Under Pressure: Does Directly Observing Medication Administration Lower Blood Pressure?

Author(s)
Meagan A. Brown, PharmD, BCACP
Raven Jackson, PharmD

Reviewed By
Shaneka Baylor, Pharm.D., BCGP, BCACP
Vasudha Gupta, PharmD, BCACP, CDE

Citation
Ruzicka M, Leenen FHH, Ramsay T, et al. Use of directly observed therapy to assess treatment adherence in patients with apparent treatment-resistant hypertension. JAMA Intern Med. 2019; 179: 1433-4.

The Problem

Treatment-resistant hypertension, the need for 4 or more medications to achieve goal blood pressure (BP), occurs in nearly 1 in 5 patients.¹ But is it truly treatment-resistant? Nonadherence is often regarded as the primary cause in many patients.  But how can we distinguish between other causes of hypertension that should prompt additional diagnostic testing or treatment intensification? A recent study suggests there is a simple solution: watch them take their pills.

 

What’s Known

The term apparent treatment-resistant hypertension (aTRH) has been used to describe patients who remain uncontrolled despite the use of 3 medications (systolic >130 and/or diastolic >80 mmHg) or who must use 4 or more medications to get to goal. In the United States, the number of patients with aTRH was estimated to be 9.2 million in 2008 and, a decade later, had increased to 10.3 million people.¹  While aTRH is frequently attributed to medication nonadherence, it’s often difficult to assess.  There are no definitive ways to determine when treatment nonadherence is the culprit.  Many clinicians use pharmacy refill data, proportion-of-days-covered (PDC), and pill counts. Directly observed therapy (DOT) has been used in other disease states to measure treatment response or ensure that medications are taken.²

 

What’s New

In a small observational study, Canadian investigators used DOT to determine if treatment nonadherence was the likely cause of aTRH.³ The study was a prospective, cohort study where researchers enrolled patients with aTRH to undergo DOT with BP monitoring in clinic until the medications reached peak response. 24-hour ambulatory blood pressure monitoring (ABPM) was done immediately after peak response was met and repeated 1-month later. All patients were questioned about medication adherence and the clinic nurse performed a pill count and reviewed refill records for the prior 6 months.  Only those patients who claimed a high degree of adherence and with concordant pill counts and refill records were enrolled in the study.  The primary outcome was the proportion of patients who met the daytime mean systolic blood pressure (SBP) goal of less than 135 mm Hg on 24-hour ABPM after DOT and the secondary outcome was the proportion meeting this threshold one month later. A total of 60 patients enrolled in the study and 48 patients completed the initial 24 hour BP monitoring phase. Most patients were men (66.7%), middle-aged (mean age = 62 years), and overweight (mean BMI = 32). Most patients (90%) had prescription insurance coverage through a government-funded plan and had been prescribed an average of four BP-lowering medications. Common comorbidities among the enrolled patients included coronary artery disease, stroke, diabetes, and elevated daytime ABPM. After DOT, 14 of 48 patients (29%) achieved the daytime mean systolic BP goal (<135 mmHg) and 14 of 46 patients (30%) met the daytime mean systolic BP goal at one month. The findings suggest that nonadherence is high even among those who said they were adherent when questioned and whose pharmacy records suggest they were receiving medication refills at appropriate intervals.

 

 

Our Critical Appraisal

The study team, understanding the inadequacy of using direct questioning, pill counts, and refill data as a method of assessing adherence, opted to employ DOT. There has been much debate regarding the efficacy of DOT as it relates to long term behavior change as it takes the responsibility away from the patient. There are also substantial costs and logistical considerations when implementing DOT. Systolic BP remained 135 mmHg or greater in 71% of patients 24 hours after DOT, suggesting that many patients had hypertension due a secondary cause that require further investigation. However, most patients who had markedly improved BP levels after DOT had sustained BP control after 1 month. The BP inclusion criteria, daytime mean systolic BP of 135 mm Hg or higher, aligns with the 2018 American Heart Association statement for the treatment of hypertension in adults.

 

There were more men represented in this study and race was not mentioned which is not uncommon — women and minorities are often underrepresented in clinical trials. This makes extrapolation of these findings to populations often seen in ambulatory clinics in the U.S. problematic. The majority of people who experience aTRH in the US are non-Hispanic black patients and the causes might be different.³

 

Lastly, in regards to the study design, the implementation of a prospective observational cohort model seemed appropriate given the nature of the research. It is unclear what the “standard questioning” used by the clinic nurse involved. Depending on the length of the questionnaire, type of questions asked (i.e. open- or close-ended), patient’s literacy level, and a host of other factors, the standard questioning may or may not have obtained all necessary information from the patient. Understanding the why behind nonadherence, which is not fleshed out in this research letter, can be crucial in assisting patients with appropriate self-care behavior development and addressing access issues.

 

The Bottom Line

Pharmacists are in the best position to educate patients regarding the proper administration and use of medications and to help patients get to their blood pressure goal. Assessing medication adherence is one of the most important tasks pharmacists perform but the tools needed to get an accurate picture are lacking. These data provide some key insights into how to screen patients with aTRH. While the results of study might be due to the “Hawthorne” effect (aka the observer effect), DOT is a promising strategy. The provision of DOT face-to-face in clinic would be inconvenient for most patients and workflow changes would be needed in most settings. At this time there is no mechanism for payment – so economic sustainable of a DOT service must be considered.  However, telehealth technologies would permit remote observations, improving patient convenience and at a potentially lower cost. A virtual DOT clinic would be a unique service for pharmacists in community-based settings to offer and another opportunity to increase involvement in medication management.

 

The Key Points

• In patients with apparent treatment resistant hypertension, use a combination of methods to assess adherence.  Directly observed treatment is a promising strategy that can be used to differentiate between different causes of treatment resistance.
• Ask open-ended, conversational, intrinsically motivating questions to yield honest responses to assist in understanding the WHY behind nonadherence.
• Observing patients and monitoring their post-dose response to antihypertensive treatment is a great opportunity for pharmacists.

 

FINAL NOTE:  This program will be available for recertification credit through the American Pharmacists Association (APhA) Ambulatory Care Review and Recertification Program.  To learn more, visit https://www.pharmacist.com/ambulatory-care-review-and-recertification-activities.