predict Individual Progression of Atrial Fibrillation - DocWire News - December 28th, 2019 [December 28th, 2019]
- Cardiac Restoration Systems Market Drives, Emerging Trends, Key Value And Forecast 2025 - Industry Mirror - December 31st, 2019 [December 31st, 2019]
- New Living Machines Are Created in the Lab - Tufts Now - January 16th, 2020 [January 16th, 2020]
- Man thinks sepsis was a cold and loses his leg on his 40th birthday - Information-Analytic Agency NEWS.am - January 25th, 2020 [January 25th, 2020]
- Could Colchicine Be the New Aspirin? - Medscape - January 28th, 2020 [January 28th, 2020]
- Coronary Microvascular Dysfunction Found to Increase Risk for CV Events in Chronic Kidney Disease - Renal and Urology News - January 28th, 2020 [January 28th, 2020]
- Link between chronic kidney disease and heart failure is identified in patients - UAB News - February 9th, 2020 [February 9th, 2020]
- Advancing an oral drug for pulmonary arterial hypertension - Penn: Office of University Communications - February 15th, 2020 [February 15th, 2020]
- MR Improves in Half of Low-Flow/Low-Gradient AS Patients Undergoing TAVR - TCTMD - February 15th, 2020 [February 15th, 2020]
- Varied Nightly Bedtime, Sleep Duration Linked to CVD Risk - Medscape - March 4th, 2020 [March 4th, 2020]
- BioVentrix Announces Ralph Stephan von Bardeleben, MD, as Co- Principal Investigator of the REVIVE-HF Clinical Trial - Business Wire - March 4th, 2020 [March 4th, 2020]
- Slump in Production of Absorbable Heart Stent Amidst Covid-19 Outbreak to Diminish Prospects of Sales - Jewish Life News - May 7th, 2020 [May 7th, 2020]
- Cardiol Therapeutics files patent to use CBD therapies for patients with coronavirus - Proactive Investors USA & Canada - May 7th, 2020 [May 7th, 2020]
- The Effector Cells and Cellular Mediators of Immune System Involved in Cardiac Inflammation and Fibrosis after Myocardial Infarction - DocWire News - May 7th, 2020 [May 7th, 2020]
- Cardiac Restoration Systems Market Detailed Analysis and Forecast 2018-2028 3w Market News Reports - 3rd Watch News - May 16th, 2020 [May 16th, 2020]
- LV Mass Regression After TAVR Linked to Better Long-term Outcomes - TCTMD - May 16th, 2020 [May 16th, 2020]
- Hypoxic Training Equipment Industry to 2026; Featuring Profiles of Biomedtech Australia, Go2 Altitude, Gooxygen, Higher Peak, and More - GlobeNewswire - May 16th, 2020 [May 16th, 2020]
- Surplus antioxidants are pathogenic for hearts and skeletal muscle - The Mix - May 16th, 2020 [May 16th, 2020]
- $125619 awarded in spring Community Needs Grants - The MidWeek - May 20th, 2020 [May 20th, 2020]
- Absorbable Cardiac Stent Market 2020-2026 Growth Trends, Leading Players, Competitive Strategies and 2026 Future Prospect - Cole of Duty - June 15th, 2020 [June 15th, 2020]
- The Protective Effects of Liguzinediol on Congestive Heart Failure Induced by Myocardial Infarction and Its Relative Mechanism - DocWire News - June 19th, 2020 [June 19th, 2020]
- ABSORBABLE HEART STENT Sales Market 2020-2026: Analysis by Growth Factors, Key Trends and Competitive Strategies - Cole of Duty - June 19th, 2020 [June 19th, 2020]
- Absorbable Heart Stent Market 2020: Potential growth, attractive valuation make it is a long-term investment | Know the COVID19 Impact | Top Players:... - June 19th, 2020 [June 19th, 2020]
- Microneedle-mediated gene delivery for the treatment of ischemic myocardial disease - Science Advances - June 19th, 2020 [June 19th, 2020]
- Worldwide Comprehensive Review of Absorbable Cardiac Stent Market Trends and Its Development - 3rd Watch News - June 22nd, 2020 [June 22nd, 2020]
- Absorbable Heart Stent Market In-deep Analysis And Experts Review Report 2020-2026 - Cole of Duty - June 22nd, 2020 [June 22nd, 2020]
- Elixir Medical Announces Outstanding 12-Month Data for DynamX Coronary Bioadaptor System, Demonstrating No Target Vessel Revascularization, No... - July 1st, 2020 [July 1st, 2020]
