Abstract 15986: Plasma Microrna Profiling Reveals Potential Biomarkers of Thiazide Response

Introduction: Thiazide diuretics (TZDs) are the second most frequently prescribed class of antihypertensives. But <50% patients achieve goal blood pressure (BP) on TZD monotherapy, mostly because therapy is chosen overlooking the heterogeneity in patient responses. Circulating microRNAs (miRNAs) remain attractive as non-invasive biomarkers to predict drug response and tailor therapy for optimal outcomes. Hypothesis: Plasma miRNAs may play a role in TZD response; we aim to identify those associated with hydrochlorothiazide (HCTZ) response. Methods: We profiled 754 miRNAs in baseline (untreated) plasma samples of 36 uncomplicated hypertensive adults (18 Responders (R) and 18 Non-responders (NR) based on their diastolic BP (DBP) response to HCTZ therapy) from the Pharmacogenomic Evaluation of Antihypertensive Responses clinical trial, using the real-time qPCR based TaqMan OpenArray Human microRNA panel. We filtered out miRNAs with low amplification scores and Cq>38 and samples with low miRNA expression. Combination of miR-223 and miR-19b (identified as most stably expressed miRNAs by NormFinder Software) was used to normalize expression across samples. We used MannWhitney U test to identify microRNAs differentially expressed between R and NR; linear and logistic regressions for associations of miRNA expression with BP response. FDA corrected p<0.05 was used as significance threshold, unadjusted p<0.05 as suggestive threshold. Results: Mean systolic BP (SBP)/DBP change in R was 14/10 mmHg and in NR 0/1 mmHg. We found 77 miRNAs to be consistently expressed across samples, of which 11 were upregulated and 14 downregulated with >2-fold difference between R and NR. Though no miRNAs reached FDR p<0.05, miR-376a (fold change(fc)= 10.1, p= 0.035) and miR-17 (fc= -0.45, p= 0.017) were differentially expressed between R and NR and their expression associated with DBP and SBP change, along with miR-10b, miR-24, miR-134 associated with SBP change at p<0.05. Conclusions: In this first ever genome-wide miRNA study of antihypertensive drug response, we discovered circulating miRNAs associated with BP response to HCTZ. Future studies are planned to validate these findings in a larger cohort, across different race group and across different TZD.

CORRECTION OF RESISTANT ARTERIAL HYPERTENSION IN PATIENTS WITH CHRONICKIDNEYDISEASE STAGE I–III

Aim. The aim was to investigate the use of the I1–imidazoline receptor agonist moxonidine as an ‘add–on’ agent and determine its effect on heart rate variability in patients with CKD st. I–III and resistant hypertension. Methods. We investigated the safety and efficacy of moxonidine (200–600 mg) in a group of 35patients with CKD st. I–III whose had prior treatment with three or more antihypertensive medications, although without adequate control [systolic blood pressure (SBP) 145–165 mm Hg and/or diastolic BP (DBP) 95–100 mm Hg]. BP was measured according to internationally accepted guidelines before and after 3 month of treatment with moxonidine used as an ‘add–on’ agent in the patients with CKD st. I–III and resistant hypertension. Age ofpatients was 53±5,8 years. Glomerular filtration rate (GFR) before treatment was 68,7±23,0 mL/min/1,73m 2. Before and 3 months after treatment, we determined improvement in the time–frequency analysis of heart rate variability. Results. Following treatment with moxonidine, the SBP significant fell from 153.6±8.1 to 130.7±4.6 mmHg (P< 0.001). The DBP also showed a significant reduction from 96.7±2,4 to 80.9±2,6 mmHg (P< 0.001). Reduction of SBP pressure was 22.9±7.9 mm Hg and reduction of DBP was 15.9±3.1 mm Hg. 29patients (83%) achieved the goal blood pressure – 130/80 mm Hg and less. 5 patients (14%) were not achieve goal blood pressure, but blood pressure lowered <140/90 mm Hg. In 1 patient (3%) blood pressure decreased from 160/100 mm Hg to 145/90 mm Hg. The majority of patients (28 – 80%)

The relation of physicians to the goal blood pressure achievement and to the recommendations of arterial hypertension management. The problem of physicians’ inertia

Objective. To assess the attitude of primary care physicians in Russia to antihypertensive therapy administration and their readiness to achieve goal blood pressure, as well as causes of physicians’ inertia. Design and methods. The survey was performed in St Petersburg, Leningrad region (North-West region) and Irkutsk. The questionnaire was filled by 790 primary doctors (368 from St Petersburg, 57 in Leningrad region and 365 in Irkutsk). Results. More than half of Russian physicians were found to be predisposed to clinical inertia and the structure of its reasons is generally the same as in USA and Western Europe. The most frequent causes are contradictions between the good knowledge of the guidelines and subjective barriers to follow them in practice, especially in the elderly patients, overestimation of treatment success. Economical reasons are also relevant while lack of knowledge is less important.

Farmaci antipertensivi a confronto: costi e benefici per il paziente e la collettività

Pharmacoeconomic analysis of antihypertensive treatment should be performed following a correct methodological evaluation and considering with accuracy both costs and benefits of different therapeutic options. Costs evaluation is frequently performed simply examining the retail price of drugs which represents only a part (usually no more than 50%) of cumulative costs of therapy. Controlled clinical trials are the main source of information about benefits of therapy, but probably, in many cases, they underestimate the benefits of treatment and are unable to differentiate the effects of different drugs because of a too short follow-up. Benefits should be calculated not only in terms of saved lives or prevented events, but also in terms of prevention-regression of target organ damage and of quality of life of patients. If analysis are performed correctly, more recent drugs, like ATII antagonists, even if they have a higher retail price, become highly costeffective thanks to their protective activity against events, and to unbeatable levels of compliance and persistence which are associated with treatment with these drugs. Comparison between old (cheaper) and newer (more expensive) drugs, and recommendations to start therapy with the cheaper drugs, are a nonsense since to achieve goal blood pressure combinations of more drugs are always necessary. Treatment of hypertension, if extended to all patients and performed aggressively, must be considered not only a life-saving, but also a money-saving tool.