Assessment of a non-physician screening program for hypertension and cardiovascular risk in community pharmacies.

BACKGROUND AND AIMS: The strategic role of prevention in hypertension setting is well known but, with the only exception of annually events promoted by international scientific societies, no other screening campaigns are available. Aim of this study was to assess the feasibility of a non-physician pharmacy-based screening program and to describe the cardiovascular risk and the BP status of participating subjects. METHODS AND RESULTS: 2731 costumers participated to the screening program, answering to a questionnaire about personal cardiovascular risk and measuring their BP with an Omron HEM 1040-E. Since no threshold for hypertension diagnosis is currently available for community pharmacies BP measurements, we assessed high BP prevalence according to 3 different cut-offs (≥140/90, ≥135/85 and ≥ 130/80 mmHg) and compared normotensives and hypertensives on major cardiovascular risk factors. According to the proposed cut-offs, prevalence of hypertension was respectively of 31%, 45% and 59.5%, and it increased among younger subjects (31-65 y) when the lowest cut-offs were applied. High BP was found in a large percentage of subjects self-declared on-/not on-treatment (uncontrolled hypertensives) or normotensives (presumptive hypertensives) and among those not aware of their own BP values (presumptive hypertensives). Prevalence of CV risk factors was higher in hypertensives than in normotensives. CONCLUSIONS: Our findings demonstrated that a community pharmacy-based screening is feasible and attracts the interests of many subjects, improving awareness on their BP status. The screening was also showed to be useful in order to detect potentially uncontrolled and/or suspected new hypertensives, especially among young adults, to refer to general practitioners for confirmatory diagnosis or further evaluation.

Comparison of Automated Office Blood Pressure With Office and Out-Off-Office Measurement Techniques.

Automated office blood pressure (AOBP) has emerged as a valuable tool to assess patient's BP status, but the lack of strong evidence to establish a threshold value for hypertension diagnosis limits its use in clinical practice. We aimed at synthesizing the published literature through a meta-analysis of studies comparing AOBP with other BP measurement techniques and at analyzing the differences between AOBP and physician's office BP, nonphysician's office BP, daytime ambulatory BP monitoring, and home BP monitoring. We searched PubMed database for articles published up to April 2018; eligible studies compared AOBP with office and out-of-office measurement techniques and reported the BP differences or BP values obtained. Twenty-six studies, for a total of 7116 patients, were included in the analysis. AOBP values were lower than physician (systolic BP, -10.48 mm Hg; 95% CI, -13.15 to -7.81/diastolic BP, -4.44 mm Hg; 95% CI, -6.07 to -2.80) and nonphysician office ones (systolic BP, -6.89 mm Hg; 95% CI, -8.75 to -5.04/diastolic BP -3.82 mm Hg; 95% CI, -4.86 to -2.78). No significant differences were found between AOBP and daytime ambulatory BP monitoring (systolic BP, -1.85; 95% CI, -4.50 to 0.79/diastolic BP, 0.12; 95% CI, -1.42 to 1.66) and home BP monitoring (systolic BP, -2.65; 95% CI, -8.42 to 3.12/diastolic BP, -1.67; 95% CI, -4.20 to 0.87). AOBP readings did not differ significantly from out-of-office blood pressure, still remaining an office technique; it may improve hypertension diagnosis by overcoming some of office BP limitations, including the white coat effect.

A simple UHPLC-PDA method with a fast dilute-and-shot sample preparation for the quantification of canrenone and its prodrug spironolactone in human urine samples.

INTRODUCTION: Nowadays, the treatment of hypertension represents an important issue, particularly in developed countries. While in most cases the standard therapeutic approaches, consisting in the administration of 1 to 3 drugs, are adequate to reach adequate blood pressure levels, in some cases more drugs are needed: this condition is called "resistant hypertension". In this context, the administration of a diuretic, such as spironolactone or canrenoate salts, represents a standard practice. Since a reliable discrimination of real cases of resistant hypertension from cases of poor therapeutic adherence is currently difficult to obtain, the adoption of therapeutic drug monitoring has been suggested as a useful tool for this purpose. In this work, the authors developed and validated a simple, cheap and fast dilute-and-shot method with UHPLC-PDA analysis for the quantification of spironolactone and its metabolite canrenone in human urine samples. METHODS: Standards and quality controls were prepared in urine. Only 100 µL of sample were added with 80 µL of internal standard (6,7-dimethyl-2,3-di(2-pyridyl)quinoxaline) working solution and 820 µL of phosphate buffer 10 mM pH 3.2 (phase A):acetonitrile (phase B) 90:10 v:v solution. Chromatographic separation was performed on an Acquity® UPLC HSS T3 1.8 µm 2.1 × 150 mm column, with a binary gradient for 11 min at 40 °C. RESULTS: Accuracy, intra-day and inter-day precision, selectivity and sensitivity fitted FDA guidelines for all analytes (LLOQ and LOD were 156.25 ng/mL and 78.12 ng/mL, respectively, for both analytes) and recovery resulted high and reproducible. Method performances were tested on urine samples from hypertensive patients with good results. DISCUSSION: This simple analytical method could represent a useful tool for the management of antihypertensive therapy.

