Blood pressure lowering efficacy of renin inhibitors for primary hypertension.
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ABSTRACT:
SUBMITTER: Musini VM
PROVIDER: S-EPMC6478238 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Blood pressure lowering efficacy of renin inhibitors for primary hypertension.
Musini Vijaya M VM Lawrence Kendra Ak KA Fortin Patricia M PM Bassett Ken K Wright James M JM
The Cochrane database of systematic reviews 20170405
<h4>Background</h4>Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II.<h4>Objectives</h4>To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in th ...[more]
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Project description:BackgroundRenin inhibitors (RIs) reduce blood pressure more than placebo, with the magnitude of this effect thought to be similar to that for angiotensin converting enzyme (ACE) inhibitors. However, a drug's efficacy in lowering blood pressure cannot be considered as a definitive indicator of its effectiveness in reducing mortality and morbidity. The effectiveness and safety of RIs compared to ACE inhibitors in treating hypertension is unknown.ObjectivesTo evaluate the benefits and harms of renin inhibitors compared to ACE inhibitors in people with primary hypertension.Search methodsThe Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to August 2020: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions.Selection criteriaWe included randomized, active-controlled, double-blinded studies (RCTs) with at least four weeks follow-up in people with primary hypertension, which compared renin inhibitors with ACE inhibitors and reported morbidity, mortality, adverse events or blood pressure outcomes. We excluded people with proven secondary hypertension.Data collection and analysisTwo review authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis.Main resultsWe include 11 RCTs involving 13,627 participants, with a mean baseline age from 51.5 to 74.2 years. Follow-up duration ranged from four weeks to 36.6 months. There was no difference between RIs and ACE inhibitors for the outcomes: all-cause mortality: risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.18; 5 RCTs, 5962 participants; low-certainty evidence; total myocardial infarction: RR 0.86, 95% CI 0.22 to 3.39; 2 RCTs, 957 participants; very low-certainty evidence; adverse events: RR 0.98, 95% CI 0.93 to 1.03; 10 RTCs, 6007 participants; moderate-certainty evidence; serious adverse events: RR 1.21, 95% CI 0.89 to 1.64; 10 RTCs, 6007 participants; low-certainty evidence; and withdrawal due to adverse effects: RR 0.85, 95% CI 0.68 to 1.06; 10 RTCs, 6008 participants; low-certainty evidence. No data were available for total cardiovascular events, heart failure, stroke, end-stage renal disease or change in heart rate. Low-certainty evidence suggested that RIs reduced systolic blood pressure: mean difference (MD) -1.72, 95% CI -2.47 to -0.97; 9 RCTs, 5001 participants; and diastolic blood pressure: MD -1.18, 95% CI -1.65 to -0.72; 9 RCTs, 5001 participants, to a greater extent than ACE inhibitors, but we judged this to be more likely due to bias than a true effect. AUTHORS' CONCLUSIONS: For the treatment of hypertension, we have low certainty that renin inhibitors (RI) and angiotensin converting enzyme (ACE) inhibitors do not differ for all-cause mortality and myocardial infarction. We have low to moderate certainty that they do not differ for adverse events. Small reductions in blood pressure with renin inhibitors compared to ACE inhibitors are of low certainty. More independent, large, long-term trials are needed to compare RIs with ACE inhibitors, particularly assessing morbidity and mortality outcomes, but also on blood pressure-lowering effect.
| S-EPMC8094968 | biostudies-literature
Project description:BackgroundTriamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied.ObjectiveTo determine if triamterene provides an effect to further lower BP in patients treated with HCTZ.DesignWe conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012.Main measuresBP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses.Key resultsThe mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications.ConclusionsIn the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.
