Branislav Štrauch

Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence ( P <0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications ( P ≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure–lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (-8.6 [95% cofidence interval: -11.8, -5.3] mm Hg; P<0.001 in renal denervation versus -8.1 [95% cofidence interval: -12.7, -3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (-12.4 [95% cofidence interval: -17.0, -7.8] mm Hg; P<0.001 in renal denervation versus -14.3 [95% cofidence interval: -19.7, -8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy.

We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry–based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0–0.67) to 1 (0.67–1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline ( P =0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic—their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively ( P &lt;0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography–tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.

BACKGROUND: The aim of our study was to assess the prevalence of pseudo-resistance caused by noncompliance with treatment among patients with severe resistant hypertension and to analyze the contributing factors. METHOD: Three hundred and thirty-nine patients (195 men) with resistant essential hypertension were studied. The first group consisted of 176 patients admitted for hospitalization for exclusion of a secondary cause to our hypertension centre (103 men); the second one consisted of 163 out-patients (92 men) investigated for the first time in an out-patient hypertension clinic. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by means of liquid chromatography-mass spectrometry was performed in all patients. RESULTS: Our main finding is a surprisingly low compliance with drug treatment in out-patients with resistant hypertension (23% partially noncompliant and 24% totally noncompliant - in total, 47% prevalence of noncompliance). Eighty-one percent of hospitalized patients were positive, in 10% the results were partially positive and in 9% of the patients, the drugs were all negative. The compliance among hospitalized patients was probably better due to lower numbers of prescribed drugs and expected thorough investigation. More frequently, noncompliance was found in nonworking (potential purpose-built behaviour), younger and less well educated patients. The most frequent noncompliance was to doxazosine, spironolactone and hydrochlorothiazide. We have observed a surprisingly low compliance with treatment among out-patients with severe hypertension. CONCLUSION: We conclude that the evaluation of antihypertensive drugs concentrations is a useful and precise method for assessment of noncompliance in patients with resistant hypertension. This evaluation is useful before starting the diagnostic work-up of secondary forms of hypertension and before assignment patients into protocols with new therapy modalities such as renal denervation.