scholarly journals Sex Differences in Spironolactone and the Active Metabolite Canrenone Concentrations and Adherence

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 137
Author(s):  
Laura E. J. Peeters ◽  
Leonardien K. Tjong ◽  
Wim J. R. Rietdijk ◽  
Teun van Gelder ◽  
Birgit C. P. Koch ◽  
...  
Keyword(s):  
Sex Differences ◽  
Resistant Hypertension ◽  
Active Metabolite ◽  
Drug Exposure ◽  
Antihypertensive Drugs ◽  
Controlled Trial ◽  
Linear Regression Models ◽  
Blood Concentrations ◽  
Males And Females ◽  
Post Hoc

We aim to investigate sex differences in blood concentrations of spironolactone and the active metabolite canrenone in resistant hypertension patients. Furthermore, sex differences in adherence for spironolactone and other antihypertensive drugs (AHDs) were studied. The patients in this post hoc study had all participated in a single-blind randomized controlled trial called RHYME-RCT (Dutch Trial Register, NL6736). Concentrations in blood of several AHDs were assessed in RHYME-RCT to investigate adherence to treatment. This allowed for a comparison of drug exposure to spironolactone and canrenone between males and females. In linear regression models, no statistically significant sex differences (N = 35) in spironolactone (B =−10.23, SE = 7.92, p = 0.206) or canrenone (B = 1.24, SE = 10.96, p = 0.911) concentrations after adjustment for dose and time between sampling and intake were found. Furthermore, no statistically significant differences in non-adherence to spironolactone were found between sexes (N = 54, male 15% vs. female 38%, p = 0.100), but non-adherence to spironolactone was associated with non-adherence to other AHDs (p ≤ 0.001). Spironolactone and canrenone concentrations were not different between males and females with resistant hypertension. Although not statistically significant, females were twice as likely to be non-adherent to spironolactone compared to males, and thereby also more likely to be non-adherent to other AHDs.

The Link Between Verbal Short-Term Memory and Anomia Treatment Gains

2019 ◽  
Vol 28 (3) ◽  
pp. 1039-1052
Author(s):  
Reva M. Zimmerman ◽  
JoAnn P. Silkes ◽  
Diane L. Kendall ◽  
Irene Minkina
Keyword(s):  
Short Term Memory ◽  
Controlled Trial ◽  
Treatment Success ◽  
Linear Regression Models ◽  
Language Performance ◽  
Short Term ◽  
Term Memory ◽  
Treatment Gains ◽  
Post Hoc

Purpose A significant relationship between verbal short-term memory (STM) and language performance in people with aphasia has been found across studies. However, very few studies have examined the predictive value of verbal STM in treatment outcomes. This study aims to determine if verbal STM can be used as a predictor of treatment success. Method Retrospective data from 25 people with aphasia in a larger randomized controlled trial of phonomotor treatment were analyzed. Digit and word spans from immediately pretreatment were run in multiple linear regression models to determine whether they predict magnitude of change from pre- to posttreatment and follow-up naming accuracy. Pretreatment, immediately posttreatment, and 3 months posttreatment digit and word span scores were compared to determine if they changed following a novel treatment approach. Results Verbal STM, as measured by digit and word spans, did not predict magnitude of change in naming accuracy from pre- to posttreatment nor from pretreatment to 3 months posttreatment. Furthermore, digit and word spans did not change from pre- to posttreatment or from pretreatment to 3 months posttreatment in the overall analysis. A post hoc analysis revealed that only the less impaired group showed significant changes in word span scores from pretreatment to 3 months posttreatment. Discussion The results suggest that digit and word spans do not predict treatment gains. In a less severe subsample of participants, digit and word span scores can change following phonomotor treatment; however, the overall results suggest that span scores may not change significantly. The implications of these findings are discussed within the broader purview of theoretical and empirical associations between aphasic language and verbal STM processing.

Sex differences in antihypertensive drug use and blood pressure control

2019 ◽  
Vol 95 (1124) ◽  
pp. 295-299
Author(s):  
Junwen Wang ◽  
Weihong Jiang ◽  
Manju Sharma ◽  
Yuyan Wu ◽  
Jiayin Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Drug Use ◽  
Antihypertensive Drug ◽  
Antihypertensive Drugs ◽  
Age Groups ◽  
Channel Blockers ◽  
Elderly Age ◽  
Converting Enzyme Inhibitors ◽  
Males And Females

