Long-Term Effects of Renal Artery Denervation

Background and Objectives: Renal artery denervation (RDN) procedure is a broadly discussed method in the treatment of resistant hypertension. Many studies report short-term (3–12 months) results for blood pressure and arterial stiffness. The primary endpoints were changes in 24 h mean systolic blood pressure (BP) and office systolic BP 48 months after RDN. The secondary endpoints were changes in aortic pulse wave velocity and impact of polypharmacy on these variables. Materials and Methods: Renal artery denervation was performed in 73 patients treated for resistant hypertension; 49 patients remained in final analysis. Patient examination was carried out before the procedure, and subsequently at 3, 6, 12, 24, and 48 months later. Patients’ antihypertensive and overall medication regimens were carefully analysed. Results: Mean 24 h arterial blood pressure lowered and was sustained at lower levels for up to 48 months; median (interequartile range—IQR) from 158(23.5)/100(14.2) to 140(26.5)/86(16.2) mmHg. Mean reduction in 24 h ambulatory systolic BP was −11 ± 25 mmHg (95% CI, −20 to −2; p < 0.001), while office systolic BP reduced by −7 ± 23 mmHg (95%CI, −24 to −1; p < 0.02). A significant reduction in median aortic pulse wave velocity 12 months after the procedure (drop from baseline 11.2 [3.15] m/s (95%CI 6.1 to 16.2) to 9.8 [2.1] m/s (95%CI 6.1 to 13.7; p = 0.002)). After 48 months, there was no worsening compared to the baseline level of 10.3 [4.0] m/s (95% CI 6.9 to 17.8) (p > 0.05). The total mean number of antihypertensive drugs remained unchanged: 5.97(±1.1) vs. 5.24 (±1.45). A higher number of pills after 48 months was associated with higher aortic pulse wave velocity (1–5 pill group: 8.1 ± 1.6 m/s; 6–10 pill group: 10.9 ± 1.8 m/s; >11 pill group: 15.1 ± 2.6 m/s) (p = 0.003). Conclusions: Antihypertensive effect after renal denervation lasts up to 48 months with no worsening of arterial stiffness compared to baseline. In our study, polypharmacy was associated with increased arterial stiffness 48 months after the procedure.

Abstract 16361: Effects of Low-dose Triple Combination Therapy on Time at Target Blood Pressure - Results From the TRIUMPH Randomized Controlled Trial

Introduction: Cumulative exposure to hypertension is an adverse prognostic marker. However longitudinal assessments of blood pressure (BP), i.e. TIme at TaRgEt (TITRE), are not routinely assessed in practice. Specifically, the effect of low-dose combination anti-hypertensive therapy on TITRE has not been studied. Hypothesis: Low-dose triple combination antihypertensive medication achieves greater TITRE compared to usual care. Methods: TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomized controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients from urban hospital clinics in Sri Lanka were randomised to either once-daily low-dose triple combination polypill (20mg of telmisartan, 2.5mg of amlodipine, and 12.5mg of chlorthalidone) or standard care. This analysis compared TITRE in the intervention and usual care groups over 6 months follow-up, with TITRE defined as percentage of time at target BP. Target BP was defined as <140/90mmHg or <130/80mmHg in patients with diabetes or chronic kidney disease. Results: The trial comprised 700 patients (mean [±SD] age: 56±11 years, 58% women). Patients in the triple pill group (n=349) achieved a higher TITRE compared to those in the standard care group (n=351) at 6 months (64±32% vs 43±34%, risk difference -21%, 95%CI -26% to -6%, p<0.001). Almost twice as many patients in the triple pill group spent the majority of follow-up time at target (TITRE >50%: 64% vs 37%, p<0.001). The effect of the triple pill was seen early, with the majority achieving TITRE >50% by 12 weeks. Those on the triple pill achieved a consistently higher TITRE at all follow-up periods compared to usual care (0-6 weeks: 36±31% vs 21±28%; 6-12 weeks: 74±39% vs 46±43%; 12-24 weeks: 77±37% vs 53±44%, all p<0.001). When predictors of TITRE were examined, only triple pill therapy was predictive of TITRE >75% (odds ratio [OR] 3.41, 95%CI 2.30-5.04, p<0.001). Conclusion: Among patients with mild-moderate hypertension, treatment with a low-dose triple combination pill significantly increased time at target compared to usual care. This study also introduces TITRE as a novel outcome assessing longitudinal BP control in trials.

Effects of Miracle Fruit Supplement on Hedonic Responses to Different Types of Sour Food in Asian Americans with Diabetes or Prediabetes

Objectives More than 100 million U.S. adults are living with diabetes or prediabetes. Sugar substitutes have long been counted on by people with diabetes or prediabetes. Miracle fruit has been considered as a healthy natural alternative sweetener that can meet diabetic patients’ needs due to its sweetness-enhancing effect and health benefit such as high antioxidant activities. The objective of this study was to examine if there is any significant difference in pre-post hedonic response changes to different sour food products between the miracle fruit and the placebo treatment in people with diabetes or prediabetes. Methods This study has a randomized, controlled, crossover design of two-treatment, two-day session trials with each session comprising pre and posttest. In session 1, 25 participants out of the 50 Asian Americans with diabetes or prediabetes (Women 60%, Mean ± SE = 54.7 ±1.3 years of age) were randomly assigned to miracle fruit pill group and the other 25 participants were assigned to placebo (sugar pill) group. In session 2, the assignment was switched. In each session, participants assessed their hedonic responses to green apple, goat cheese, lemonade, cucumber pickle, and plain fat-free yogurt before and after miracle fruit pill/placebo administration. Testing order of samples was randomized for each participant. The pre and post likings for overall, flavor, texture, and aftertaste were evaluated using a 9-point hedonic scale. Paired t-tests were used to examine the differences between the two groups. Results In posttests, all the hedonic responses improved regardless of the treatment. However, the miracle fruit group's pre-post difference values in all the hedonic attributes for all the food samples evaluated were significantly higher than the placebo group's values (P &lt; 0.001). The largest difference value (3.1 ± 0.19) was observed for the flavor liking of yogurt in the miracle fruit group and the smallest difference value (0.3 ± 0.13) for the overall and aftertaste liking of goat cheese in the placebo group. Conclusions This study suggests that miracle fruit can be used as an effective sweetness enhancer to improve hedonic responses to sour foods in people with diabetes or prediabetes. Funding Sources Professional Staff Congress-The City University of New York (PSC-CUNY) 50 Grant (#62,192–00-50).

