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The Cochrane Database of Systematic... Oct 2018The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years,...
BACKGROUND
The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further.
OBJECTIVES
To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months.
SEARCH METHODS
On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies.
SELECTION CRITERIA
We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria.
MAIN RESULTS
We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).A multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to -2.2; placebo group median 2.2%, IQR 1.3 to -3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (-1.8%, IQR -2.9 to 6.0) than in the placebo group (-3.7%, IQR -10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).A randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).Some studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice.
AUTHORS' CONCLUSIONS
Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.
Topics: Adolescent; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Disease Progression; Eplerenone; Human Growth Hormone; Humans; Lisinopril; Losartan; Male; Muscular Dystrophy, Duchenne; Non-Randomized Controlled Trials as Topic; Perindopril; Placebos; Randomized Controlled Trials as Topic; Stroke Volume; Ubiquinone; Young Adult
PubMed: 30326162
DOI: 10.1002/14651858.CD009068.pub3 -
Mayo Clinic Proceedings Oct 2022To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).
METHODS
PubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.
RESULTS
Thirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, -0.54 [95% CI, -0.88 to -0.21]; P=.002; I=96%), IL-6 (WMD, -0.84 [95% CI, -1.03 to -0.64]; P<.001; I=0%), and TNF-α (WMD, -12.75 [95% CI, -17.20 to -8.29]; P<.001; I=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, -1.34 [95% CI, -2.65 to -0.04]; P=.04; I=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, -1.07 to -0.27]; P=.001; I=94%) and in patients with coronary artery disease (WMD, -0.75 [95% CI, -1.17 to -0.33]; P<.001; I=96%).
CONCLUSION
Based on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antihypertensive Agents; Biomarkers; C-Reactive Protein; Enalapril; Humans; Interleukin-6; Perindopril; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Tumor Necrosis Factor-alpha
PubMed: 36202494
DOI: 10.1016/j.mayocp.2022.06.036 -
Journal of Cellular Physiology May 2019The renin-angiotensin system (RAS) is an ever-evolving endocrine system with considerable checks and balances on the production and catabolism of angiotensin peptides... (Meta-Analysis)
Meta-Analysis
The renin-angiotensin system (RAS) is an ever-evolving endocrine system with considerable checks and balances on the production and catabolism of angiotensin peptides most likely due to the manifold effects of angiotensins. We aimed to explore the effects of different inhibitors of RAS on blood pressure and expression of inflammatory factors in patients with coronary heart disease (CHD). We initially searched PubMed, EMBASE and Cochrane Library electronic databases with nine eligible randomized controlled trials enrolled. Direct and indirect evidence was combined to calculate the weighted mean difference value and draw surface under the cumulative ranking curves. The results demonstrated that, compared with placebo and enalapril, ramipril had a better effect on reducing systolic blood pressure after short-term usage of drugs (<12 months), while perindopril had better effects on reducing diastolic blood pressure and C-reactive protein expression. Furthermore, after long-term usage of drugs (≥12 months), there was no significant difference among olmesartan, quinapril and candesartan in the treatment of patients with CHD. Perindopril and ramipril had better effects on inhibiting blood pressure and expression of inflammatory factors among eight inhibitors after short-term usage of drugs (<12 months); while quinapril had better effects on reducing blood pressure and expression of inflammatory factor after long-term usage of drugs, and there was little difference in the effects between olmesartan and candesartan (≥12 months). Perindopril may have better short-term effects on reducing blood pressure and expression of inflammatory factor, while quinapril may have better long-term effects on reducing blood pressure and expression of inflammatory factor.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antihypertensive Agents; Biomarkers; Blood Pressure; Coronary Disease; Humans; Inflammation Mediators; Network Meta-Analysis; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Time Factors; Treatment Outcome
PubMed: 30537058
DOI: 10.1002/jcp.27147 -
Heart Failure Reviews Mar 2018Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for... (Meta-Analysis)
Meta-Analysis
Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for mineralocorticoid antagonists (MRAs), β-adrenoceptor blockers (β-blockers), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs)-to reduce clinical outcomes in HFpEF remains unclear. We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov for randomized controlled trials (RCTs) assessing pharmacological treatments in HFpEF diagnosed according the recommendations of the European Society of Cardiology (ESC) 2016 guidelines from inception to August, 2017. The study outcomes were mortality, hospitalization, changes in indexes of cardiac structure and function, biomarkers, and indexes of functional capacity-quality of life (QoL) assessment and 6-min walk distance test (6-MWD). The random-effects models were used to estimate pooled relative risks (RRs) for the binary outcomes and standardized mean differences for continuous outcomes, with 95% CI. A network meta-analysis using a random-effects model was employed to estimate the comparative efficacy of treatments. We included data from 15 RCTs comprising 5930 patients. There was no significant effect seen with all treatments compared with placebo and comparative efficacy of any two treatments on all outcomes assessed. However, mineralocorticoid antagonist spironolactone demonstrated a trend towards reducing mortality compared with placebo (RR 0.92; 95% CI 0.79-1.08), sildenafil (0.14; 0.01-2.78), perindopril (0.87; 0.59-1.28), and eplerenone (0.91; 0.25-3.33). Similar trends in treatment effect were observed with spironolactone on surrogate outcomes while eplerenone demonstrated a trend of superior effect in reduction of hospitalizations compared with all other drug treatment. No drug treatment demonstrated statistically significant improvement in clinical and surrogate outcomes in HFpEF diagnosed according to the ESC 2016 guideline. Spironolactone and eplerenone showed clinically relevant reduction in mortality and hospitalization respectively compared with other drug treatments. Further trials with MRAs are warranted to confirm treatment effects in HFpEF.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Quality of Life; Stroke Volume
PubMed: 29411216
DOI: 10.1007/s10741-018-9679-y -
Pharmacological Research Jan 2020Although previous clinical randomized controlled trials (RCTs) have tested the effect of a variety of cardioprotective agents on cancer therapy-induced cardiotoxicity,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although previous clinical randomized controlled trials (RCTs) have tested the effect of a variety of cardioprotective agents on cancer therapy-induced cardiotoxicity, the number of included patients was limited, and the results remained controversial. In this study, we aimed to evaluate the preventive or therapeutic effects of cardioprotective agents on heart failure (HF) caused by cardiotoxicity induced by cancer therapy.
