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Diabetes, Obesity & Metabolism Nov 2022To compare the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (MRAs), selective aldosterone... (Meta-Analysis)
Meta-Analysis
Effects of sodium-glucose cotransporter-2 inhibitors and aldosterone antagonists, in addition to renin-angiotensin system antagonists, on major adverse kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A systematic review and network meta-analysis.
AIMS
To compare the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (MRAs), selective aldosterone antagonists and nonselective aldosterone antagonists, on top of renin-angiotensin-aldosterone system (RAAS) blockade, in reducing kidney-specific composite events, cardiovascular outcomes, and other events of special interest in participants with type 2 diabetes (T2D) and chronic kidney disease (CKD).
METHODS
PubMed, EMBASE and CENTRAL were searched for studies published up to January 20, 2022. Randomized clinical trials enrolling participants with T2D and CKD were included, in which SGLT2 inhibitors, nonsteroidal MRAs, selective aldosterone antagonists and nonselective aldosterone antagonists were compared with either each other, or with placebo or no treatment. A network meta-analysis using a Bayesian approach was performed. The primary outcome was a kidney-specific composite event. Secondary outcomes included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and all-cause mortality. We also examined blood pressure and safety outcomes of interest, including acute kidney injury, hyperkalaemia, hyponatraemia, and volume reduction events. All research was conducted according to a protocol registered in the PROSPERO database (CRD42022307113).
RESULTS
This meta-analysis of 17 trials randomizing 22 981 participants found SGLT2 inhibitors (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52 to 0.73) and nonsteroidal MRAs (OR 0.76, 95% CI 0.66 to 0.88) were associated with significantly lower kidney-specific composite events than the control groups. Nonsteroidal MRAs (OR 0.78, 95% CI 0.66 to 0.92) and SGLT2 inhibitors (OR 0.57, 95% CI 0.45 to 0.72) were associated with greater reductions in hospitalization for heart failure than the control groups. SGLT2 inhibitors were associated with a lower risk of hospitalization for heart failure events compared with nonsteroidal MRAs (OR 0.73, 95% CI 0.55-0.97). SGLT2 inhibitors were associated with a reduction in cardiovascular death (OR 0.80, 95% CI 0.65 to 0.98) and all-cause mortality (OR 0.79, 95% CI 0.66 to 0.93) compared with the control groups. When compared to the control groups, both nonsteroidal MRAs (weighted mean difference [WMD] -10.96, 95% CI -20.49 to -1.46) and SGLT2 inhibitors (WMD -3.50, 95% CI -6.01 to -1.013) were linked with lower systolic blood pressure, nonsteroidal MRAs (OR 2.27, 95% CI 2.02 to 2.56) and nonselective aldosterone antagonists (OR 3.22, 95% CI 1.43 to 7.66) were associated with an increased risk of hyperkalaemia, nonsteroidal MRAs were linked with an increased risk of hyponatraemia (OR 16.56, 95% CI 2.78 to 455.19), and SGLT2 inhibitors were associated with an increased risk of volume reduction events (OR 1.28, 95% CI 1.06 to 1.56). SGLT2 inhibitors were ranked the best for our primary and secondary outcomes. Confidence in the evidence was often high or moderate.
CONCLUSIONS
In this network meta-analysis, the use of SGLT2 inhibitors or nonsteroidal MRAs, combined with RAAS blockade, was associated with a reduction in kidney-specific composite events and hospitalization for heart failure events in patients with T2D and CKD compared to placebo or no treatment. SGLT2 inhibitors were associated with a lower risk of hospitalization for heart failure events compared with nonsteroidal MRAs. Use of SGLT2 inhibitors was associated with lower mortality than placebo or no treatment.
Topics: Bayes Theorem; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Hyperkalemia; Hyponatremia; Kidney; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35712807
DOI: 10.1111/dom.14801 -
Journal of Hypertension Jun 2022Obstructive sleep apnoea (OSA) is a common cause of secondary hypertension. This network meta-analysis (NMA) assessed the effect of different OSA treatments on lowering... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Obstructive sleep apnoea (OSA) is a common cause of secondary hypertension. This network meta-analysis (NMA) assessed the effect of different OSA treatments on lowering blood pressure.
