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Frontiers in Cardiovascular Medicine 2022To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs),...
INTRODUCTION
To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs), hampering appropriate management. The objective was to perform a narrative review of the most relevant aspects of clinical trials carried out in primary and secondary hypertension.
METHODS
Studies published in PubMed with the following descriptors: clinical trial, antihypertensive drug, children, adolescents were selected. A previous Cochrane review of 21 randomized CTs pointed out the difficulty that statistical analysis could not assess heterogeneity because there were not enough data. A more recent meta-analysis, that applied more stringent inclusion criteria and selected 13 CTs, also concluded that heterogeneity, small sample size, and short follow-up time, as well as the absence of studies comparing drugs of different classes, limit the utility.
RESULTS
In the presented narrative review, including 30 studies, there is a paucity of CTs focusing only on children with primary or secondary, mainly renoparenchymal, hypertension. In trials on angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics, a significant reduction of both SBP and DBP in mixed cohorts of children with primary and secondary hypertension was achieved. However, few studies assessed the effect of antihypertensive drugs on hypertensive organ damage.
CONCLUSIONS
Given the increasing prevalence and undertreatment of hypertension in this age group, innovative solutions including new design, such as '', and optimizing the use of digital health technologies could provide more precise and faster information about the efficacy of each antihypertensive drug class and the potential benefits according to patient characteristics.
PubMed: 36479567
DOI: 10.3389/fcvm.2022.1042190 -
British Journal of Cancer Jan 2023The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association between the use of ACEIs and lung cancer risk.
METHODS
Records from five databases were searched from inception to 26 January 2022. Clinical studies involving persons aged ≥18 years with at least one year of follow-up and reporting adverse events, including lung cancer, were recorded with separate outcome reports supplied for the ACEIs and control groups. Data were extracted independently by three authors and pooled using a random-effects model. The primary outcome was lung cancer development. Odds ratios (ORs) with 95% confidence intervals (CIs) and lung cancer-related morbidity were calculated.
RESULTS
Of 2400 records screened, 13,061,226 patients were included from seven cohort studies and four case-control studies. Pooled results showed that ACEIs use was linked to increased lung cancer risk (OR 1.19, 95% CI 1.05-1.36; P = 0.008), with high heterogeneity (I = 98%).
CONCLUSIONS
ACEI usage is a greater risk factor for lung carcinogenesis than angiotensin receptor blocker use, especially in Asian patients. Further randomised controlled trials are needed to confirm the causal association between the use of ACEIs and lung cancer risk.
Topics: Humans; Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Risk Factors; Lung Neoplasms; Case-Control Studies
PubMed: 36396817
DOI: 10.1038/s41416-022-02029-5 -
Frontiers in Pharmacology 2022The effect of sacubitril-valsartan (ARNI) in heart failure (HF) patients with mid-range ejection fractions (HFmrEF) remains unclear. This study aimed to investigate the... (Review)
Review
The effect of sacubitril-valsartan (ARNI) in heart failure (HF) patients with mid-range ejection fractions (HFmrEF) remains unclear. This study aimed to investigate the effects of ARNI in HFmrEF patients. From inception to 15 February 2022, articles were searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Whip, and Wanfang databases. Left ventricular functions, indicators related to HF, quality of life score, 6-Minute Walk Test, total effective rate, mortality, readmission rate, and adverse events were the outcomes. Relative risk (RR), weighted mean difference (WMD), and 95% confidence interval (CI) were used to evaluate the outcomes. The heterogeneity test was conducted for each indicator and measured by I statistics. Subgroup analysis was performed regarding the type of study and duration of treatment. Sixteen studies involving 1,937 patients were included in this study. Our results showed ARNI was likely to improve left ventricular function by increasing the left ventricular ejection fraction (LVEF) (WMD: 2.36, 95%CI: 1.09-3.62), stroke volume (WMD: 16.800, 95%CI: 11.385-22.215), and left ventricular short-axis shortening rate (WMD: 2.05, 95%CI: 0.25-3.86), decreasing left ventricular end-diastolic dimension (WMD: -2.48, 95%CI: -3.83 to -1.13), left atrial diameter (WMD: -2.23, 95%CI: -2.83 to -1.63), C-reactive protein level (WMD: -1.40, 95%CI: -2.62 to -0.18), and N-terminal-pro B-type natriuretic peptide level (WMD: -494.92, 95%CI: -641.34 to -348.50). ARNI has a higher total effective rate (RR: 1.15, 95%CI: 1.08-1.21), Kansas City cardiomyopathy questionnaire (WMD: 4.13, 95%CI: 3.46-4.81), and 6-Minute Walk Test (WMD: 51.35, 95%CI: 26.99-75.71) compared with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). In addition, ARNI decreased the readmission rate (RR: 0.54, 95%CI: 0.43-0.68) (all < 0.05). Nevertheless, there were no significant differences in the adverse outcomes. This meta-analysis suggests ARNI may be an effective strategy with which to improve the left ventricular function, and quality of life, and reduce the readmission rate in HFmrEF patients. However, long-term clinical studies with large samples are still needed to further explore the efficacy and safety of ARNI compared with ACEI or ARB in the HFmrEF population.
