LEICESTER, UK — The number and class of blood-pressure–lowering drugs are risk factors for nonadherence to therapy for hypertension, according to a new study in hypertensive patients notable because their nonadherence was biochemically confirmed[1].
The study, published in the June 2017 issue of Hypertension, found that the risk of nonadherence increased more than 75% with every increment in number of prescribed antihypertensive drugs and that nonadherence to diuretics was higher than to other classes of antihypertensive medications.
“Nonadherence to blood-pressure–lowering therapy is highly prevalent, especially among patients on multiple drugs or diuretics,” senior author Dr Maciej Tomaszewski (University of Manchester, UK), told heartwire from Medscape.
The findings also highlight the importance of biochemically testing for the presence of prescribed antihypertensive in blood or urine samples. The researchers used high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) of urine and serum to screen for nonadherence to most commonly prescribed antihypertensive agents.
“Importantly,” Tomaszewski said, “we now have a biochemical test to detect the presence of antihypertensive medications that can be used to define whether or not the patient has been taking the drugs they have been prescribed.”
A major obstacle in the management of nonadherence to antihypertensive treatment has been the lack of direct, sufficiently sensitive, and reproducible methods of its detection in clinical practice.
The study included 676 patients from the UK whose urine samples were screened with the assay for suspected nonadherence between 2011 and 2014 and an additional cohort of 672 patients from the Czech Republic whose blood samples were screened between 2010 and 2016.
The rates of nonadherence to antihypertensive treatment were 41.6% in the UK population and 31.5% in the Czech population.
Nonadherence was inversely related to age and male sex. For every 10-year increase in age, in the UK there was a 33% reduction in the odds of nonadherence, and in the Czech Republic, the reduction was 31% (P<0.001 for both).
And women were less adherent to antihypertensive treatment than were men in both populations. In the UK, the odds of nonadherence were 65% higher (P=0.005) in women than in men. In Czech patients, the odds of nonadherence were 55% higher (P=0.014) in women than in men.
Patients on multiple antihypertensive agents had the highest nonadherence rates. In the UK, 79.3% of patients prescribed six or more blood-pressure–lowering drugs were nonadherent to antihypertensive treatment, and a similar finding was seen in Czech patients.
On average, for every extra blood-pressure–lowering drug that was prescribed, there was an 85% increase in the odds of nonadherence in the UK population and a 77% increase in the Czech group (P<0.001 for both).
Diuretics were associated with the highest odds of biochemical nonadherence among five classes of antihypertensive medications in both UK and Czech populations. After adjustment for age, sex, and the number of prescribed medications, the odds of nonadherence to diuretics were 76% increased (P<0.001) among the UK population and 63% increased (P=0.005) in the Czech population.
“We suspect that the side effects of the diuretics are probably most likely to account for this lower rate of adherence,” Tomaszewski said.
Sometimes, he said, he sees referrals from both primary and secondary care of patients who are taking eight or nine antihypertensive medications. “I can understand that when someone is prescribed eight or nine antihypertensives on top of other pills, it is just impossible logistically to deal with administrations of those medications. It is off-putting, and those patients eventually become so fed up they stop taking the medications.”
On the basis of these findings, the researchers suggest a model that includes age, sex, diuretics, and the number of prescribed antihypertensives for predicting nonadherence where biochemical testing is not available.
“This model is not ready for introduction into clinical practice,” said Tomaszewski. “But these four factors should be the foundation of any future-predicting algorithm that may be developed because we know that those factors are strong determinants. More work is needed to find additional predictors for such an algorithm.”
In an accompanying editorial[2], Dr David J Hyman (Baylor College of Medicine, Houston, TX) writes that the generalizability of the model is severely limited by the sample from which it is derived.
Hyman suggests that the investigators did not report data on other important variables for patients treated with multiple drugs that could make controlling their hypertension more difficult, such as poor renal function.
He also notes limitations to biochemical testing in this setting and predicts that, as patients become more familiar with testing and “it loses its element of surprise, patients with complex agendas will quickly learn to take pills before a visit, further reducing the value of the testing.”
Hyman concludes that more research is needed to treat patients with uncontrolled blood pressure despite being on multiple antihypertensive medications and how to address medication nonadherence.
Tomaszewski reports no relevant financial relationships; disclosures for the coauthors are listed in the paper. and Hyman reports no relevant financial relationships.
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