Dried Blood Spot to Screen for Antihypertensive Medications and to Asses Treatment Adherence.

Despite the multiplicity of national and international initiatives encouraging the detection and management of subjects with an elevated blood pressure (BP), hypertension awareness, treatment, and control remain insufficient worldwide. Indeed, among patients receiving antihypertensive medications, target BP is achieved at best in half of them in the United States, and results are unfortunately much lower in low/middle-income countries. Besides the common problems of drug availability and therapeutic inertia, which result in an inadequate management of many hypertensive patients, poor adherence to prescribed medications has been identified as a frequent cause of uncontrolled hypertension resulting in poor cardiovascular outcomes. Therefore, most recent guidelines have put a strong emphasis on detecting and supporting drug adherence to improve BP control and have provided some clues on how to consider modifiable determinants of adherence. Today, patients with a poor adherence remain largely unrecognized for several reasons. One of them, regularly notified by treating physicians, is the absence of a reliable, easy-to-use, and cheap tool enabling to detect patients who do not take their treatments as prescribed. In addition, as adherence is highly variable within the course of therapies, physicians should also be able to test it repeatedly at reasonable costs as a support for their therapeutic interventions. In this issue of Hypertension, Peeters et al present data on a new method developed to monitor drug adherence easily using dried blood spot (DBS) sampling and analysis of 8 antihypertensive drugs and 4 active metabolites using ultra-high performance liquid chromatography–tandem mass spectrometry. They conducted this single center-study in 135 hypertensive patients in whom drug concentrations were measured simultaneously using the DBS approach and on plasma samples. They also evaluated pharmacokinetic parameters and the impact of various clinical parameters responsible for the intraand interpatient variability of plasma drug levels. To that purpose, a broad range of trough levels was sampled up to around 40 hours after drug intake. Results show that DBS could detect drug levels of the chosen compounds within a median time of 25 hours after the last reported drug intake. The lower levels of detection and quantification were higher in DBS compared with plasma; hence DBS is less sensitive for measuring trough levels of antihypertensive drugs. However, in several cases, DBS concentrations were actually higher than those measured in plasma at trough, probably because DBS measured drug concentrations in the whole blood including cells. When DBS results were negative, plasma values were generally negative. Data show that the determination of hydrocholorothiazide remains more problematic than that of blockers of the renin-angiotensin system or calcium channel blockers. Few false negative values were observed with DBS, which could be explained by the time between intake and sampling. The variability of trough drug levels was very high in this patient group. The main determinants of this variability were age, weight, and sex and as expected, the time between intake and sampling and the dose of the drugs. Authors conclude that DBS may be a suitable method to detect poor adherence in hypertension although the method still needs to be ameliorated and validated for larger groups of patients with controlled or uncontrolled hypertension. In this respect, a large clinical trial is ongoing in patients with resistant hypertension, in which this new method will be used to monitor drug adherence (trialregister.nl; NTR6914). The ability to screen for the presence of antihypertensive drug using the DBS sampling method can be of great clinical value because of its simplicity and its possible application not only in hypertension centers but also in physicians’ offices. In fact, the DBS idea is not entirely new. Yvar Bang published the concept of measuring substances on a dried blood matrix in 1913, and R. Guthrie used this approach successfully later on to screen for phenylketonuria. Since then, the method has improved considerably mainly through the development of analytical methods such as liquid chromatography and mass spectrometry. Today, >120 biomarkers and drugs are measurable using DBS sampling including some antihypertensive drugs. Though seemingly unsophisticated, the DBS methodology is nevertheless facing several analytical pitfalls that must be taken into account to ensure the adequacy of the results as reviewed by Zakaria et al. The establishment of reference intervals or decision limits appears to be essential for DBS analytes. For the screening of drug adherence, it might be sufficient to detect if the drug is present or absent of the blood sample as it is done today with urine samples. However, the method should not generate too many false negative results to avoid accusing inappropriately patients of nonadherence. The data presented by Peeters et al seem somehow reassuring in this respect. The quantitative interpretation of DBS-measured blood concentrations is much more difficult The opinions expressed in this article are not necessarily those of the American Heart Association. From the Hypertension Research Foundation, Saint-Légier, Switzerland. Correspondence to Michel Burnier, Hypertension Research Foundation, Derrey le Motty 8, 1806 St Légier, Switzerland. Email michel.burnier@ netplus.ch Dried Blood Spot to Screen for Antihypertensive Medications and to Asses Treatment Adherence