Therapeutic drug monitoring-guided definition of adherence profiles in resistant hypertension and identification of predictors of poor adherence.

AIMS: Arterial hypertension is an important cardiovascular risk factor. A substantial proportion of patients show resistance to antihypertensive treatment but poor adherence to medication regimens is also a significant cause of treatment failure. In this context, therapeutic drug monitoring (TDM) could be useful. The objective of this study was to assess adherence to treatment in patients with resistant hypertension by TDM and to identify parameters that predict nonadherence. METHODS: Liquid chromatography tandem mass spectrometry was used to quantify a wide panel of antihypertensive drugs in human plasma to assess treatment compliance. Associations between TDM-determined adherence profiles, self-reported adherence and other patient-related clinical, anthropometric or demographic features were evaluated as potentially useful pre-TDM predictors of poor adherence. RESULTS: TDM was performed on 50 patients with suspected resistant hypertension: 24% of patients partially complied to treatment and 18% were nonadherent. No concordance was observed with questionnaire results, while nonadherence was associated with high diastolic blood pressure, high heart rate, previous onset of stroke and previous use of invasive treatments, including renal denervation or baroreceptor stimulation. CONCLUSIONS: This evidence highlights the high prevalence of poor adherence in patients with resistant hypertension and the need for caution in using invasive approaches. These preliminary data require validation in a larger cohort, to confirm the need for TDM in routine clinical practice.

Effectiveness of Renal Denervation in Resistant Hypertension: A Meta-Analysis of 11 Controlled Studies.

INTRODUCTION: Early uncontrolled studies reported large blood pressure reductions in subjects with resistant hypertension treated with renal denervation, however these results were not confirmed in several of the latest publications. AIM: The aim of the current study was to evaluate the effectiveness of RDN in controlled studies comparing RDN to either a sham procedure or to medical therapy. METHOD: Only controlled studies were included in the analysis. Both the unadjusted and control-adjusted BP changes were calculated. RESULTS: We identified 11 publications of which only 3 were double-blinded RCTs with a sham control, while 8 were open label studies where the control group was treated with medical therapy. Only 2 studies assessed adherence to medical therapy with robust methodologies. Office BP reduction (- 18/8 mmHg) significantly overestimated ABPM change (- 9/- 5 mmHg), with high heterogeneity between the included studies. When the treatment effect was adjusted for the BP change in the control group, BP changes became non significant (ABPM: - 1.8 for systolic BP [95% CI - 4.5 to 0.9] and - 0.6 for diastolic BP [95% CI - 2.3 to 1.2]). These results were confirmed when only the sham-controlled studies were analysed. CONCLUSIONS: In spite of promising results in early reports, renal denervation fails to show superiority to a sham procedure or to medical therapy in recently published controlled studies. Lack of a sham control in most publications and heterogeneity in assessment of treatment adherence may account for part the variability reported in the studies. Renal denervation fails to show superiority to a sham procedure or to medical therapy in recently published controlled studies.

UHPLC-MS/MS method with sample dilution to test therapeutic adherence through quantification of ten antihypertensive drugs in urine samples.

Nowadays, hypertension represents an important health problem, particularly in developed countries. In some cases the standard therapeutic approaches are not able to reestablish the normal blood pressure values: this condition is called "resistant hypertension". However, a fraction of cases of resistant hypertension are actually due to poor adherence to the prescribed therapy. Therapeutic Drug Monitoring could represent a direct and useful tool to correctly identify non-compliant patients. Nevertheless, high throughput methods for the simultaneous monitoring of a wide panel of drugs in the same analysis are lacking and, furthermore, there is not a generally acknowledged "standard" matrix for this test (plasma or urine). In this work, we validated a UHPLC-MS/MS assay to quantify ten among the most used antihypertensive agents in urine samples, covering all the current classes: amlodipine, atenolol, clonidine, chlortalidone, doxazosin, hydrochlorothiazide, nifedipine, olmesartan, ramipril and telmisartan. Both standards and quality controls were prepared in urine matrix. Only 100µL of each sample were added with 40µL of internal standard and 860µL of water:acetonitrile 90:10, acidified with 0.05% formic acid. Chromatographic separation was performed on an Acquity® UPLC HSS T3 1.8µm 2.1×150mm column, with a gradient of water and acetonitrile, both added with 0.05% formic acid. Accuracy, intra-day and inter-day precision fitted FDA guidelines for all analytes, while matrix effects resulted reproducible among different urine lots. Method performances were tested on urine samples from hypertensive patients with good results. This simple analytical method could represent a useful tool for the management of antihypertensive therapy.