PubMed: 36353496
DOI: 10.3389/fphar.2022.982372 -
Cardiovascular Diabetology Nov 2022Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the... (Meta-Analysis)
Meta-Analysis
Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF.
METHODS
Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis.
RESULTS
Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 - 0.96), OR = 0.73, (95%CI 0.61 - 0.86), and OR = 0.74, (95%CI 0.66 - 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 - 0.83)].
CONCLUSIONS
No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.
Topics: Humans; Stroke Volume; Sodium-Glucose Transporter 2 Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Heart Failure; Angiotensin-Converting Enzyme Inhibitors; Death
PubMed: 36348348
DOI: 10.1186/s12933-022-01679-2 -
Pharmaceutics Oct 2022Hypertension is a known risk factor for cognition-related pathologies including dementia. The National Institute of Health and Care Excellence (NICE) guidelines... (Review)
Review
Hypertension is a known risk factor for cognition-related pathologies including dementia. The National Institute of Health and Care Excellence (NICE) guidelines recommend angiotensin (Ang) II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) as a first-line treatment for hypertension. Although both ARBs and ACEIs show neuroprotective effects, ACEIs show contradictory side effects; therefore, ARBs may be a more viable option. However, trials assessing the effects of ARBs on cognition are scarce and conflicting. Therefore, the aim of this review is to conduct a systematic review and synthesise data on the influence of ARBs on cognition and dementia prevention. Five databases were searched from 1992-2022 to produce 13 randomised controlled trials (RCTs) involving 26,907 patients that compared associations of ARBs against placebos or other antihypertensives on cognition or probable dementia with a minimum duration of 3 months. ARBs showed greater cognitive benefits when compared to hydrochlorothiazide (HCTZ), beta blockers (BB), and ACEIs. Our findings showed that although ARBs are superior to some antihypertensives such as ACEIs, thiazide and beta blockers, they made no difference in comparison to the placebo in all but one sample of patients. The positive effects on cognitive performances are equal to calcium channel blockers (CCBs) and lower than statin. The neuroprotective effects of ARBs are also more beneficial when ARBs are taken at the same time as a statin. Due to these inconsistencies, robust conclusions cannot be made. Future trials are warranted and, if successful, could have positive economic implications and consequently improve quality of life.
PubMed: 36297558
DOI: 10.3390/pharmaceutics14102123 -
Medicine Oct 2022LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) has not been fully elucidated. This study aimed to provide the latest evidence regarding the efficacy and safety of LCZ696 as compared to other ACEis and ARBs with regards to the treatment of HF.
METHODS
We systematically searched databases, including PubMed, Embase, and the Cochrane Library, for relevant randomized controlled trials (RCTs). The outcome measures included all-cause mortality, rate of hospitalizations for HF, rate of death from cardiovascular causes, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and decline of renal function.
RESULTS
Five RCTs involving 19,078 patients were identified. The meta-analysis indicated that LCZ696 was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.76-0.93; P = .0005), rate of hospitalizations for HF (HR = 0.80; 95% CI, 0.73-0.87; P < .00001), reduction in NT-proBNP levels (rate ratio = 0.78; 95% CI, 0.70-0.88; P < .0001), and decline in renal function (odds ratio = 0.77; 95% CI, 0.68-0.88; P < .0001) compared with ACEis and ARBs. However, there was no statistical difference in the rate of death from cardiovascular causes (HR = 0.86; 95% CI, 0.72-1.03; P = .09) between LCZ696 and ACEis and ARBs.
CONCLUSION
LCZ696 is superior to ACEis and ARBs in the treatment of HF. Hence, it should be more widely used clinically.
Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Antihypertensive Agents; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Neprilysin; Randomized Controlled Trials as Topic; Receptors, Angiotensin; Valsartan
PubMed: 36254034
DOI: 10.1097/MD.0000000000030904 -
The Journal of Innovations in Cardiac... Sep 2022Angiotensin receptor-neprilysin inhibitor (ARNI) use has become increasingly popular. Current guidelines recommend using ARNI therapy for heart failure with reduced... (Review)
Review
Angiotensin receptor-neprilysin inhibitor (ARNI) use has become increasingly popular. Current guidelines recommend using ARNI therapy for heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). As therapies become more widely available, heart failure-associated burdens such as ventricular arrhythmias and sudden cardiac death (SCD) will become increasingly prevalent. We conducted a systematic review and meta-analysis to assess the impact of ARNI therapy on HFrEF and HFpEF pertaining to arrhythmogenesis and SCD. We performed a search of MEDLINE (PubMed), the Cochrane Library, and ClinicalTrials.gov for relevant studies. The odds ratios (ORs) of SCD, ventricular tachycardia (VT), ventricular fibrillation (VF), atrial fibrillation/flutter (AF), supraventricular tachycardia (SVT), and implantable cardioverter-defibrillator (ICD) shocks were calculated. A total of 10 studies, including 6 randomized controlled trials and 4 observational studies, were included in the analysis. A total of 18,548 patients from all studies were included, with 9,328 patients in the ARNI arm and 9,220 patients in the angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) arm, with a median follow-up time of 15 months. There was a significant reduction in the composite outcomes of SCD and ventricular arrhythmias in patients treated with ARNIs compared to those treated with ACEIs/ARBs (OR, 0.71; 95% confidence interval, 0.54-0.93; = .01; I = 17%; = .29). ARNI therapy was also associated with a significant reduction in ICD shocks. There was no significant reduction in the VT, VF, AF, or SVT incidence rate in the ARNI group compared to the ACEI/ARB group. In conclusion, the use of ARNIs confers a reduction in composite outcomes of SCD and ventricular arrhythmias among patients with heart failure. These outcomes were mainly driven by SCD reduction in patients treated with ARNIs.