METHODS
PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for relevant randomized controlled trials. The search strategies included the concepts of OSA, blood pressure, hypertension, and blood pressure-reducing treatments without language or data restriction (from inception to 1 June 2021). The outcomes included office SBP, office DBP, daytime SBP (dSBP) and DBP (dDBP), and night-time SBP (nSBP) and DBP (nDBP). A Bayesian network meta-analysis was performed, and mean differences with 95% credibility intervals were calculated.
RESULTS
We reviewed 49 randomized controlled trials involving 4893 patients and the following interventions: continuous positive-airway pressure (CPAP), mandibular advancement devices, nocturnal supplemental oxygen, surgery, β-blocker, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), renal sympathetic denervation (RDN), mineralocorticoid receptor antagonists (MRAs), calcium channel blockers. MRAs were significantly associated with blood pressure reduction followed by ACEI/ARB. RDN could reduce office SBP, office DBP, 24-h SBP, 24-h DBP, dSBP, and dDBP. CPAP also demonstrated modest blood pressure lowering.
CONCLUSION
MRAs and ACEIs/ARBs can reduce blood pressure effectively in patients with OSA. RDN is a novel hypertension treatment that lowered blood pressure in such patients. CPAP was associated with mild but stable blood pressure reduction, and it might be helpful as an adjunctive therapy in OSA patients with hypertension.
REVIEW REGISTRATION
This systematic review and meta-analysis was registered in PROSPERO: CRD42021240891.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bayes Theorem; Blood Pressure; Continuous Positive Airway Pressure; Humans; Hypertension; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive
PubMed: 35703874
DOI: 10.1097/HJH.0000000000003131 -
International Journal of Retina and... Jun 2022Mineralocorticoid receptor antagonists (MRAs) are widely used for chronic central serous chorioretinopathy (cCSCR), but their effectiveness remains unclear. This...
BACKGROUND
Mineralocorticoid receptor antagonists (MRAs) are widely used for chronic central serous chorioretinopathy (cCSCR), but their effectiveness remains unclear. This research was conducted to evaluate the efficacy of this drugs for cCSCR.
METHODS
This is a review of randomized clinical trials (RCT) comparing MRAs to placebo in adults with cCSCR, using the effects of MRAs on best-corrected visual acuity (BCVA) and adverse events as primary outcomes and the effects of MRAs on anatomical parameters as secondary outcomes: central subfield thickness (CST), subretinal fluid height (SFH) and central choroidal thickness (CCT). Our all-language online search included Medline (via PubMed), Central, Embase, Lilacs, Ibecs, and RCT registers platforms, as late as May 2021. We used the Cochrane risk-of-bias tool (version 2) to assess the methodological quality of each study and synthesized the results in meta-analyses using a random-effects model.
RESULTS
The search identified 302 records, five of which were eligible, totaling 225 cCSCR patients (aged 45-62 years; M/F ratio 3.1:1) treated for 1 to 12 months with spironolactone (50 mg/day) or eplerenone (50 mg/day) vs. placebo. Moderate-certainty evidence suggests MRAs result in little to no improvement in BCVA compared to placebo (SMD 0.22; 95% CI - 0.04 to 0.48; studies = 5; comparisons = 6; participants = 218; I = 0%). Very low-certainty evidence suggests that, when compared to placebo, MRAs have a very uncertain impact on adverse effects (no meta-analysis was performed), and CST (MD 18.1; 95% CI - 113.04 to 76.84; participants = 145; studies = 2; I = 68%). MRAs also result in little to no difference in SFH (SMD - 0.35; 95% CI - 0.95 to 0.26; studies = 5; comparisons = 6; participants = 221; I = 76%; moderate certainty) and CCT (MD - 21.23; 95% CI - 64.69 to 22.24; participants = 206; studies = 4; comparisons = 5; I = 85%; low certainty).
