The drug has been linked to heart problems before. It’s associated with serious and potentially fatal heart rhythm problems, especially in people who have an increased risk for heart disease, according to prescribing information on the drug’s label. And 12 percent of people taking ibrutinib in clinical trials developed high blood pressure, the drug label warns. But the current study found a much bigger risk of heart problems: Seventy-eight percent of people developed new high blood pressure or saw preexisting hypertension get worse when they took ibrutinib. And people taking ibrutinib who developed new or worsened hypertension were more than twice as likely to develop other heart problems, including heart rhythm disorders like atrial fibrillation. “We knew that ibrutinib was associated with a greater than sixfold increased chance of abnormal heart rhythms, including uncommon but potentially life-threatening rhythms,” says Daniel Addison, MD, the senior author of the study and the codirector of the cardio-oncology program at the Ohio State University Wexner Medical Center. “However, this study establishes that hypertension is common after starting Ibrutinib,” Dr. Addison says. “It also suggests that hypertension may be tied to the patient’s chance of developing other heart issues during use of ibrutinib.” Because of previously known hypertension risks with the drug, doctors already tend to closely monitor blood pressure for patients taking ibrutinib, Addison says. But the results suggest that they may need to monitor patients more closely. Blood pressure medicines do appear to help patients on ibrutinib. Taking drugs to lower blood pressure was associated with a 60 percent reduction in major cardiac events like heart attacks and strokes among patients using the cancer therapy. Generally, this suggests that most patients on ibrutinib would be able to continue with therapy despite the hypertension risks, Addison says. For the study, researchers examined medical records for 562 consecutive patients treated with ibrutinib for lymphomas and leukemias at Ohio State University’s comprehensive cancer center between 2009 and 2016. Patients were 64 years old on average; most were male and had a form of blood cancer known as chronic lymphocytic leukemia. To assess blood pressure risks associated with treatment, researchers looked at how many people developed new cases of hypertension, or blood pressure at or above 130/80 mmHg, the threshold set in the 2017 guidelines from the American College of Cardiology and the American Heart Association. Almost 54 percent of patients who had normal blood pressure at the start of the study developed hypertension within six months of starting ibrutinib, the study found. After a median follow-up period of 30 months, 72 percent of people who started out with healthy blood pressure had developed hypertension. And 18 percent of these new hypertension cases involved blood pressure readings that climbed above 160/100 mmHg. In addition, 82 percent of the patients who had hypertension when they started on ibrutinib developed worse blood pressure while they were on the cancer treatment. The study wasn’t a controlled experiment designed to prove whether or how ibrutinib might cause high blood pressure, heart rhythm problems, or other cardiac issues. The study results also use a newer, lower threshold for diagnosing hypertension than was in place for pivotal clinical trials used to win U.S. marketing approval for ibrutinib; under previous hypertension guidelines, this condition wasn’t diagnosed until blood pressure reached 140/90 mmHg. “The difference in the incidence of high blood pressure in this study compared to older studies can be possibly attributable to the difference in the definition of high blood pressure,” says Peter Kim, MD, the medical director of cardiac monitoring at the University of Texas MD Anderson Cancer Center. “Whereas previous studies generally used a systolic blood pressure of 140 mmHg as the cutoff, this study set a lower cutoff of 130 mmHg, which would have likely included more cases of hypertension,” Dr. Kim says. Cardiovascular complications were more than twice as common among ibrutinib patients who did experience worsened blood pressure — this happened in about 19 percent of people whose blood pressure rose, and roughly 8 percent of people whose blood pressure didn’t climb. Complications included atrial fibrillation and other rhythm disorders, heart attack, stroke, heart failure, and sudden cardiac death. Ibrutinib works by blocking a protein in B cells called Bruton’s tyrosine kinase. Unchecked, this protein can help cancer cells multiply and survive. Ibrutinib is approved to treat several types of blood cancers. Pharmacyclics, part of AbbVie, and Janssen, part of Johnson & Johnson, market ibrutinib in the United States. The companies declined to comment on the findings of the study. In a joint statement, the companies said that hypertension is among the side effects listed on the drug label and that routine blood pressure monitoring is already recommended with the drug. “It is important to emphasize that this is a lifesaving therapy with dramatic cancer treatment benefits, including improved survival,” Addison says. “We need to find the best ways to manage high blood pressure and protect against other heart-related issues.” Several authors on the ibrutinib study disclosed financial ties to drug companies, including AbbVie, Pharmacyclics, and Janssen as well as makers of competing cancer medicines in the same family of medicines as ibrutinib and makers of blood pressure drugs.