METHODS
We included trials of the following cardioprotective drugs: Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, aldosterone antagonists and stains. We extracted the relevant information with predefined data extraction forms, and assessed the risk of bias in randomized controlled trials with the Cochrane risk of bias tool. The primary outcome was the left ventricular ejection fraction of patients after chemotherapy. We used the random-effects model to carry out pair-wise meta-analysis, and then carry out the random-effects network meta-analysis within the Bayesian framework.
RESULTS
Twenty-two relevant RCTs, including 1 916 patients (79.6 % women) with a mean age of 48.4 years, were included. Based on the evaluation of all drug species from 20 studies (26 comparisons), the analysis found that 4 therapies, aldosterone antagonists (MD, 12.78 [95 % CI, 2.87-22.69] and MD, 13.75 [95 % CI, 2.21-25.30]), ACEIs (MD, 6.79 [95 % CI, 2.11-11.48] and MD, 7.76 [95 % CI, 2.64-12.88]), statin (MD, 8.35 [95 % CI, 1.11-15.59]), and beta-blockers (MD, 4.00 [95 % CI, 0.87-7.14]), had a higher efficacy than placebo and/or control, suggesting an LVEF protective effect of cardioprotective therapy. In the analysis classified by single drug or drug combination, based on 22 studies (31 comparisons), spironolactone (MD, 12.77 [95 % CI, 1.76-23.79] and MD, 14.62 [95 % CI, 1.70-27.55]), a combination of candesartan and carvedilol (MD, 12.40 [95 % CI, 0.99-23.81]), enalapril (MD, 7.35 [95 % CI, 1.16-13.54] and MD, 9.20 [95 % CI, 2.61-15.79]), and statin (MD, 8.36 [95 % CI, 0.36-16.36]) showed significant benefits in protecting left ventricular (LV) systolic function compared with the placebo and/or control.
CONCLUSION
When classified according to drug type, aldosterone antagonists, ACEIs, statins, and beta-blockers could substantially improve the LV systolic function. In the analysis classified by single drug or drug combination, spironolactone, enalapril, and statin have a significant cardioprotective effect. However, ARBs have no cardioprotective effect and fail to improve the LVEF.
Topics: Antineoplastic Agents; Cardiotonic Agents; Heart; Heart Failure; Humans; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 31790821
DOI: 10.1016/j.phrs.2019.104577 -
Current Pain and Headache Reports Sep 2019Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with...
PURPOSE OF REVIEW
Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with migraine. To identify gaps in research and provide guidance for future clinical trials.
RECENT FINDINGS
A search was completed using PubMed, MEDLINE, Embase, and the Cochrane Library January 1, 1990 through December 31, 2017. The following are keywords used in the search: migraine, migraine prophylaxis/prevention, renin-angiotensin-aldosterone system, RAAS, ACE inhibitors, angiotensin-converting enzyme inhibitors: quinapril, perindopril, ramipril, captopril, enalapril, lisinopril, benazepril, fosinopril. Angiotensin receptor blockers, ARB, angiotensin II receptor antagonists: candesartan cilexetil, irbesartan, olmesartan, valsartan, losartan, azilsartan medoxomil, telmisartan, and eprosartan. The search included randomized controlled trials (RCT), systemic reviews and open-label studies of ACE inhibitors and ARB for the prevention of migraine attacks in adults 18-70 years old. Of 2461 retrieved articles, 18 included RCT, meta-analysis, systemic reviews, or guidelines published on ACE inhibitors or ARB in the prevention of migraine. Three RCT with telmisartan 80 mg, candesartan 16 mg, and enalapril 10 mg, and two open-label trials with lisinopril 5 mg and ramipril 5 mg found a high number of responders with greater than 50 % reduction in migraine attack frequency when compared to a 4-week baseline period. Candesartan was superior to placebo while telmisartan and enalapril were not. Lipophilic ACE inhibitors and ARBs can be effective prophylactic agents for reduction of migraine frequency in adults. Based on the limited number of published trials and small sample size, they are not recommended as first-line prophylactic agents. However, in populations with co-morbidities such as hypertension, they may be useful as first- or second-line prophylactics. Additional trials following the International Headache Society's guidelines on RCT are warranted.
Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Male; Migraine Disorders
PubMed: 31515634
DOI: 10.1007/s11916-019-0823-8 -
Frontiers in Pharmacology 2024[This corrects the article DOI: 10.3389/fphar.2023.1156655.].
[This corrects the article DOI: 10.3389/fphar.2023.1156655.].
PubMed: 38903988
DOI: 10.3389/fphar.2024.1426608