A combination of drugs for high blood pressure that included a calcium-channel blocker was more effective at preventing heart problems in patients than a recommended regimen containing a diuretic, or water pill, researchers have found in a large clinical trial.
The trial compared two pills, each containing two drugs used to lower blood pressure. Patients taking pills that combined an ACE inhibitor with a calcium-channel blocker suffered 20 percent fewer heart attacks, strokes, heart procedures and deaths than those taking an ACE inhibitor with a diuretic, the investigators found.
The study was funded by Novartis, which makes both of the two-in-one pill treatments evaluated, and published in Thursday’s issue of The New England Journal of Medicine.
The findings raise questions about treatment guidelines developed by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, the researchers said.
The guidelines recommend starting treatment for high blood pressure with a single pill, preferably a diuretic, and then adding other drugs if necessary. (Many patients cannot control their blood pressure with just one medicine.)
“The important message is that the government recommends a drug that provides 20 percent less benefit than we found” in an alternate therapy, said Dr. Kenneth Jamerson, lead author of the study and a professor of internal medicine at University of Michigan Medical School.
The appropriate use of inexpensive diuretics has been a focus of controversy among experts. In 2002, one of the largest federally funded clinical trials concluded that diuretics were the safest and most cost-effective therapy for high blood pressure when compared to an ACE inhibitor, a calcium-channel blocker and an alpha blocker.
The latest randomized, double-blinded study included 11,506 participants in the United States and four other countries. The subjects’ mean age was 68. Sixty percent had diabetes, and all were at risk for serious cardiovascular problems.
Some 5,744 patients were assigned to take benazepril with amlodipine (the ACE inhibiter and a calcium-channel blocker combination), while 5,762 took benazepril with hydrochlorothiazide (an ACE inhibiter and a diuretic).
Within six months, 73 percent of patients treated with either two-in-one pill were able to lower their blood pressure into a safe range, the researchers found. By the end of the three-year trial, 80 percent of participants had their blood pressure under control.
Among patients taking the pill containing a diuretic, however, 11.8 percent suffered a serious cardiovascular event, compared to 9.6 percent of those taking the pill with the calcium-channel blocker, representing an absolute difference of 2.2 percent and a relative risk reduction of 19.6 percent with the calcium-channel blocker.
The researchers judged the disparity sufficient to halt the trial early, so as to give subjects the option of continuing on the more effective therapy.
An editorial accompanying the study called for a reexamination of current treatment guidelines for high blood pressure and their emphasis on thiazide-type diuretics as a first-line therapy. The guidelines should be more flexible, the editorial said.
Dr. Aram Chobanian, a professor of medicine and pharmacology at Boston University School of Medicine and author of the editorial, said he had questions about whether the diuretic was used appropriately in this trial, adding that a single trial is “not enough to recommend that everyone be on a calcium-channel blocker and an ACE inhibitor.”
He said several other clinical trials have reported positive results regarding the combined use of a diuretic and ACE inhibitor, “so we don’t want to damn that combination.”
“The most important thing in treatment is to get blood pressure down, and how you do it becomes less important,” Dr. Chobanian added.
An expert panel will review the evidence and update treatment guidelines, which are expected to be available for public review in early 2009, with a final version to be published in the spring of 2010, a spokeswoman for the National Heart, Lung, and Blood Institute said.
