scholarly journals Association Between Physical Status and the Effects of Combination Therapy With Renin-Angiotensin System Inhibitors and β-Blockers in Patients With Acute Heart Failure

2021 ◽  
Vol 3 (4) ◽  
pp. 217-226
Author(s):  
Kensuke Takabayashi ◽  
Shouji Kitaguchi ◽  
Takashi Yamamoto ◽  
Ryoko Fujita ◽  
Kotoe Takenaka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Combination Therapy ◽  
Acute Heart Failure ◽  
Renin Angiotensin System ◽  
Physical Status ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Β Blockers

Long-Term Adherence to Renin–Angiotensin System Inhibitors and β-Blockers After Heart Failure Hospitalization in Senior Patients

2020 ◽  
Vol 25 (6) ◽  
pp. 531-540
Author(s):  
Xiwen Qin ◽  
Joseph Hung ◽  
Tiew-Hwa Katherine Teng ◽  
Tom Briffa ◽  
Frank M. Sanfilippo
Keyword(s):  
Heart Failure ◽  
Medication Adherence ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Β Blocker ◽  
Β Blockers ◽  
Senior Patients

Aims: We investigated long-term adherence to renin–angiotensin system inhibitors (RASIs) and β-blockers, and associated predictors, in senior patients after hospitalization for heart failure (HF). Methods: A population-based data set identified 4488 patients who survived 60 days following their index hospitalization for HF in Western Australia from 2003 to 2008 with a 3-year follow-up. Their person-linked Pharmaceutical Benefits Scheme records identified medications dispensed during follow-up. Drug discontinuation was defined as the first break ≥90 days following the previous supply. Medication adherence was calculated using the proportion of days covered (PDC), with PDC ≥ 80% defined as being adherent. Multivariable logistic regression models were used to identify predictors of PDC < 80%. Results: In the cohort (57% male, mean age: 76.6 years), 77.4% were dispensed a RASI and 52.7% a β-blocker within 60 days postdischarge. Over the 3-year follow-up, 28% and 42% of patients discontinued RASI and β-blockers, respectively. Only 64.6% and 47.5% of RASI and β-blocker users, respectively, were adherent to their treatment over 3 years, with adherence decreasing over time (trend P < .0001 for RASI and trend P = .02 for β-blockers). Older age, increasing Charlson comorbidity score, chronic kidney disease, and chronic obstructive pulmonary disease were independent predictors of PDC < 80% for both drug groups. Conclusion: Among seniors hospitalized for HF, discontinuation gaps were common for RASI and β-blockers postdischarge, and long-term adherence to these medications was suboptimal. Where appropriate, strategies to improve long-term medication adherence are indicated in HF patients, particularly in elderly patients with comorbidities.

scholarly journals Risk of Developing Hypokalemia in Patients With Hypertension Treated With Combination Antihypertensive Therapy

Hypertension ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 966-972 ◽  
Author(s):  
Maria Lukács Krogager ◽  
Rikke Nørmark Mortensen ◽  
Peter Enemark Lund ◽  
Henrik Bøggild ◽  
Steen Møller Hansen ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Calcium Channel ◽  
Antihypertensive Therapy ◽  
Calcium Channel Blockers ◽  
Odds Ratio ◽  
Renin Angiotensin System ◽  
Channel Blockers ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Β Blockers

Little is known about the occurrence of hypokalemia due to combination therapy for hypertension. Using data from Danish administrative registries, we investigated the association between different combinations of antihypertensive therapy and risk of developing hypokalemia. Using incidence density matching, 2 patients without hypokalemia were matched to a patient with hypokalemia (K, <3.5 mmol/L) on age, sex, renal function, and time between index date and date of potassium measurement. Combination therapies were subdivided into 10 groups including β-blockers (BB)+thiazides (BB+thiazides), calcium channel blockers (CCB)+renin angiotensin system inhibitors (RASi)+thiazides (CCB+RASi+Thiazides), calcium channel blockers+thiazides (CCB+thiazides), and β-blockers+renin angiotensin system inhibitors+thiazides (BB+RASi+thiazides). We used conditional logistic regression to estimate the odds of developing hypokalemia for different combinations of antihypertensive drugs within 90 days of combination therapy initiation. We matched 463 patients with hypokalemia to 926 patients with normal potassium concentrations. The multivariable analysis showed 5.82× increased odds of developing hypokalemia if administered CCB+thiazides (95% CI, 3.06–11.08) compared with CCB+RASi. Other combinations significantly associated with increased hypokalemia odds were BB+thiazides (odds ratio, 3.34 [95% CI, 1.67–6.66]), CCB+RASi+thiazides (odds ratio, 3.07 [95% CI, 1.72–5.46]), and BB+RASi+thiazides (odds ratio, 2.78 [95% CI, 1.41–5.47]). Combinations of thiazides with CCB, RASi, or BB were strongly associated with increased hypokalemia risk within 90 days of treatment initiation.

