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1.
Differential effects of renin-angiotensine-aldosteron system inhibition, sympathoinhibition and low sodium diet on blood pressure in women with a history of preeclampsia: A double-blind, placebo-controlled cross-over trial (the PALM study).
Zoet, GA, Paauw, ND, Veerbeek, JHW, Groenhof, TKJ, Spiering, W, Verhaar, MC, Franx, A, Titia Lely, A
Pregnancy hypertension. 2022;:173-175
Abstract
Current guidelines lack sufficient evidence to recommend a specific blood pressure lowering strategy to prevent cardiovascular disease after preeclampsia. We conducted a double-blind cross-over trial to identify the most potent antihypertensive strategy: renin-angiotensin-aldosterone system (RAAS) inhibition (losartan), sympathoinhibition (moxonidine), low sodium diet and placebo (n = 10). Due to low inclusion rate our study stopped prematurely. Initiatory analyses showed no significant effect of antihypertensive strategy on office blood pressure and 24-hour blood pressure. However, nocturnal dipping was significantly higher on RAAS inhibition and low sodium diet compared to placebo and sympathoinhibition. Optimal cardiovascular prevention after preeclampsia should be further explored.
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2.
Prevention and management of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors.
Weinstein, J, Girard, LP, Lepage, S, McKelvie, RS, Tennankore, K
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2021;(48):E1836-E1841
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3.
Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.
Elkappany, S, Hashem, A, Elkarta, A, Sheashaa, H, Osman, Y, Shokeir, AA
BJU international. 2020;(6):715-721
Abstract
OBJECTIVES To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. MATERIALS AND METHODS This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25 mg or placebo for 3 months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3 months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3 months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. RESULTS A total of 76 patients completed 3 months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). CONCLUSIONS In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.
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4.
Combined treatment with valsartan and fluvastatin to delay disease progression in nonpermanent atrial fibrillation with hypertension: A clinical trial.
Zhao, Z, Yang, Y, Wang, J, Dong, Z, Niu, X, Liu, E, Liu, T, Li, L, Liang, Y, Li, G
Clinical cardiology. 2020;(12):1592-1600
Abstract
BACKGROUND Atrial fibrillation (AF) is a complex cardiac arrhythmia in clinical practice with increasing incidence. However, the effects of statins on patients with AF are not quite clear. HYPOTHESIS To investigate the protective effect of calcium channel blocker (CCB) and valsartan combined fluvastatin on hypertension (HTN) patients with nonpermanent AF. METHODS In three and a half years, 189 cases of patients diagnosed as HTN combining nonpermanent AF by eight medical centers, were recruited and randomly assigned to four groups with varied treatments: CCB group; CCB + statin group; valsartan group; and valsartan + statin group. The four groups were followed up for 24 months. The 7-day Holter ultrasound echocardiography (UCG) and biochemical indexes were completed at preset time nodes respectively. RESULTS After 24 months of follow-up, 178 patients completed the study. Compared with CCB group, the blood lipid level, inflammatory index, ultrasonic index and electrocardiographic measurement results of CCB + statin group, valsartan group and valsartan + statin group were improved in different degrees and had statistical significance (P < .05 or P < .01). Furthermore, the improvement trend of CCB + statin group and valsartan + statin group was more obvious. CONCLUSIONS The results indicated that valsartan can reduce AF load and recurrence rate, and delay the progression of nonpermanent AF to permanent AF in multiple ways, and the effect of combination of valsartan and fluvastatin is more significant. These results provide a new direction for the integrated upstream control strategy of AF.
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5.
Angiotensin Type 1 Receptor Blockers in Heart Failure.
Singh, KD, Karnik, SS
Current drug targets. 2020;(2):125-131
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Abstract
Homeostasis in the cardiovascular system is maintained by physiological functions of the Renin Angiotensin Aldosterone System (RAAS). In pathophysiological conditions, over activation of RAAS leads to an increase in the concentration of Angiotensin II (AngII) and over activation of Angiotensin Type 1 Receptor (AT1R), resulting in vasoconstriction, sodium retention and change in myocyte growth. It causes cardiac remodeling in the heart which results in left ventricular hypertrophy, dilation and dysfunction, eventually leading to Heart Failure (HF). Inhibition of RAAS using angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) has shown to significantly reduce morbidity and mortality due to HF. ACEi have been shown to have higher drug withdrawal rates due to discomfort when compared to ARBs; therefore, ARBs are the preferred choice of physicians for the treatment of HF in combination with other anti-hypertensive agents. Currently, eight ARBs have been approved by FDA and are clinically used. Even though they bind to the same site of AT1R displacing AngII binding but clinical outcomes are significantly different. In this review, we described the clinical significance of each ARB in the treatment of HF and their clinical outcome.