- Cardiac Restoration Systems Market Analysis with Key Players, Applications, Trends and Forecast to 2027 - Jewish Life News - July 1st, 2020 [July 1st, 2020]
- Women Thrive on Baroreflex Activation for Heart Failure - Medscape - July 1st, 2020 [July 1st, 2020]
- Meet Inspiring young Doctor from Gallipolis, Ohio USA: Dr Wilton Triggs II - International Business Times, Singapore Edition - August 19th, 2020 [August 19th, 2020]
- Absorbable Heart Stent Market Research 2020-Competitive Insights: Abbott Laboratories, Biotronik, Arterial Remodeling Technologies, Amaranth Medica -... - August 19th, 2020 [August 19th, 2020]
- Novel mechanism connects SPEG, RyR2 and atrial fibrillation - Baylor College of Medicine News - August 19th, 2020 [August 19th, 2020]
- Comprehensive Analysis On Absorbable Heart Stent Market Insights Abbott Laboratories, Biotronik, Arterial Remodeling Technologies, Amaranth Medica -... - August 28th, 2020 [August 28th, 2020]
- Lincolnton man wrestles with COVID and wins | News - Lincoln Times-News - August 28th, 2020 [August 28th, 2020]
- Impact of sex on timing and clinical outcome of septal myectomy for obstructive hypertrophic cardiomyopathy - DocWire News - August 28th, 2020 [August 28th, 2020]
- Adverse Remodeling in Atrial Fibrillation Following Isolated Aortic Valve Replacement Surgery - DocWire News - August 28th, 2020 [August 28th, 2020]
- EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice - DocWire News - August 28th, 2020 [August 28th, 2020]
- Business Notebook: Several 'pro-business' laws now in effect; SEMO joins forces with Codefi - Southeast Missourian - August 31st, 2020 [August 31st, 2020]
- Global Absorbable Heart Stent Market Covid-19 Impact Analysis, Leading Player, Application, New Product Developments and 2024 Forecast - The Daily... - August 31st, 2020 [August 31st, 2020]
- Pulmonary Hypertension in HFpEF and HFrEF: JACC Review Topic of the Week - DocWire News - August 31st, 2020 [August 31st, 2020]
- Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in myofibroblast differentiation - Science... - September 15th, 2020 [September 15th, 2020]
- 3D curvature-instructed endothelial flow response and tissue vascularization - Science Advances - September 19th, 2020 [September 19th, 2020]
- FUNDC1 interacts with FBXL2 to govern mitochondrial integrity and cardiac function through an IP3R3-dependent manner in obesity - Science Advances - September 19th, 2020 [September 19th, 2020]
- Denervation Therapy Ventures Where Drugs Have Failed: HFpEF - Medscape - October 14th, 2020 [October 14th, 2020]
- Comprehensive Report on Absorbable Heart Stent Market 2020 | Size, Growth, Demand, Opportunities & Forecast To 2026 | Impact Of Covid 19 Analysis... - November 26th, 2020 [November 26th, 2020]
- Machine learning integration of circulating and imaging biomarkers for explainable patient-specific prediction of cardiac events: A prospective study... - November 26th, 2020 [November 26th, 2020]
- NeuBase Therapeutics Announces Positive Preclinical In Vivo Data for PATrOL-enabled Anti-gene for the Treatment of Myotonic Dystrophy Type 1 -... - December 17th, 2020 [December 17th, 2020]
- Elite Soccer Players Have Big Hearts and That's Okay - Medscape - December 20th, 2020 [December 20th, 2020]
- A high triglyceride-glucose index is associated with left ventricular dysfunction and atherosclerosis - DocWire News - January 20th, 2021 [January 20th, 2021]
- Elixir Medical Announces First Patient Treated in BIOADAPTOR Randomized Controlled Trial of DynamX Coronary Bioadaptor System - Business Wire - January 20th, 2021 [January 20th, 2021]
- Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis - DocWire... - January 20th, 2021 [January 20th, 2021]
- Global Absorbable Heart Stent Market Development Factors 2020 Overview by Regional Analysis, Industry Size, Business Share, Growth Rate Forecast to... - January 31st, 2021 [January 31st, 2021]