Better therapy persistence seen with separate antihypertensives than single fixed-dose combinations

Study finds that patients taking antihypertensives as two separate pills have a higher chance of continuing treatment for longer than those taking a single fixed-dose combination.

Blood pressure check

Patients who take antihypertensive treatment as separate pills are more likely to continue the therapy than those who take it as a single fixed-dose combination, a study shows.

Thomas Grimmsmann, from the University Medicine Greifswald, Germany, and Wolfgang Himmel, from the University Medical Center, Göttingen, Germany, examined data for 8,032 patients who were prescribed a new antihypertensive treatment between 2007 and 2008 and who were followed up at yearly intervals for four years.

They set out to discover if patients’ “persistence rates” — the number of patients who continued their treatment for the prescribed duration — was any different if treatment was taken as monotherapy, as a single fixed-dose combination pill containing two drugs, or as a “free-drug” combination, which the researchers defined as two separate pills.

The researchers report in BMJ Open
 (online, 22 November 2016) that persistence rates at four years were almost identical for patients who began monotherapy and those who took a fixed combination therapy (40.3% versus 39.8%). But the persistence rate was higher, at 54.4%, for patients who started their antihypertensive therapy as a free-drug combination, made up of two different pills (odds ratio 2.00 for free compared with fixed combinations, 95% confidence interval 1.6–2.5; P<0.0001).

“The feeling of being free to experiment with individual drugs, including the possibility of taking both drugs or cancelling drugs, may correspond to a more responsible role of the patient as his or her own health agent, which may be associated with improved drug persistence,” the researchers suggest. “Considering patient behaviour, simple drug regimens consisting of only one pill with fixed-dose combinations may not represent the most attractive regimens or achieve the best persistence.”

They team suggests that future research should focus on patient attitudes towards different drug regimens.

Mike Knapton, associate medical director at the British Heart Foundation, a charity based in London, says people who are newly diagnosed with hypertension are typically prescribed more than one drug and it is “perceived wisdom” that it is easier for patients to take these drugs as a single combination. “This research challenges that,” he says.

Patients may stop taking their drugs in the first few weeks if they experience side effects, explains Knapton. For single, fixed-dose combination therapies, it is difficult to know which drug is causing the problems – something that is more easily detected when drugs are given as separate drugs, he adds.

“If I was going to start somebody off on antihypertensive therapy I would begin on a single therapy and see if that controls it then, if necessary, add another drug,” he says. “If that works for them then I would look for a combination drug, which is made up of the two single drugs.

“That may be more complicated than putting them on a combination therapy at the outset but this research suggests that that might be the better strategy for some patients.”


[1] Grimmsmann T & Himmel W. Comparison of therapy persistence for fixed versus free combination antihypertensives: a retrospective cohort study. BMJ Open 2016;6:e011650. doi: 10.1136/bmjopen-2016-011650

Last updated
The Pharmaceutical Journal, Better therapy persistence seen with separate antihypertensives than single fixed-dose combinations;Online:DOI:10.1211/PJ.2016.20202063

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