BackgroundHypertension is the most important modifiable cardiovascular risk factor. Epidemiological studies have shown the benefits of lowering blood pressure (BP), but BP control is a major challenge. Furthermore, there are significant sex differences in antihypertensive drug use and BP control. This study examined sex differences in antihypertensive drug use and BP control, with the aim of reducing the complications of hypertension and improving quality of life.MethodsThe study was performed in our outpatient hypertension clinic, and included 1529 patients without secondary hypertension or comorbidities. The study, investigated BP control rates and patterns of antihypertensive drug use in male and female. All data were collected using structured questionnaires and patient measurements.ResultsThe study included 713 males and 816 females in this study. Fewer females had hypertension in the younger age group (16.2% vs 11.6%; p>0.05), but this difference disappeared in middle-aged (47.8% vs 49.9 %; p<0.05) and elderly age groups (36.0% vs 38.5%; p<0.05). BP control rates differed between males and females (35.6% in male, 31.9% in female, p<0.01). There was an overall difference in BP control rates between males and females (35.6% in males, 31.9% in females, p<0.01). In this aged 18–44 years, angiotensin converting enzyme inhibitors (ACEIs) showed the best control rate in males, while calcium channel blockers (CCBs) were least effective (61.5% with ACEIs, 28.6% with CCBs; p<0.05). In this aged 45–64 years, diuretics (DUs) showed the best control rate in females, while CCBs were least effective (47.5% with DUs, 28.3% with CCBs; p<0.05).ConclusionsSex plays an important role in BP control. In those aged 18–44 years, males using ACEIs showed best control rates. In those aged 45–64 years, females using DUs showed best control rates. Our study provides a basis with the selection of antihypertensive drugs according to sex and age.

scholarly journals Empagliflozin for Patients With Presumed Resistant Hypertension: A Post Hoc Analysis of the EMPA-REG OUTCOME Trial

2020 ◽  
Author(s):  
João Pedro Ferreira ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Bettina Johanna Kraus ◽  
Christoph Wanner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Repeated Measures ◽  
Cox Regression ◽  
Antihypertensive Drugs ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Cardiac Events ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract BACKGROUND Type 2 diabetes (T2D) and resistant hypertension often coexist, greatly increasing risk of target-organ damage and death. We explored the effects of empagliflozin in patients with and without presumed resistant hypertension (prHT) in a post hoc analysis of EMPA-REG OUTCOME (NCT01131676). METHODS Overall, 7,020 patients received empagliflozin 10, 25 mg, or placebo with median follow-up of 3.1 years. We defined baseline prHT as ≥3 classes of antihypertensive drugs including a diuretic and uncontrolled blood pressure (BP; systolic blood pressure (SBP) ≥140 and/or diastolic blood pressure ≥90 mm Hg) or ≥4 classes of antihypertensive, including a diuretic, and controlled BP. We explored the effect of empagliflozin on cardiovascular (CV) death, heart failure (HF) hospitalization, 3-point major adverse cardiac events, all-cause death, and incident/worsening nephropathy by Cox regression and BP over time by a mixed-repeated-measures-model analysis. RESULTS 1,579 (22.5%) patients had prHT. The mean difference in change in SBP from baseline to week 12 vs. placebo was −4.5 (95% confidence interval, −5.9 to −3.1) mm Hg (P &lt; 0.001) in prHT and −3.7 (−4.5, −2.9) mm Hg (P &lt; 0.001) in patients without prHT. SBP was more frequently controlled (&lt;130/80 mm Hg) with empagliflozin than with placebo. Patients with prHT had 1.5- to 2-fold greater risk of HF hospitalization, incident/worsening nephropathy, and CV death compared with those without prHT. Empagliflozin improved all outcomes in patients with and without prHT (interaction P &gt; 0.1 for all outcomes). CONCLUSIONS Empagliflozin induced a clinically relevant reduction in SBP and consistently improved all outcomes regardless of prHT status. Due to these dual effects, empagliflozin should be considered for patients with hypertension and T2D.

Differences in the exposure to sunitinib in the immediate and deferred cytoreductive nephrectomy (CN) arms of the randomized controlled trial SURTIME.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 703-703
Author(s):  
Yasmin Abu-Ghanem ◽  
Johannes V. Van Thienen ◽  
Christian U. Blank ◽  
Thomas Powles ◽  
Bertrand F. TOMBAL ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Drug Exposure ◽  
Controlled Trial ◽  
Dose Intensity ◽  
Duration Of Treatment ◽  
Intention To Treat ◽  
Number Of Patients ◽  
Metastatic Sites ◽  
Post Hoc ◽  
Treat Analysis

