Recommended Diuretic Drug Tied to Harmful Side Effects
Patients taking a common diuretic to help lower blood pressure may be better off with a similarly effective but safer one, a new study suggests.
Current guidelines recommend the drug chlorthalidone (Thalitone) as the first-line diuretic. But it can have serious side effects that can be avoided with another diuretic, hydrochlorothiazide (Hydrodiuril), researchers say.
"Diuretics are recognized as among the best drugs to treat hypertension, but there are no randomized studies to help decide which diuretic is best," said lead author Dr. George Hripcsak, head of biomedical informatics at Columbia University in New York City.
Hydrochlorothiazide is the world's most-used diuretic, but chlorthalidone is gaining favor because it is longer acting and, therefore, might be more effective, Hripcsak said.
Guidelines from both the American College of Cardiology and American Heart Association recommend chlorthalidone for that reason.
But the new study found that patients taking chlorthalidone were three times more likely than those taking hydrochlorothiazide to have dangerously low levels of potassium and other electrolyte imbalances, as well as kidney problems.
Six percent of patients taking chlorthalidone had low potassium, compared with 2% of those taking hydrochlorothiazide. The rate remained the same even with lower doses of chlorthalidone, the researchers found.
"If you are taking chlorthalidone, then your physician should be monitoring your electrolytes and kidney function carefully," Hripcsak said.
For the study, his team reviewed 17 years of data on more than 730,000 patients treated for high blood pressure.
While both drugs were equally effective in preventing heart attack and hospitalization for heart failure and stroke, chlorthalidone had a higher risk of side effects, the study found. Those side effects include low potassium, which can trigger abnormal heart rhythms; low salt, which can cause confusion; kidney failure; and type 2 diabetes.
This is not the first study to point out these side effects of chlorthalidone, the study authors said.
"Until stronger evidence comes out to the contrary, I believe this study tips the scales toward hydrochlorothiazide for people taking a diuretic for high blood pressure," said study co-author Dr. Harlan Krumholz, a professor of medicine at Yale University in New Haven, Conn.
Krumholz predicted treatment guidelines might shift from a generic endorsement of chlorthalidone to a more specific statement about the drug that seems safer.
He added that both drugs seem equally effective and are both inexpensive. "The good news is that the better choice is the most commonly prescribed diuretic for hypertension," Krumholz said.
The findings should prompt patients to discuss treatment options with their doctors, he noted.
"The evidence is strong, but it is not a clinical trial, so there remains some uncertainty," Krumholz said. "But until stronger evidence is out, this study represents some of the best information we have -- and it favors hydrochlorothiazide."
Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles, said that because this study looked back at data, it can't prove that one drug is better or safer than the other.
Fortunately, Fonarow said, a large randomized trial comparing these drugs is underway with a plan to enroll 13,500 people with high blood pressure. Results are expected in 2022.
In any case, the most important thing that people with high blood pressure can do is to keep their readings in check, Fonarow said.
"It is critical for individuals with high blood pressure to achieve and maintain recommended blood pressure goals with a well-tolerated medication regimen together with lifestyle modification," he advised.
The report was published online Feb. 17 in JAMA Internal Medicine.
Learn more about high blood pressure from the American Heart Association.
SOURCES: George Hripcsak, M.D., M.S., chairman and professor, department of biomedical informatics, Columbia University, New York City; Harlan Krumholz, M.D., professor of medicine, Yale University, New Haven, Conn.; Gregg Fonarow, M.D., professor of cardiology, University of California, Los Angeles, and director, Ahmanson-UCLA Cardiomyopathy Center; Feb. 17, 2020, JAMA Internal Medicine, online