CONCLUSION
MRAs have little to no effect on BCVA. Evidence for adverse events and CST is very uncertain. MRAs also have little to no effect on SFH and CCT. These findings should be considered when prescribing MRAs for cCSCR. This research was previous registration in the PROSPERO platform (CRD42020182601).
PubMed: 35672807
DOI: 10.1186/s40942-022-00385-1 -
Frontiers in Pharmacology 2022Whether Mineralocorticoid receptor antagonists (MRA) reduce mortality and cardiovascular effects of dialysis patients remains unclear. A meta-analysis was designed to...
Whether Mineralocorticoid receptor antagonists (MRA) reduce mortality and cardiovascular effects of dialysis patients remains unclear. A meta-analysis was designed to investigate whether MRA reduce mortality and cardiovascular effects of dialysis patients, with a registration in INPLASY (INPLASY2020120143). The meta-analysis revealed that MRA significantly reduced all-cause mortality (ACM) and cardiovascular mortality (CVM). Patients receiving MRA presented improved left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF), decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP). There was no significant difference in the serum potassium level between the MRA group and the placebo group. MRA vs. control exerts definite survival and cardiovascular benefits in dialysis patients, including reducing all-cause mortality and cardiovascular mortality, LVMI, and arterial blood pressure, and improving LVEF. In terms of safety, MRA did not increase serum potassium levels for dialysis patients with safety. (https://inplasy.com/inplasy-protocol-1239-2/), identifier (INPLASY2020120143).
PubMed: 35656294
DOI: 10.3389/fphar.2022.823530 -
ESC Heart Failure Aug 2022Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
AIMS
Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments.
METHODS AND RESULTS
Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990-2021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 ± 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 ± 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75-0.99) in men; HR 0.97 (0.77-1.23) in women; P = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59-0.86) in men; HR 0.87 (0.73-1.03) in women; P = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77-0.93) in men; HR 0.94 (0.81-1.08) in women; P = 0.210] or BB [HR 0.76 (0.64-0.90) in men; HR 0.72 (0.60-0.86) in women; P = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (P = 0.78) or SGLT2i (P = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women.
CONCLUSIONS
Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women.
Topics: Female; Humans; Male; Middle Aged; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Mineralocorticoid Receptor Antagonists; Sex Characteristics; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left
PubMed: 35603531
DOI: 10.1002/ehf2.13974 -
European Journal of Cancer (Oxford,... Jul 2022Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown.
METHODS
Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI).
RESULTS
Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%).
CONCLUSION
Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bayes Theorem; Cardiotoxicity; Dexrazoxane; Female; Heart Failure; Humans; Hypotension; Male; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Stroke Volume; Ventricular Function, Left
PubMed: 35524992
DOI: 10.1016/j.ejca.2022.03.024 -
Hellenic Journal of Cardiology : HJC =... 2022The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients... (Meta-Analysis)
Meta-Analysis Review
The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients receiving guideline-directed treatment to identify the proportion of under-treatment patients and those who are treated with optimal doses, to evaluate the correlation of under-treatment patients' characteristics with the prescribed therapy, and finally, to evaluate the combined effect of the above on incidental mortality and rehospitalization. We conducted a systematic review of the literature indexed in Medline. We screened 1224 papers and excluded 1166 as they did not meet the inclusion criteria. Of the remaining 58 papers, which were evaluated by studying the full text, 11 papers that referred to 45866 patients were finally studied in this work. Angiotensin-Converting-Enzyme Inhibitor (ACEI) and Angiotensin II-Receptor Blocker (ARB) use was estimated to be 80.9% (95% CI: 73.9%, 86.4%), β-blockers' use was 78% (95% CI: 70.4%, 84.1%), Mineralocorticoid Receptor Antagonists' use was 47.4% (95% Cl 41.6%, 53.4%), and cardiac resynchronization therapy's use was 5.8% (95% Cl 3.4%, 9.6%). Meta-regression analysis showed that prescription of more than the half of target dose of ACEI/ARBs was found to be associated with reduced all-cause mortality (Z = -3.61, P = 0.0003), while the relationship with β-blockers was borderline (Z = -1.56, P = 0.11). A satisfactory adherence to the prescription of guideline-recommended treatment in patients with HF was observed. However, the under titration of the life-saving HF drugs need to be improved as only ultimate adherence to guideline-directed treatments may lead to the reduction of HF burden.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Stroke Volume