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Comparison of the Effect of Sacubitril/Valsartan on Left Ventricular Systolic Function in Patients with Non-ischaemic and Ischaemic Cardiomyopathy.
Ioannou, A, Metaxa, S, Simon, S, Mandal, AKJ, Missouris, CG
Cardiovascular drugs and therapy. 2020;(6):755-762
Abstract
PURPOSE Sacubitril/valsartan has been demonstrated to improve prognosis and outcomes in heart failure with reduced ejection fraction (HFrEF) patients. We sought to compare the improvement in cardiac function between non-ischaemic and ischaemic cardiomyopathy for patients receiving sacubitril/valsartan. METHODS We conducted a single centre prospective cohort survey of patients reviewed in the Heart Function Clinic between February 2017 and January 2018. Functional evaluation and measurement of biochemical and echocardiographic parameters occurred before the initiation of sacubitril/valsartan, and after 3 months of treatment. RESULTS We identified 52 patients (26 non-ischaemic and 26 ischaemic cardiomyopathy) suitable for treatment with sacubitril/valsartan. Treatment was followed by a significant decrease in a New York Heart Association (NYHA) class in both patients with non-ischaemic (2.3 ± 0.6 vs. 1.6 ± 0.7, P < 0.001) and ischaemic cardiomyopathy (2.3 ± 0.5 vs. 1.5 ± 0.6, P < 0.001), along with an increase in ejection fraction in both patients with non-ischaemic (26.2% ± 6.5% vs. 37.2% ± 13.8%, P < 0.001) and ischaemic cardiomyopathy (28.1% ± 5.7% vs. 31.5% ± 8.4%, P = 0.007). The improvement in ejection fraction was significantly greater in the patients with non-ischaemic cardiomyopathy compared to those with ischaemic cardiomyopathy (10.7% ± 13.0% vs. 3.9% ± 6.0%, P = 0.023). CONCLUSION Our study suggests that treatment with sacubitril/valsartan in patients with non-ischaemic cardiomyopathy is followed by a greater improvement in ejection fraction than in patients with ischaemic cardiomyopathy.
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Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction.
Kuno, T, Ueyama, H, Fujisaki, T, Briasouli, A, Takagi, H, Briasoulis, A
The American journal of cardiology. 2020;(8):1187-1193
Abstract
Clinical trials of renin-angiotensin-aldosterone system (RAAS) antagonists in heart failure with preserved ejection fraction (HFpEF) have suggested neutral results and treatment is focused on associated symptoms and comorbidities. MEDLINE and EMBASE were searched through October 2019 for randomized controlled studies investigating the effects of different RAAS antagonists in patients with HFpEF. The main outcomes were all-cause mortality, trial defined cardiovascular mortality, and heart failure (HF) hospitalizations. To compare different RAAS antagonists, a random-effects restricted-maximum-likelihood network meta-analysis based on a frequentist framework for indirect and mixed comparisons was used. We used p scores to rank best treatments per outcome. Our search identified 5 eligible clinical trials (PEP-CHF, perindopril; CHARM-preserved, candesartan; I-PRESERVE, irbesartan; TOPCAT, spironolactone; PARAGON-HF, sacubitril-valsartan and valsartan) enrolling a total 10,523 on RAAS antagonists and 6,259 controls. We did not identify any statistical difference in all-cause and cardiovascular mortality among RAAS antagonists and placebo. The combination of sacubitril-valsartan was associated with significantly decreased HF hospitalization risk compared with controls (odds ratio 0.73, 95% confidence interval 0.61 to 0.87) and angiotensin II receptor blockers (odds ratio 0.80, 95% confidence interval 0.71 to 0.91), without heterogeneity among studies (I2 = 0). Angiotensin receptor neprilysin inhibitor (ARNI) ranked better than other RAAS antagonists for HF hospitalizations (p value 0.9). In conclusion, RAAS antagonists do not affect mortality but the combination of sacubitril-valsartan is associated with lower HF hospitalizations in HFpEF patients.
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Prior Heart Failure Hospitalization, Clinical Outcomes, and Response to Sacubitril/Valsartan Compared With Valsartan in HFpEF.