| S-EPMC4700022 | biostudies-literature
Project description:AbstractWaon therapy (WT) has been used as a thermal therapy in chronic heart failure patients. However, its effect in patients with hypertension is unclear. This study aimed to reveal the hypotensive effect of WT in patients with hypertension. WT was performed on 31 patients with hypertension (63.9 ± 11.9 years, male: 17) on standard hypertension treatment focusing on lifestyle modification and medication. Systolic and diastolic blood pressures were measured before and after WT using an upper arm automated sphygmomanometer. We investigated the effect of single and repeated (1 time/d, >5 times) WT sessions on blood pressure and further compared its effect between current smoking (n = 11, 55.4 ± 6.4 years, 8.5 ± 2.4 times) and non-smoking (n = 11, 66.9 ± 8.5 years, 12.2 ± 5.9 times) groups. A total of 370 sessions of WT were conducted. Systolic and diastolic blood pressures significantly decreased after a single WT session (systolic blood pressure: 118.5 ± 10.1 to 115.1 ± 9.0 mm Hg, P < .001; diastolic blood pressure: 70.5 ± 6.4 to 65.9 ± 5.3 mm Hg, P < .001). The blood pressure decrease following repeated WT was not significant when all participants were considered (systolic blood pressure: 122.3 ± 15.2 to 116.9 ± 19.6 mm Hg; diastolic blood pressure: 73.8 ± 16.7 to 68.2 ± 13.2 mm Hg); however, it was significant in the non-smoking group (systolic blood pressure: 124.2 ± 11.3 to 108.8 ± 13.4 mm Hg, P < .001; diastolic blood pressure: 73.6 ± 4.9 to 62.1 ± 7.6 mm Hg, P < .001). Repeated WT (at least 5 sessions) decreased blood pressure in patients with hypertension, especially in non-smokers. WT is a simple method to reduce blood pressure in non-smoking patients with hypertension.
| S-EPMC8202594 | biostudies-literature
Project description:Recent guidelines call for more intensive blood pressure (BP)-lowering and a less-stringent treatment-resistant hypertension (TRH) definition, both of which may increase the occurrence of this high-risk phenotype. We performed a post hoc analysis of 11 784 SPRINT and ACCORD-BP participants without baseline TRH, who were randomized to an intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP target. Incidence, prevalence, and predictors of TRH were compared using the updated definition (requiring ≥4 drugs to achieve BP < 130/80 mm Hg) during intensive treatment, vs the former definition (requiring ≥4 drugs to achieve BP < 140/90 mm Hg) during standard treatment. Incidence/prevalence of apparent refractory hypertension (RFH; uncontrolled BP despite ≥5 drugs) was similarly compared. Overall, 5702 and 6082 patients were included in the intensive and standard treatment cohorts, respectively. Crude TRH incidence using the updated definition under intensive treatment was 30.3 (95% CI, 29.3-31.4) per 100 patient-years, compared with 9.7 (95% CI, 9.2-10.2) using the prior definition under standard treatment. Point prevalence using the prior TRH definition at 1-year was 7.5% in SPRINT and 14% in ACCORD vs 22% and 36%, respectively, with the updated TRH definition. Significant predictors of incident TRH included number of baseline antihypertensive drugs, having diabetes, baseline systolic BP, and Black race. Incidence of apparent RFH was also significantly greater using the updated vs prior definition (4.5 vs 1.0 per 100 person-years). Implementation of the 2017 hypertension guideline, including lower BP goals for most individuals, is expected to substantially increase treatment burden and incident TRH among the hypertensive population.
| S-EPMC6565478 | biostudies-literature
Project description:BackgroundIt is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population.MethodsThis analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate.ResultsAmong SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively).ConclusionsAmong patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
| S-EPMC5538944 | biostudies-literature
Project description:BackgroundThe renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population.MethodsA total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study. Twenty-seven BP measurements were taken using random-zero sphygmomanometers at baseline and 2 follow-up visits. Mixed-effect models were used to assess the additive associations of 106 single-nucleotide polymorphisms (SNPs) in 10 RAAS genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. Attempts were made to replicate significant findings among Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). False discovery rate procedures were used to adjust for multiple testing.ResultsDuring an average of 7.2 years of follow-up, average systolic and diastolic BP increased, and 32.1% (512) of participants free from hypertension at baseline developed hypertension. NR3C2 SNPs rs7694064 and rs6856803 were significantly associated with longitudinal changes in systolic BP (P interaction = 6.9×10(-5) and 8.2×10(-4), respectively). Through gene-based analysis, NR3C2 was found to be significantly associated with longitudinal systolic BP change (P value of 1.00×10(-7)), even after removal of significant markers rs7694064 and rs6856803 from the analysis. The association between NR3C2 and longitudinal systolic BP change was replicated in Asian MESA participants (P value of 1.00×10(-4)).ConclusionsThese findings indicate that NR3C2 may play an important role in BP progression and development of hypertension.