PubMed: 35508296
DOI: 10.1016/j.hjc.2022.04.006 -
Healthcare (Basel, Switzerland) Mar 2022Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been... (Review)
Review
Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been proposed. The protective effects of mineralocorticoid receptor antagonists (MRA) against tissue fibrosis, pulmonary and systemic vasoconstriction, and inflammation have been implicated in potentially attenuating the severity of SARS-CoV-2 infection by inhibiting the deleterious effects of aldosterone. Furthermore, spironolactone, a type of MRA, has been suggested to have a beneficial effect on SARS-CoV-2 outcomes through its dual action as an MRA and antiandrogen, resulting in reduced transmembrane protease receptor serine type 2 (TMPRSS2)-related viral entry to host cells. In this study, we sought to investigate the association between MRA antagonist therapy and mortality in SARS-CoV-2 patients via systematic review and meta-analysis. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE databases were searched for studies that reported the incidence of mortality in patients on MRA with SARS-CoV-2 infection. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using the random-effects model. Five studies with a total of 1,388,178 subjects (80,903 subjects receiving MRA therapy) met the inclusion criteria. We included studies with all types of MRA therapy including spironolactone and canrenone and found no association between MRA therapy and mortality in SARS-CoV-2 infection (OR = 0.387, 95% CI: 0.134-1.117, = 0.079).
PubMed: 35455823
DOI: 10.3390/healthcare10040645 -
Frontiers in Endocrinology 202211-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide...
BACKGROUND AND OBJECTIVES
11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.
DESIGN AND METHODS
We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.
RESULTS
We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.
CONCLUSIONS
11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.
SYSTEMATIC REVIEW REGISTRATION
Open Science Framework, 10.17605/OSF.IO/NR7UV.
Topics: Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adult; Aldosterone; Carcinoma; Desoxycorticosterone; Female; Humans; Hyperplasia; Hypertension; Male; Middle Aged
PubMed: 35432204
DOI: 10.3389/fendo.2022.846865 -
The American Journal of Managed Care Mar 2022To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart...
OBJECTIVES
To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF).
STUDY DESIGN
Systematic literature review.
METHODS
A systematic literature review was conducted in PubMed, Ovid MEDLINE, and Clinical Key covering January 1990 to December 2018. Key search terms were ADEs for β-blockers (BBs), ACE inhibitors (ACEis), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and/or angiotensin receptor-neprilysin inhibitors (ARNis) in adult patients (≥ 18 years) with HFrEF.
RESULTS
A total of 279 eligible articles were identified, of which 29 reported drug-related adverse effects and were included in this review. Of the 29 studies, 11 examined BBs; 9, MRAs; 6, ARNis; 2, ACEis; and 1, ARBs. The most common reported ADEs across these therapeutic classes included bradycardia, dizziness, hypotension, hyperkalemia, cough, and renal impairment. The incidence of BB-induced bradycardia was 1% to 52% based on 9 studies, and 6 studies described dizziness as a result of BBs and ARNis (15%-43%). Fourteen studies reported induced hypotension (1.4%-63%); 13 studies, hyperkalemia (0.6%-30.2%); 3 studies, cough (37%-50%); and 4 studies, renal impairment (0.6%-7.6%).
CONCLUSIONS
Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted.
Topics: Adrenergic beta-Antagonists; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bradycardia; Cough; Dizziness; Drug-Related Side Effects and Adverse Reactions; Heart Failure; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Stroke Volume
PubMed: 35404555
DOI: 10.37765/ajmc.2022.88844