Vaduganathan, M, Claggett, BL, Desai, AS, Anker, SD, Perrone, SV, Janssens, S, Milicic, D, Arango, JL, Packer, M, Shi, VC, et al
Journal of the American College of Cardiology. 2020;(3):245-254
Abstract
BACKGROUND The period shortly after hospitalization for heart failure (HF) represents a high-risk window for recurrent clinical events, including rehospitalization or death. OBJECTIVES This study sought to determine whether the efficacy and safety of sacubitril/valsartan varies in relation to the proximity to hospitalization for HF among patients with HF with preserved ejection fraction (HFpEF). METHODS In this post hoc analysis of PARAGON-HF (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ARB [Angiotensin Receptor Blocker] Global Outcomes in HFpEF), we assessed the risk of clinical events and response to sacubitril/valsartan in relation to time from last HF hospitalization among patients with HFpEF (≥45%). The primary outcome was composite total HF hospitalizations and cardiovascular death, analyzed by using a semiparametric proportional rates method, stratified by geographic region. RESULTS Of 4,796 validly randomized patients in PARAGON-HF, 622 (13%) were screened during hospitalization or within 30 days of prior hospitalization, 555 (12%) within 31 to 90 days, 435 (9%) within 91 to 180 days, and 694 (14%) after 180 days; 2,490 (52%) were never previously hospitalized. Over a median follow-up of 35 months, risk of total HF hospitalizations and cardiovascular death was inversely and nonlinearly associated with timing from prior HF hospitalization (p < 0.001). There was a gradient in relative risk reduction in primary events with sacubitril/valsartan from patients hospitalized within 30 days (rate ratio: 0.73; 95% confidence interval: 0.53 to 0.99) to patients never hospitalized (rate ratio: 1.00; 95% confidence interval: 0.80 to 1.24; trend in relative risk reduction: pinteraction = 0.15). With valsartan alone, the rate of total primary events was 26.7 (≤30 days), 24.2 (31 to 90 days), 20.7 (91 to 180 days), 15.7 (>180 days), and 7.9 (not previously hospitalized) per 100 patient-years. Compared with valsartan, absolute risk reductions with sacubitril/valsartan were more prominent in patients enrolled early after hospitalization: 6.4% (≤30 days), 4.6% (31 to 90 days), and 3.4% (91 to 180 days), whereas no risk reduction was observed in patients screened >180 days or who were never hospitalized (trend in absolute risk reduction: pinteraction = 0.050). CONCLUSIONS Recent hospitalization for HFpEF identifies patients at high risk for near-term clinical progression. In the PARAGON-HF trial, the relative and absolute benefits of sacubitril/valsartan compared with valsartan in HFpEF appear to be amplified when initiated in the high-risk window after hospitalization and warrant prospective validation. (PARAGON-HF; NCT01920711).
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Effects of sartans and low-dose statins on cerebral white matter hyperintensities and cognitive function in older patients with hypertension: a randomized, double-blind and placebo-controlled clinical trial.
Zhang, H, Cui, Y, Zhao, Y, Dong, Y, Duan, D, Wang, J, Sheng, L, Ji, T, Zhou, T, Hu, W, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2019;(5):717-729
Abstract
Cerebral white matter hyperintensities (WMHs) and cognitive impairment are common in elderly hypertensive patients, and more needs to be learned about their prevention and treatment. Our aim was to investigate the effect of low-dose statins on WMH and cognitive function in elderly patients undergoing antihypertensive treatment. A total of 732 elderly hypertensive patients taking hydrochlorothiazide as their baseline medication were randomized using a 2 × 2 factorial design with antihypertensive (telmisartan vs. placebo) and lipid-modulating (low-dose rosuvastatin vs. placebo) arms. Brain magnetic resonance imaging (MRI) and cognitive function data were obtained. After a mean follow-up time of 59.8 (range 12-65) months, there were no differences in WMH progression and cognitive function decline over time between the groups in the antihypertensive arm. The risks of new-incident WMH Fazekas scale scores ≥ 2 and the incidence of cognitive impairment did not differ between the telmisartan and placebo groups. Rosuvastatin use was associated with lower risks of new-incident Fazekas scale scores ≥2 (hazard ratio = 0.500; 95% confidence interval: 0.34-0.74) and cognitive impairment (hazard ratio = 0.54; 95% confidence interval: 0.36-0.80). Telmisartan interacted with rosuvastatin on reducing WMH progression and cognitive function decline. Findings suggest that low-dose rosuvastatin could reduce WMH progression and cognitive function decline in antihypertensive patients, as demonstrated by the interaction between telmisartan and low-dose rosuvastatin to this effect.
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10.
Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.
Imaizumi, S, Shiga, Y, Ogawa, M, Sako, H, Nagata, Y, Matsunaga, A, Shirotani, T, Hoshino, F, Yahiro, E, Uehara, Y, et al
Heart and vessels. 2019;(4):698-710
Abstract
There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.