703 Background: SURTIME compared immediate CN followed by sunitinib 50mg/day (4/2 weeks on-off) 4 weeks after surgery (n=50) versus 3 cycles sunitinib followed by CN in the absence of progression and continued sunitinib 4 weeks after surgery (n=49). In the intention to treat analysis, the hazard ratio of the secondary endpoint overall survival (OS) favored deferred CN [0.57 (CI: 0.34–0.95, p=0.032)] with a median OS of 32.4 (CI: 14.5-65.3) versus only 15.0 months (CI: 9.3–29.5), following immediate CN. We investigated differences in exposure to systemic therapy between the two arms. Methods: Post-hoc exploratory analysis of number of patients receiving sunitinib, overall response rate (ORR) by RECIST 1.1, length of drug exposure and dose intensity in the immediate and deferred arm. Descriptive methods and 95% confidence intervals (CI) were used. Results: In the deferred arm, 97.7% (CI: 89.3-99.6; n=48) received sunitinib versus only 80% (CI: 66.9-88.7, n=40) in the immediate arm. Following immediate CN, 19.6% had confirmed progression at an interval CT scan 4 weeks after CN compared to baseline and 25% started with sunitinib > 4 weeks after surgery. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm versus 32.7% in the deferred arm, who had a per-protocol recommendation against nephrectomy. In the deferred arm, 83% completed 3 cycles sunitinib with 77.1% at >90%-120% relative dose intensity and an ORR of 29%, reducing the median sum of target lesions from 162 to 127 mm prior to planned CN.Of the patients who started with sunitinib in the immediate (n=40) or continued in the deferred arm after CN (n=29) median duration of treatment was 140 versus 351 days. Conclusions: With immediate CN fewer patients receive systemic therapy, which is administered later and shorter compared to the deferred approach. Starting systemic therapy with sunitinib leads to early and more profound control of the disease and identification of progression prior to planned CN which may translate into the observed survival benefit. Clinical trial information: NCT01099423.

Abstract 6265: A Cluster Randomised Controlled Trial of Oscillometric Versus Manual Sphygmomanometers for Blood Pressure Management in Primary Care (CRAB)

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mark R Nelson ◽  
Stephen Quinn ◽  
Linda Bowers-Ingram ◽  
Jan M Nelson ◽  
Tania M Winzenberg
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Controlled Trial ◽  
Intervention Group ◽  
Cluster Randomised Controlled Trial ◽  
Control Group ◽  
Digit Preference ◽  
Oscillometric Device ◽  
Prescribing Behaviour ◽  
Post Hoc

Although mercury sphygmomanometers are seen as the gold standard instrument for blood pressure (BP) measurement they are being withdrawn due to health and safety concerns. This has potential for changes in BP recording and management. CRAB aimed to determine the effect of an oscillometric device on digit preference, BP measurement and antihypertensive drug prescribing. Cluster randomized controlled trial in 24 family practices in Tasmania, Australia. Practices were excluded if they had oscillometric devices. Intervention practices were supplied with OMRON HEM-907 monitors for all clinical rooms and other BP measuring devices were removed. Three practices (2 control & 1 intervention) withdrew. Intervention practices had a 1 week run-in phase for familiarization and novelty reduction. Intervention practices were subsequently audited by a research nurse as prospective collection of data by a family physician may have influenced the outcome measures of interest. Control practice audit periods were matched to intervention practices. All analyses were ITT and adjusted for potential clustering. Differences in BP were analysed using generalised estimating equations. All other outcomes were analysed using multilevel mixed-effects poisson regression. Post hoc analyses were performed to determine the mediators of changes in prescribing behaviour. 3355 records were reviewed with 828 visits having BP recordings. The percentage of BP recordings ending in “0” was significantly lower in intervention vs. control practices [SBP 18% (233/329) vs. 71% (107/587), DBP 20% (229/328) vs. 70% (119/584) p<0.001]. The mean of systolic BP recordings in the intervention group was 7.5 mmHg (95% CI 5.2, 9.9 mmHg) higher than in the control group. Patients taking BP lowering drugs were more likely (IRR 1.3 95% CI 1.1, 1.7) to have a BP lowering drug prescribed if they were in the intervention compared to the control. Post hoc analyses identified systolic BP and not terminal digit preference as mediators of changes in prescribing behaviour. Oscillometric BP devices led to increases in overall prescribing of antihypertensive drugs. This was most likely mediated by reductions in measurement error leading to higher BP recordings.

