Combining low doses of several different blood pressure drugs may be better than using a standard dose of just one medication, a new review of past studies suggests.
Two-thirds of patients taking a blood pressure-lowering drug don’t improve as much as their doctors would like, the researchers noted.
Citing a “critical need” for new approaches, they reviewed 42 studies involving ultra-low doses of multiple medications.
Their conclusion: “Low doses can achieve large effects when used in combination,” said review co-author Dr. Anthony Rodgers. “What we found was that four quarter doses [of different medications] gives a lot of benefit with few apparent side effects.”
High blood pressure is a leading cause of stroke, heart attack and several other major conditions, so it’s important to get good treatment, said Rodgers. He is a professor of global health at the George Institute for Global Health and University of New South Wales, in Australia.
However, “all blood pressure medications have only moderate effects when used alone, and many have side effects when used at higher doses,” he added.
Cardiologist Dr. Eugene Yang said blood pressure medications seem to work better when they’re combined.
“There seems to be a synergetic effect between two kinds of drugs,” said Yang, who wasn’t involved in the study.
Combinations of ultra-low doses of existing drugs are “certainly something to think about,” added Yang, a professor at the University of Washington, in Seattle. Already, some combo blood pressure drugs are available in the United States, according to background notes in the study.
But Yang cautioned that much more research is needed. “You really need to do larger studies with more patients that follow them for much longer,” he said. Patients in the new meta-analysis were tracked for two weeks at most, he noted.
Study co-author Rodgers agreed. “More long-term research is needed, and new combinations need to be manufactured, before triple or quadruple combinations are ready for clinical use in the U.S.,” he said.
About one out of three U.S. adults has high blood pressure, according to the U.S. Centers for Disease Control and Prevention.
In this new study, almost 20,300 adults had high blood pressure. Participants were taking different types of blood pressure medications, including ACE inhibitors, angiotensin receptor blockers, beta blockers, thiazides and calcium channel blockers.
According to the researchers, combining quarter doses of two drugs was as effective as a single standard dose of one blood pressure-lowering medication.
Even better, a combination of four medications—each at one-quarter dose—was nearly twice as effective as one drug at the standard dose, they found.
“A quarter dose gives about half as much benefit, which is not a lot by itself, but still something, with little or no side effects,” Rodgers said.
In general, all of the quarter-dose combinations reduced systolic and diastolic blood pressure (the upper and lower numbers in a blood pressure reading) by several points compared to a placebo.
One study of quarter doses of four medications combined found that that combination reduced systolic blood pressure by 22 points and diastolic by 13 points, on average, compared to a placebo, the researchers reported.
Little information was provided on side effects for the four-drug combo. But side effects for the other quarter-dose therapies were far less than those seen with a standard dose of one blood pressure-lowering medication, the researchers said.
Yang pointed out that the research has limitations. Most of the studies ended more than 17 years ago, he said. He also noted that several of the authors have received funding from drug makers. Also, two of the authors, including Rodgers, are listed as inventors on patent applications related to this area of research.
The study was published online in the journal Hypertension.