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Heart, Lung & Circulation Mar 2024Chronic kidney disease (CKD) coexists in up to 50% of heart failure (HF) patients, affecting both those with reduced ejection fraction (HFrEF) and those with preserved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic kidney disease (CKD) coexists in up to 50% of heart failure (HF) patients, affecting both those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF). Although the efficacy of several guideline-directed medical therapies (GDMT) has been well established, the treatment recommendations are similar for those patients with HF with and without CKD. We aimed to investigate the efficacy of GDMT in patients with HF with versus those without CKD.
METHOD
This systematic review and meta-analysis included randomised controlled trials that compared the efficacy of GDMT (angiotensin-converting enzyme inhibitor [ACE-I], beta blocker, sodium-glucose cotransporter-2 inhibitor, mineralocorticoid receptor antagonist, angiotensin receptor-neprilysin inhibitor) in patients with HF with and without CKD. The primary outcome was the composite of cardiovascular death and HF hospitalisation. Risk ratios (RR) were pooled using random-effects meta-analysis.
RESULTS
A total of 19 trials (15 trials in HFrEF and four trials in HFpEF) enrolling 63,677 (38% had CKD) participants were included. Among HFrEF patients, GDMT reduced the primary endpoint in those with CKD (RR 0.77, 95% confidence interval [CI] 0.72-0.82) and without CKD (RR 0.79, 95% CI 0.74-0.84). Among HFpEF patients, the pooled summary RR for GDMT reducing the primary endpoint was 0.82 (95% CI 0.74-0.91) among those with CKD and 0.88 (95% CI 0.77-0.99) among those without CKD. There was no significant difference in the efficacy of GDMT in head-to-head comparisons between those with and without CKD in HFrEF (ratio of RR 0.97, 95% CI 0.88-1.06) and HFpEF (ratio of RR 0.94, 95% CI 0.80-1.11).
CONCLUSIONS
Among patients with HF, GDMT had a consistent effect in reducing adverse cardiovascular events in those with and without CKD. Future studies should investigate the best strategy to ensure patients with HF with CKD receive and tolerate GDMT when indicated.
Topics: Humans; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume
PubMed: 38365495
DOI: 10.1016/j.hlc.2023.12.013 -
The Cochrane Database of Systematic... Feb 2024Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011.
OBJECTIVES
To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension.
SEARCH METHODS
We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension.
DATA COLLECTION AND ANALYSIS
Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis.
MAIN RESULTS
We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and β-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain.
AUTHORS' CONCLUSIONS
Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.
Topics: Humans; Antihypertensive Agents; Hypertension; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Essential Hypertension
PubMed: 38353289
DOI: 10.1002/14651858.CD004184.pub3 -
ESC Heart Failure Jun 2024Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by...
AIMS
Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by vaccination.
METHODS AND RESULTS
We did a systematic review, searching PubMed, Embase, Web of Science, Ovid MEDLINE, Journals@Ovid, and Scopus databases up to 26 April 2023 to identify case reports or case series of vaccine-induced TTS. We then extracted and summarized the data from these reports. Eighteen reports were identified, with a total of 19 patients with TTS associated with vaccinations. Of the 19 included patients, the majority were female (n = 13, 68.4%) with a mean age of 56.6 ± 21.9 years. Seventeen patients developed TTS after coronavirus disease 2019 vaccination, 14 of whom received an mRNA vaccination. Two cases of TTS occurred after influenza vaccination. Among the 19 patients, 17 (89.5%) completed transthoracic echocardiography and 16 (84.2%) underwent angiography procedures. Seven patients (36.8%) completed cardiac magnetic resonance imaging. The median time to symptom onset was 2 (inter-quartile range, 1-4) days. The most common symptoms were chest pain (68.4%), dyspnoea (57.9%), and digestive symptoms (31.6%). A total of 57.9% of patients developed nonspecific symptoms such as fatigue, myalgia, diaphoresis, and fever. Among the 16 reported cases of TTS, 15 patients (93.8%) exhibited elevated cardiac troponin levels, while among the nine reported cases, eight patients (88.9%) had elevated natriuretic peptide levels. All patients had electrocardiographic changes: ST-segment change (47.1%), T-wave inversion (58.8%), and prolonged corrected QT interval (35.3%). The most common TTS type was apical ballooning (88.2%). Treatment during hospitalization typically included beta-blockers (44.4%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (33.3%), and diuretics (22.2%). After treatment, 81.3% of patients were discharged with improved symptoms. Among this group, nine patients (56.3%) were reported to have recovered ventricular wall motion during follow-up. Two patients (12.5%) died following vaccination without resuscitation attempts.