scholarly journals Impact of sex-specific target dose in chronic heart failure patients with reduced ejection fraction

2020 ◽  
pp. 204748732092318
Author(s):  
Jesse F Veenis ◽  
Hans-Peter Brunner-La Rocca ◽  
Gerard CM Linssen ◽  
Ayten Erol-Yilmaz ◽  
Arjen CB Pronk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Renin Angiotensin System ◽  
Target Dose ◽  
Dosing Schedule ◽  
Angiotensin System ◽  
Men And Women ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction ◽  
Β Blockers

Aims A recent study suggested that women with heart failure and heart failure reduced ejection fraction might hypothetically need lower doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers ( = renin-angiotensin-system inhibitors) and β-blockers than men to achieve the best outcome. We assessed the current medical treatment of heart failure reduced ejection fraction in men and women in a large contemporary cohort and address the hypothetical impact of changing treatment levels in women. Methods This analysis is part of a large contemporary quality of heart failure care project which includes 5320 (64%) men and 3003 (36%) women with heart failure reduced ejection fraction. Detailed information on heart failure therapy prescription and dosage were collected. Results Women less often received renin-angiotensin-system inhibitors (79% vs 83%, p < 0.01), but more often β-blockers (82% vs 79%, p < 0.01) than men. Differences in guideline-recommended target doses between sexes were relatively small. Implementing a hypothetical sex-specific dosing schedule (at 50% of the current recommended dose in the European Society of Cardiology guidelines in women only) would lead to significantly higher levels of women receiving appropriate dosing (β-blocker 87% vs 54%, p < 0.01; renin-angiotensin-system inhibitor 96% vs 75%, p < 0.01). Most interestingly, the total number of women with >100% of the new hypothetical target dose would be 24% for β-blockers and 52% for renin-angiotensin-system inhibitors, which can be considered as relatively overdosed. Conclusion In this large contemporary heart failure registry, there were significant but relatively small differences in drug dose between men and women with heart failure reduced ejection fraction. Implementation of the hypothetical sex-specific target dosing schedule would lead to considerably more women adequately treated. In contrast, we identified a group of women who might have been relatively overdosed with increased risk of side-effects and intolerance.

scholarly journals A novel role for miR-133a in centrally mediated activation of the renin-angiotensin system in congestive heart failure

2017 ◽  
Vol 312 (5) ◽  
pp. H968-H979 ◽  
Author(s):  
Neeru M. Sharma ◽  
Shyam S. Nandi ◽  
Hong Zheng ◽  
Paras K. Mishra ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Paraventricular Nucleus ◽  
Renin Angiotensin System ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

An activated renin-angiotensin system (RAS) within the central nervous system has been implicated in sympathoexcitation during various disease conditions including congestive heart failure (CHF). In particular, activation of the RAS in the paraventricular nucleus (PVN) of the hypothalamus has been recognized to augment sympathoexcitation in CHF. We observed a 2.6-fold increase in angiotensinogen (AGT) in the PVN of CHF. To elucidate the molecular mechanism for increased expression of AGT, we performed in silico analysis of the 3′-untranslated region (3′-UTR) of AGT and found a potential binding site for microRNA (miR)-133a. We hypothesized that decreased miR-133a might contribute to increased AGT in the PVN of CHF rats. Overexpression of miR-133a in NG108 cells resulted in 1.4- and 1.5-fold decreases in AGT and angiotensin type II (ANG II) type 1 receptor (AT1R) mRNA levels, respectively. A luciferase reporter assay performed on NG108 cells confirmed miR-133a binding to the 3′-UTR of AGT. Consistent with these in vitro data, we observed a 1.9-fold decrease in miR-133a expression with a concomitant increase in AGT and AT1R expression within the PVN of CHF rats. Furthermore, restoring the levels of miR-133a within the PVN of CHF rats with viral transduction resulted in a significant reduction of AGT (1.4-fold) and AT1R (1.5-fold) levels with a concomitant decrease in basal renal sympathetic nerve activity (RSNA). Restoration of miR-133a also abrogated the enhanced RSNA responses to microinjected ANG II within the PVN of CHF rats. These results reveal a novel and potentially unique role for miR-133a in the regulation of ANG II within the PVN of CHF rats, which may potentially contribute to the commonly observed sympathoexcitation in CHF. NEW & NOTEWORTHY Angiotensinogen (AGT) expression is upregulated in the paraventricular nucleus of the hypothalamus through posttranscriptional mechanism interceded by microRNA-133a in heart failure. Understanding the mechanism of increased expression of AGT in pathological conditions leading to increased sympathoexcitation may provide the basis for the possible development of new therapeutic agents with enhanced specificity.

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