Quarter-Dose Combo Meds for Hypertension Effective, More Tolerated

Marcia Frellick

June 09, 2017

SYDNEY, AUSTRALIA — Combinations of blood-pressure medications at one-quarter the standard doses can be at least as effective at lowering blood pressure but more easily tolerated than standard-dose monotherapy, suggests a meta-analysis of studies[1].

Two medications combined, each at a quarter dose, were as effective as one usual dose of hypertension medication, the authors found.

Four quarter doses of medications combined was nearly twice as effective as taking one standard dose, according to the study published June 5, 2017 in Hypertension with lead author Dr Alexander Bennett, (George Institute for Global Health, University of New South Wales, Sydney, Australia),

Senior author Dr Anthony Rodgers (George Institute for Global Health) told heartwire from Medscape that his team began this research to try to find a way to lower blood pressure more with fewer side effects.

"All the blood-pressure drug classes that have been launched over the past few decades work by about the same amount," he said. "There's nothing in the pipeline, at least that I'm aware of, that's going to be twice as effective, for example. So we need more tools in hand," as only a third of people on treatment reach blood-pressure goals.

"The side-effects aspect of this is really important for a drug you have to take lifelong," Rodgers said. At standard doses they can include dizziness, insomnia, headache, muscle cramps, and weakness.

This study found that the side effects from single- and dual quarter-dose treatments were about the same as those in the placebo arm and much less than from a standard dose of a single medication. Little information was found on side effects for the quadruple quarter-dose treatment. No trials compared a triple combination dose with placebo.

Previous studies have shown the potential benefit of low-dose hypertension medications, but this is the first systematic review that has looked at the potential of very low doses, according to the authors.

Their meta-analysis included randomized controlled trials with at least one treatment arm involving a quarter-dose therapy and at least one placebo or standard-dose monotherapy. They analyzed 42 studies with 20,284 participants who had high blood pressure and were taking various medications or no medications.

Most of the trials were conducted at least 17 years ago, the authors point out as one of their study's limitations.

An accompanying editorial[2] by Drs Guido Grassi and Giuseppe Mancia (University of Milano-Bicocca, Milan, Italy) discuss some of the other limitations. Among them are that results on quadruple-dose combination treatment are based on a single study with a sample of 18 patients.

Also, treatment duration varied but averaged 7 weeks, "which does not ensure that the favorable blood-pressure effects of low-low dose combination treatment seen in the early treatment phase are maintained over the long term."

They write that it will be important to test the very low doses in home use to see whether the blood-pressure–lowering effects are consistent over 24 hours.

Still, "the quarter-dose treatment strategy deserves to be mentioned among the therapeutic options that are characterized by a good therapeutic efficacy/ tolerability balance, as future hypertension guidelines will likely discuss in their recommendations."

Rodgers acknowledges the short treatment periods and said the team has already begun a yearlong study with 650 patients comparing four quarter doses with optimal guideline care. The hope is for a single pill that combines the very low doses.

George Health Enterprises, the social enterprise arm of the George Institute for Global Health, has applied for patents in this research area, on which Rodgers and a coauthor are named as inventors. George Health Enterprises has also received investment to develop fixed-dose combinations containing aspirin, statins, and blood-pressure–lowering drugs. This work was supported by a National Health and Medical Research Council program grant. Bennett reports no relevant financial relationships.  Rodgers is supported by a National Health and Medical Research Council principal research fellowship. Disclosures for the coauthors are listed in the paper. The editorialists declare no relevant financial relationships.

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