CONCLUSIONS
TTS is a rare but potentially life-threatening complication of vaccination. Typical TTS symptoms such as chest pain and dyspnoea should be considered alarming symptoms, though nonspecific symptoms are common. The risks of such rare adverse events should be balanced against the risks of infection.
Topics: Humans; Takotsubo Cardiomyopathy; COVID-19 Vaccines; COVID-19; Vaccination; SARS-CoV-2; Echocardiography
PubMed: 38344896
DOI: 10.1002/ehf2.14719 -
Frontiers in Cardiovascular Medicine 2024There is controversy in relation to commonly used drugs in heart failure (HF) and their impact on muscle function. The aim of this study was to evaluate the odds of... (Review)
Review
BACKGROUND
There is controversy in relation to commonly used drugs in heart failure (HF) and their impact on muscle function. The aim of this study was to evaluate the odds of receiving specific medications often used in clinical practice by patients with HF and sarcopenia vs. without sarcopenia.
METHODS
A systematic literature search of cohort studies via databases (PubMed, Web of Science, Scopus, and Cochrane Library) was conducted from inception until March 2023. To determine if sarcopenia is linked to a higher number of specific HF-related medications, a meta-analysis using a random-effects model was used to calculate the pooled effects.
RESULTS
Our main analyses showed no significant association of sarcopenia with administration of higher HF-related medication count vs. those without sarcopenia. Those with lower appendicular lean mass (ALM) had significantly lower odds of receiving angiotensin converting enzyme inhibitors (ACE-Is)/angiotensin receptor blockers (ARBs) (OR: 0.68, 95%CI 0.50-0.90, = 12%, < 0.01) vs. patients with higher ALM for which age could be an important confounder based on meta-regression. No statistically significant differences were found in relation to B-blockers OR: 0.84, 95%CI 0.63-1.12, = 7%, = 0.24) and loop diuretics (OR: 1.19, 95%CI 0.87-1.63, = 0%, = 0.27). Regarding handgrip strength, gait speed, and short physical performance battery, our narrative synthesis found mixed results.
CONCLUSION
This systematic review and meta-analysis did not find a relationship of specific medication count in sarcopenia vs. without sarcopenia in patients with HF, although increased odds of ACE-I/ARB was shown in those with higher ALM.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42023411137).
PubMed: 38333416
DOI: 10.3389/fcvm.2024.1293537 -
Annals of Medicine and Surgery (2012) Feb 2024Hypertension has significantly contributed to morbidity and mortality, necessitating effective management. Angiotensin receptor blockers (ARBs) have emerged as a... (Review)
Review
BACKGROUND
Hypertension has significantly contributed to morbidity and mortality, necessitating effective management. Angiotensin receptor blockers (ARBs) have emerged as a cornerstone in hypertension treatment. Azilsartan, a relatively recent addition to the ARB family, offers unique characteristics, including prodrug activation. This systematic review and meta-analysis aimed to evaluate Azilsartan's role in reducing clinical blood pressure compared to other ARBs and determine the most effective dosage.
METHODS
Following PRISMA guidelines, a comprehensive literature search was conducted in Medline, Web of Science, Cochrane Library, and clinicaltrials.gov. Eligible studies included adult hypertensive patients receiving Azilsartan compared to other ARBs, with clinical systolic blood pressure (SBP) and diastolic blood pressure (DBP) outcomes. Data extraction and quality assessment were performed, and statistical analysis employed comprehensive meta-analysis (CMA) software.
RESULTS
Eleven randomized controlled trials encompassing 18 studies involving 6024 patients were included. Azilsartan demonstrated significant reductions in clinical SBP (mean difference=-2.85 mmHg) and DBP (mean difference=-2.095 mmHg) compared to other ARBs. Higher doses of Azilsartan showed greater efficacy, with 80 mg exhibiting the most substantial reduction in SBP. The analysis emphasized the need for more studies investigating lower Azilsartan doses (10 and 20 mg).
CONCLUSION
This systematic review and meta-analysis underscore Azilsartan's effectiveness in reducing SBP and DBP. Dose-dependent effects emphasize the importance of optimal dosing when prescribing Azilsartan. These findings provide valuable insights for clinicians in managing hypertension effectively and call for further research, primarily focusing on lower Azilsartan doses and a more diverse patient population.
PubMed: 38333313
DOI: 10.1097/MS9.0000000000001547 -
The Cochrane Database of Systematic... Feb 2024IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011.
OBJECTIVES
To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events.
AUTHORS' CONCLUSIONS
Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.