Abstract 12868: Morphine Decreases Ticagrelor Concentrations but Not Its Effects: A Randomized, Double-Blind, Placebo-Controlled Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Eva-Luise Hobl ◽  
Birgit Reiter ◽  
Thomas Stimpfl ◽  
Christian Schoergenhofer ◽  
Michael Schwameis ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Active Metabolite ◽  
Drug Exposure ◽  
Controlled Trial ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Blood Platelet ◽  
Loading Dose ◽  
Double Blind ◽  
Double Blind Placebo

Introduction: Our recent drug interaction trial with clopidogrel showed that morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in susceptible individuals. This study examined possible drug-drug interactions between ticagrelor and morphine. Hypothesis: We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor. Methods: Twenty-four healthy subjects received a loading dose of 180mg ticagrelor together with placebo or 5mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor effects were measured by platelet function tests. Results: Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (p<0.05) by one hour and decreases plasma levels of ticagrelor and its active metabolite (by 25-31%; p < 0.03) and the drug exposure (area under the curve by 22-23%; p < 0.01). Importantly, however, the effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation, and vasodilator-stimulated phosphoprotein (VASP) phosphorylation are not affected by morphine. Conclusions: Morphine co-administration moderately decreases ticagrelor plasma concentrations but does not inhibit ist effects. Therefore, a 180 mg loading dose of ticagrelor appears to provide consistent and reliable platelet inhibition when morphine has to be given for pain relief.

scholarly journals Resistant hypertension improved after 3 months by measuring drug levels to identify non-adherence

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L E J Peeters ◽  
M H W Kappers ◽  
D A Hesselink ◽  
J B Van Der Net ◽  
S C C Hartong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Antihypertensive Drugs ◽  
Controlled Trial ◽  
Blood Pressure Measurement ◽  
Primary Objective ◽  
Therapeutic Drug ◽  
Personalized Feedback ◽  
Drug Levels

Abstract Introduction Identification of non-adherence to antihypertensive drugs is crucial to improve resistant hypertension (RH). For this therapeutic drug monitoring is the most reliable method. Purpose The primary objective of this analysis is to determine whether drug levels measured with a dried blood spot (DBS) method combined with personalized feedback leads to a decrease in prevalence of RH after 3 months due to an increase in adherence. Methods This is a multi-centre single-blinded randomized controlled trial (RHYME-RCT, NL6736). Patients went to an eligibility visit, where DBS sampling and a 24-hour ambulatory blood pressure measurement (ABPM) was performed simultaneously. Patients with a daytime systolic blood pressure (SBP) &gt;135 and/or diastolic blood pressure (DBP) &gt;85 mmHg were randomized to standard treatment (control) or intervention. The intervention was performed by the treating physician and included information on drug levels and a personalized feedback conversation based on a feedback tool. The follow-up period was one year and included visits at 3, 6 and 12 months after the eligibility visit. At each visit an ABPM and DBS were performed. Results A total of 53 patients (mean age of 59±11 years, 78.7% male) with at least three months of follow-up were included. The prevalence of RH decreased from 100% in both arms to 75.0% in the intervention arm (p=0.014, n=24) and 58.6% in the control arm (p=0.001, n=29). No improvements were seen in adherence rates over time. Furthermore, no significant differences were found after three months between the two groups in the degree of RH (p=0.214), SBP (p=0.551) or adherence (p=0.746). Conclusion Measuring blood pressure and drug levels led to a decrease in the prevalence of RH. However, this improvement could not be linked to the actual intervention or improvement of adherence. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMW

scholarly journals Renal Denervation After Symplicity HTN-3 – Back to Basics. Review of the Evidence

2014 ◽  
Vol 9 (2) ◽  
pp. 110 ◽  
Author(s):  
Alexandre Persu ◽  
Fadl Elmula M Fadl Elmula ◽  
Yu Jin ◽  
Ingrid Os ◽  
Sverre E Kjeldsen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Antihypertensive Drugs ◽  
Controlled Trial ◽  
Blood Pressure Reduction ◽  
Renal Sympathetic Denervation ◽  
Drug Adherence ◽  
Regression To The Mean ◽  
Blood Pressure Lowering Effect ◽  
Blood Pressure Elevation

Renal sympathetic denervation (RDN) has been proposed as a new treatment modality in patients with apparent treatment resistant hypertension, a condition defined as office blood pressure elevation despite prescription of at least three antihypertensive drugs including a diuretic. However, the impressive fall in blood pressure reported after RDN in Symplicity HTN-2, the first randomised study, and multiple observational studies has not been confirmed in the US sham-controlled trial Symplicity HTN-3 and four subsequent prospective randomised studies, all published or presented in 2014. The blood pressure reduction documented in earlier studies may be largely due to non-specific effects such as improvement of drug adherence in initially poorly adherent patients (Hawthorne effect), placebo effect and regression to the mean. The overall blood pressure lowering effect of RDN seems rather limited and the characteristics of true responders remain largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with apparent drug-resistant hypertension, drug monitoring and subsequent improvement of drug adherence may prove more effective and cost-beneficial to achieve blood pressure control. In the meantime, research should aim at identifying characteristics of those few patients adherent to drug treatment and with true resistant hypertension who may respond to RDN.

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