Evaluation of a short home blood pressure measurement in an outpatient population of hypertensives.

Current guidelines suggest the use of home blood pressure monitoring (HBPM) as a method complementary to ambulatory blood pressure monitoring (ABPM) for the identification of arterial hypertension. A cross-sectional study was conducted to evaluate the accuracy of a short HBPM schedule compared with ABPM, and to evaluate to what extent HBPM can replace ABPM. A total of 310 patients who performed ABPM in our hypertension clinic were enrolled between November 2011 and June 2015. They performed a 4-day HBPM schedule, with two readings in the morning and two readings at night. Results showed a moderate correlation between HBPM and ABPM (r = 0.59 for systolic blood pressure (SBP) and r = 0.72 for diastolic blood pressure (DBP)) and moderate diagnostic agreement (area under curve: 0.791 for SBP and 0.857 for DBP). No significant difference was found between first-day average and those of days 2-4. Diagnostic agreement between the two techniques was moderate, supporting the notion that HBPM cannot replace ABPM in the general population. However, we identified two HBPM thresholds, 123/75 and 144/87 mm Hg, through which subjects who may not require further ABPM can be identified.

UHPLC-MS/MS method with protein precipitation extraction for the simultaneous quantification of ten antihypertensive drugs in human plasma from resistant hypertensive patients.

Today the management of resistant hypertension is a critical health problem: the main difficulty on this field is the discrimination of cases of poor therapeutic adherence from cases of real resistance. This gives rise to the need of high throughput and reliable quantification methods for the Therapeutic Drug Monitoring (TDM) of antihypertensive drugs. The aim of this work was the development and validation of a UHPLC-Tandem mass spectrometry assay for this application and its use in plasma from patients with resistant hypertension. The novelty of this method resides in the ability to simultaneously quantify a wide panel of antihypertensive drugs: amlodipine, atenolol, clonidine, chlortalidone, doxazosin, hydrochlorothiazide, nifedipine, olmesartan, ramipril and telmisartan. Moreover, this method stands out for its simplicity and cheapness, resulting feasible for clinical routine. Both standards and quality controls were prepared in human plasma. After the addition of internal standard, each sample underwent protein precipitation with acetonitrile and was then dried. Extracts were resuspended in water:acetonitrile 90:10 (0.05% formic acid) and then injected into the chromatographic system. Chromatographic separation was performed on an Acquity(®) UPLC HSS T3 1.8µm 2.1×150mm column, with a gradient of water and acetonitrile, both added with 0.05% formic acid. Accuracy, intra-day and inter-day precision fitted FDA guidelines for all analytes, while matrix effects and recoveries resulted stable between samples for each analyte. Finally, we tested this method by monitoring plasma concentrations in 22 hypertensive patients with good results. This simple analytical method could represent a useful tool for the management of antihypertensive therapy.

Adherence to antihypertensive therapy and therapeutic dosage of antihypertensive drugs.

Adherence to antihypertensive therapy is critical to achieving adequate blood pressure control. About half of hypertensive patients do not take their drugs as directed and the physicians often underestimate this issue. Non-adherence has important public health economic implications (numbers of visits, diagnostic procedures, prescribed drugs) and, moreover, it results in increased morbidity and mortality rates. Poor adherence can have several patients and therapy related causes. Currently, multiple different direct and indirect methods to measure therapeutic adherence are available, but, in clinical practice, there is no cost-effective and simple one. Therapeutic drug monitoring (TDM), characterized by drug (or metabolites) concentration measurement in body fluids (blood or urine), is a cost-effective direct method to assess therapeutic adherence. Despite some limitations, TDM may decrease health costs, by reducing the number of visits and by identifying those patients who would undergo unnecessary invasive procedures. Moreover, TDM can be a new alternative method to identify patients with true resistant hypertension, improving the achievement of blood pressure control In this minor revision, we would assess poor therapeutic adherence in hypertensive population, analyzing the different direct and direct available methods, with emphasis on TDM.