| S-EPMC4715244 | biostudies-literature
Project description:Hypertension is proved to be associated with severity and mortality in coronavirus disease 2019 (COVID-19). However, little is known about the effects of pre-admission and/or in-hospital antihypertension treatments on clinical outcomes. Thus, this study aimed to investigate the association between in-hospital blood pressure (BP) control and COVID-19-related outcomes and to compare the effects of different antihypertension treatments. This study included 2864 COVID-19 patients and 1628 were hypertensive. Patients were grouped according to their BP during hospitalization and records of medication application. Patients with higher BP showed worse cardiac and renal functions and clinical outcomes. After adjustment, subjects with pre-admission usage of renin-angiotensin-aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14-0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission. Particularly, hypertension patients receiving RAAS inhibitor treatment either before (HR = 0.35, 95%CI 0.13-0.97, P = .043) or after (HR = 0.18, 95%CI 0.04-0.86, P = .031) admission showed a significantly lower risk of adverse clinical outcomes than those receiving application of other antihypertensive medicines. Furthermore, consecutive application of RAAS inhibitors in COVID-19 patients with hypertension showed better clinical outcomes (HR = 0.10, 95%CI 0.01-0.83, P = .033) than non-RAAS inhibitors users. We revealed that COVID-19 patients with poor BP control during hospitalization had worse clinical outcomes. Compared with other antihypertension medicines, RAAS inhibitors were beneficial for improving clinical outcomes in COVID-19 patients with hypertension. Our findings provide direct evidence to support the administration of RAAS inhibitors to COVID-19 patients with hypertension before and after admission.
| S-EPMC7537535 | biostudies-literature
Project description:Using data from the large-scale HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) study, we investigated the characteristics of the effects of olmesartan-based treatment on morning hypertension in Asian hypertensive patients. Specifically, we investigated the relationship between baseline blood pressure (BP) and BP reduction after 16 weeks by linear regression analyses; determinants of BP reduction were also investigated. For both morning home BP (MHBP) and clinic BP (CBP), reduced systolic BP (SBP) after 16 weeks was associated with baseline SBP (P<0.001). The slope of the regression lines was similar for morning home SBP (MHSBP) (-0.744) and clinic SBP (-0.735). Although sex, concomitant diabetes mellitus and concomitant hepatic disease significantly influence the relationship between BP reduction and baseline BP for MHSBP, none were deemed clinically relevant. In conclusion, olmesartan-based treatment robustly reduced baseline high MHBP, similar to CBP, and the effect was associated with baseline BP but unaffected by patient background factors.
| S-EPMC4865473 | biostudies-literature
Project description:Recent technical advances have renewed interest in device-based therapy for the treatment of drug-resistant hypertension. Findings from recent clinical trials regarding the efficacy of electric stimulation of the carotid sinus for the treatment of resistant hypertension are reviewed here. The main goal of this article, however, is to summarize the preclinical studies that have provided insight into the mechanisms that account for the chronic blood pressure-lowering effects of carotid baroreflex activation. Some of the mechanisms identified were predictable and confirmed by experimentation. Others have been surprising and controversial, and resolution will require further investigation. Although feasibility studies have been promising, firm conclusions regarding the value of this device-based therapy for the treatment of resistant hypertension awaits the results of current multicenter trials.
| S-EPMC3085950 | biostudies-literature
Project description:BackgroundIntensive systolic blood pressure (SBP) lowering has been increasingly used; however, its effect on cardiac remodeling remains not fully understood. This secondary analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients trial aims to determine the changes in left ventricular hypertrophy (LVH) that occur in the context of intensive SBP lowering.MethodsA total of 7141 older patients with hypertension were randomly assigned to intensive treatment (SBP target, 110-130 mm Hg) or standard treatment (130-150 mm Hg). LVH was defined according to the Peguero-Lo Presti criteria on a standard 12-lead echocardiogram.ResultsAt baseline, the prevalence of LVH (16.6% versus 16.5%) and the mean Peguero-Lo Presti value (1811 versus 1808 μV) were comparable between the treatment groups. During a median follow-up of 3.24 years, intensive SBP lowering was associated with a significantly lower risk of new LVH occurrence (hazard ratio, 0.76 [95% CI, 0.66-0.89]; P=0.001) and slower progression of the mean Peguero-Lo Presti index value by -23.47 μV/y (95% CI, -34.93 to -12.01; P=0.000). However, the rates of regression of baseline LVH did not differ significantly. Notably, the beneficial effect of intensive SBP lowering in terms of cardiovascular events (hazard ratio, 0.75 [95% CI, 0.59-0.97]) was not markedly attenuated after adjusting for LVH as a time-varying covariate (hazard ratio, 0.76 [95% CI, 0.59-0.97]).ConclusionsIntensive SBP lowering protects against LVH development in older hypertensive patients, however, this favorable effect could not explain most of the reduction in cardiovascular events associated with intensive SBP lowering.
| S-EPMC10424814 | biostudies-literature