1423Adherence to triple component antihypertensive regimen is higher in single-pill combination than two-pill regimen: data from a randomized controlled trial using medication event monitoring system

Background Simplicity of regimen is known to be an important determinant of medication adherence and using single-pill combination (SPC) in hypertension treatment resulted in better adherence and persistence than free-equivalent combination. However, this finding has been studied only in dual-component antihypertensive treatments and in observational studies using medication possession ratio as an index of adherence. Medication event monitoring system (MEMS) is considered to be the gold standard in estimating medication adherence. Purpose To investigate the superiority in adherence of triple-component SPC compared to equivalent two-pill regimen using MEMS Methods This is a multi-center open-label randomized controlled trial. Inclusion criteria were hypertensive patients whose clinic blood pressure is not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with combination antihypertensive regimen comprising two of three classes (angiotensin receptor blocker, calcium channel blocker and thiazide diuretics) for at least 4 weeks. Eligible patients were randomized either to single-pill (triple-component SPC, olmesartan/amlodipine/ hydrochlorothiazide 20/5/12.5 mg) or two-pill (dual-component SPC + one free pill, olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) groups and maintained for 12 weeks. Medications were dispensed in MEMS. Primary outcomes were the difference of percentage of dose taken (PDT) and percentage of days with prescribed dose taken correctly (PDTc) between single- and two-pill therapy, calculated from MEMS data. Results From 8 hospitals, 146 hypertensive patients were randomized into single- and two-pill groups. Final analysis was done in 65 and 66 patients in each group from which adherence index could be obtained. Baseline clinical characteristics of the two groups were not different. The single-pill group had significantly higher PDT and PDTc compared to the two-pill group. (median (25–75 percentile) (%), PDT 95.1 (87.9 - 100.0) vs 91.2 (79.8 - 96.5); PDTc 93.1 (79.8 - 96.5) vs 91.3 (70.7 - 96.4), p = both 0.04, by Wilcoxon rank sum test) Percent dose taken Conclusion Single-pill combination of triple-component antihypertensive regimen showed superior adherence compared to equivalent two-pill therapy. Reducing pill burden by using SPC is a relevant strategy to enhance the adherence to multi-drug antihypertensive therapy. Acknowledgement/Funding Daiichi-Sankyo

Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and Its Mediators

Objective Transdermal, but not oral, estrogen replacement improves bone mineral density (BMD) in athletes with oligoamenorrhea (OA). Our objective was to determine mechanisms that may explain the impact of route of estrogen administration on bone outcomes. Methods Seventy-three participants with OA between 14 and 25 years old received (i) a 17β-estradiol transdermal patch continuously with cyclic oral micronized progesterone (PATCH), (ii) a combined ethinyl estradiol and desogestrel pill (PILL), or (iii) no estrogen/progesterone (NONE) for 12 months. We evaluated morning fasting levels of a marker of bone formation [N-terminal propeptide of type 1 procollagen (P1NP)], a marker of bone resorption (N-telopeptide), IGF-1, insulinlike growth factor binding protein 3, total testosterone, estradiol, SHBG, sclerostin, preadipocyte factor-1 (Pref-1), brain-derived neurotrophic factor (BDNF), calcium, 25(OH) vitamin D, and PTH levels at baseline and 12 months. Results Groups did not differ for age, weight, exercise activity, or markers of bone formation at baseline. Over 12 months, P1NP decreased the most in the PILL group (P = 0.03) associated with a decrease in IGF-1 levels (r = 0.37; P = 0.003). Sclerostin, Pref-1, and BDNF decreased in the PATCH group over 12 months. PATCH had the greatest increases in estradiol (P ≤ 0.0001), and estradiol increases were associated with increases in bone density. Conclusion Transdermal 17β-estradiol given over 12 months does not cause the decrease in IGF-1 observed with oral ethinyl estradiol. It also leads to decreases in sclerostin, Pref-1, and BDNF, which may mediate the beneficial effects of estrogen.

Comparison of a Paper Pill with a Conventional Oral Contraceptive Tablet

A multicentre clinical trial comparing a novel formulation (the Paper Pill) of a combined oral contraceptive containing 30 μg ethinyloestradiol and 150 μg levonorgestrel with a conventional tablet formulation (Microgynon 30) has been carried out in 336 women over 6 cycles. There were no pill failures in women taking either preparation with one exception in the Microgynon 30 group which was due to poor patient compliance. Cycle control judged by cycle length, duration and amount of withdrawal bleeding and the incidence of intermenstrual bleeding was good in both groups. The number of adverse effects was slightly less in the Paper Pill group and fewer withdrawals for medical reasons were noted than in the Microgynon 30 group. A questionnaire showed that the Paper Pill was accepted well by the majority of women in the trial.