Topics: Humans; Antihypertensive Agents; East Asian People; Glomerulonephritis, IGA; Hematuria; Proteinuria; Recurrence; Renal Insufficiency
PubMed: 38299639
DOI: 10.1002/14651858.CD003962.pub3 -
Drug Safety May 2024Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug...
BACKGROUND
Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.
PURPOSE
The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.
DATA SOURCES
The PubMed and EMBASE databases were searched up to November, 1st 2023.
STUDY SELECTION
We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.
DATA EXTRACTION
Two authors independently extracted the data.
DATA SYNTHESIS
Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced C and delayed t of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.
LIMITATIONS
The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).
CONCLUSIONS
To conclude, reduced C and delayed t of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Interactions; Glucagon-Like Peptide 1; Warfarin
PubMed: 38273155
DOI: 10.1007/s40264-023-01392-3 -
International Journal of Cardiology Apr 2024Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with heart failure reduced ejection fraction (HFrEF). This study aimed to assess the relative efficacy of vericiguat and sacubitril/valsartan through a systematic review, network meta-analysis, and non-inferiority tests.
METHODS
A systematic review was conducted to identify the randomized phase 3 clinical trials involving vericiguat and sacubitril/valsartan. The hazard ratios (HRs) with 95% confidence intervals (CI) for cardiovascular death (CVD) and hospitalization due to HF (hHF) were extracted from these trials and synthesized via network meta-analysis. Non-inferiority testing of vericiguat was performed using a fixed-margin method with a predefined non-inferiority margin (1.24). Sensitivity analyses explored the impact of the time from hHF to screening.
RESULTS
Among the 1366 studies, two trials (VICTORIA and PARADIGM-HF) met the inclusion criteria. Network meta-analysis demonstrated that the HR for CVD or hHF with vericiguat did not significantly differ from that for sacubitril/valsartan (HR: 0.88, 95% CI:0.62-1.23). The upper limit of the 95% CI was less than the predefined margin of 1.24, confirming vericiguat's non-inferiority to sacubitril/valsartan. Sensitivity analyses affirmed the robustness of the base-case results.
CONCLUSION
Vericiguat exhibited a comparable risk of CVD or hHF when contrasted with sacubitril/valsartan. Importantly, in patients with HFrEF, vericiguat's efficacy was not statistically inferior to that of sacubitril/valsartan. These findings reinforce the potential of vericiguat as a viable treatment option for this patient population.
Topics: Humans; Heart Failure; Network Meta-Analysis; Tetrazoles; Stroke Volume; Valsartan; Aminobutyrates; Biphenyl Compounds; Drug Combinations; Ventricular Dysfunction, Left; Angiotensin Receptor Antagonists; Heterocyclic Compounds, 2-Ring; Pyrimidines
PubMed: 38242507
DOI: 10.1016/j.ijcard.2024.131786 -
Journal of Hypertension May 2024Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits and harms of blood pressure lowering agents in people with a functioning kidney transplant.
METHODS
We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, and CENTRAL through to October 2023. RCTs evaluating blood pressure lowering agents administered for at least 2 weeks in people with a functioning kidney transplant with and without preexisting hypertension were eligible. Two reviewers independently extracted data. The primary outcome was graft loss. Treatment effects were estimated using random effects network meta-analysis, with treatment effects expressed as an odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes together with their 95% confidence interval (CI). Confidence in the evidence was assessed using GRADE for network meta-analysis.
RESULTS
Ninety-four studies (7547 adults) were included. Two studies were conducted in children. No blood pressure-lowering agent reduced the risk of graft loss, withdrawal because of adverse events, death, cardiovascular or kidney outcomes compared with placebo/other drug class. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker therapy may incur greater odds of hyperkalemia compared with calcium channel blockers [odds ratio (OR) 5.48, 95% confidence interval (CI) 2.47-12.16; and OR 8.67, 95% CI 2.65-28.36; low certainty evidence, respectively).
CONCLUSION
The evidentiary basis for the comparative benefits and safety of blood pressure lowering agents in people with a functioning kidney transplant is limited to guide treatment decision-making.
Topics: Child; Adult; Humans; Blood Pressure; Kidney Transplantation; Network Meta-Analysis; Hypertension; Angiotensin-Converting Enzyme Inhibitors
PubMed: 38230619
DOI: 10.1097/HJH.0000000000003663 -
Journal of Human Hypertension May 2024Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not... (Meta-Analysis)
Meta-Analysis
Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by -6.8 mmHg (95% confidence interval -9.6 to -4.1) and -4.8 mmHg (95% confidence interval -11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Hypertension; Treatment Outcome; Renin; Blood Pressure; Antihypertensive Agents
PubMed: 38200100
DOI: 10.1038/s41371-023-00891-1