PubMed: 36196235
DOI: 10.19102/icrm.2022.130905 -
Heart Failure Reviews Jul 2023Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety profile of angiotensin receptor neprilysin inhibitors in the management of heart failure: a systematic review and meta-analysis of randomized controlled trials.
Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the management of heart failure. Till date, there are no reviews done that comprehensively cover different aspects of efficacy and safety parameters. Hence, we have performed a comprehensive systematic review and meta-analysis on role of ARNIs for the management of heart failure patients. Searches were done in Embase, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, PubMed Central, Cochrane Library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov until June 2022. Risk of bias assessment was done with Cochrane's risk of bias tool. Meta-analysis was carried out using random-effects model. Pooled standardized mean difference (SMD)/mean difference (MD) and/or risk ratio (RR) with 95% confidence intervals (CIs) was reported. In total, we analysed 34 studies, with almost all of them had a high risk of bias. Pooled RR was 0.88 (95% CI: 0.82-0.95) for all-cause mortality, 0.84 (95% CI: 0.77-0.92) for cardiovascular mortality and 0.78 (95% CI: 0.70-0.87) for hospitalization. Pooled MD was 3.74 (95% CI: 1.93-5.55) for left ventricular ejection fraction, -2.16 (95% CI: -3.58 to -0.74) for left atrial volume index, -3.80 (95% CI: -6.60 to -1.00) for left ventricular end-diastolic dimension and -1.16 (95% CI: -1.98 to -0.35) for E/E' ratio. Regarding adverse events, pooled RR was 1.55 (95% CI: 1.31-1.85) for symptomatic hypotension, 0.93 (95% CI: 0.78-1.11) for worsening renal function, 1.09 (95% CI: 0.94-1.26) for hyperkalaemia and 1.29 (95% CI: 0.67-2.50) for angioedema. ARNIs had beneficial efficacy and safety profile on the management of heart failure especially patients with reduced ejection fraction.
Topics: Humans; Neprilysin; Stroke Volume; Ventricular Function, Left; Randomized Controlled Trials as Topic; Heart Failure; Angiotensin Receptor Antagonists
PubMed: 36184714
DOI: 10.1007/s10741-022-10273-3 -
Current Problems in Cardiology Jan 2023We conducted a systematic review and meta-analysis to assess all-cause mortality and heart failure (HF) hospitalization with sacubitril/valsartan (S/V) compared to... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis to assess all-cause mortality and heart failure (HF) hospitalization with sacubitril/valsartan (S/V) compared to standard HF therapy in patients with HF with reduced ejection fraction (HFrEF) using real-world data. We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and Google Scholar for the observational studies published in English exploring the clinical outcomes of S/V use in HFrEF till March 14, 2022. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The outcomes assessed were all-cause mortality and HF hospitalization associated with S/V use in comparison to standard HF therapy. A total of 9 observational studies comparing S/V to Angiotensin-converting enzyme inhibitors (ACE-I)/Angiotensin II receptor blockers (ARB) in HFrEF were included in the systematic review, with more than 32000 patients included in the final analysis. Overall, S/V use was associated with a significant reduction in all-cause mortality (Risk Ratio [RR] = 0.70, 95% CI 0.53-0.93, I = 83%) and HF hospitalization (RR = 0.62; 95% CI, 0.48-0.80, I= 94%). Similar to the landmark controlled evidence, real-world data of S/V use in HFrEF demonstrated a significant reduction in all-cause mortality and HF hospitalization.
Topics: Humans; Heart Failure; Angiotensin Receptor Antagonists; Stroke Volume; Tetrazoles; Angiotensin-Converting Enzyme Inhibitors; Valsartan; Ventricular Dysfunction, Left
PubMed: 36170910
DOI: 10.1016/j.cpcardiol.2022.101412 -
Clinical and Applied... 2022There is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events.
METHODS
A systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I statistic. Forest plots were created to show the pooled results of each outcome.
OUTCOMES
A total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: -0.81 mm/y, 95% CI: -1.19 to -0.42, P < 0.0001, I = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: -0.03 to 0.65, P = 0.07, I = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: -0.27 mm/y, 95% CI: -0.88 to 0.34, P = 0.39, I = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: -1.11mm/year, 95%CI: -2.38 to 0.16, P = 0.09, I = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I = 92%).
CONCLUSION
In conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.
Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Humans; Metformin; Propranolol
PubMed: 36083182
DOI: 10.1177/10760296221120423