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European Heart Journal. Cardiovascular... Jan 2024Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Randomized controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials.
METHODS
PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March-12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled.
RESULTS
Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66-1.41], ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72).
CONCLUSION
ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients.PROSPERO registration number: CRD42023408926.
Topics: Adult; Humans; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; COVID-19; Randomized Controlled Trials as Topic; Renin-Angiotensin System
PubMed: 37740450
DOI: 10.1093/ehjcvp/pvad067 -
Frontiers in Pharmacology 2023Stroke survivors are at significantly increased risk of cognitive impairment, which affects patients' independence of activities of daily living (ADLs), social...
Stroke survivors are at significantly increased risk of cognitive impairment, which affects patients' independence of activities of daily living (ADLs), social engagement, and neurological function deficit. Many studies have been done to evaluate the efficacy and safety of post-stroke cognitive impairment (PSCI) treatment, and due to the largely inconsistent clinical data, there is a need to summarize and analyze the published clinical research data in this area. An umbrella review was performed to evaluate the efficacy and safety of PSCI therapies. Three independent authors searched for meta-analyses and systematic reviews on PubMed, the Cochrane Library, and the Web of Science to address this issue. We examined ADL and Barthel index (BI), Montreal Cognitive Assessment (MoCA), neurological function deficit as efficacy endpoints, and the incidence of adverse events as safety profiles. In all, 312 studies from 19 eligible publications were included in the umbrella review. The results showed that angiotensin-converting enzyme inhibitors (ACEI) and N-methyl-D-aspartate (NMDA) antagonists, cell therapies, acupuncture, and EGB76 can improve the MoCA and ADL, and the adverse effects were mild for the treatment of PSCI. Moreover, Vinpocetine, Oxiracetam, Citicoline, thrombolytic therapy, Actovegin, DL-3-n-Butylphthalide, and Nimodipine showed adverse events or low article quality in patients with PSCI. However, the research evidence is not exact and further research is needed. Our study demonstrated that ACEI inhibitors (Donepezil) and NMDA antagonists (Memantine), EGB761, and acupuncture are the ADL and BI, MoCA, and neurological function deficit medication/therapy, respectively, for patients with PSCI. https://inplasy.com/inplasy-2022-11-0139/; Identifier: INPLASY2022110139.
PubMed: 37693907
DOI: 10.3389/fphar.2023.1207075 -
Seminars in Arthritis and Rheumatism Dec 2023The pathogenesis of scleroderma renal crisis (SRC) remains poorly understood but a growing body of evidence suggests that activation of the complement system may be... (Review)
Review
BACKGROUND
The pathogenesis of scleroderma renal crisis (SRC) remains poorly understood but a growing body of evidence suggests that activation of the complement system may be involved in the disease. Recent studies have shown that Eculizumab (monoclonal antibody directed against the complement component C5) is effective in treating patients with SRC who present with symptoms of thrombotic microangiopathy (SRC-TMA).
OBJECTIVES
In this study, we conducted a systematic review to characterize the published experience of the presentation and outcome of patients with SRC who were treated with C5 inhibitor, Eculizumab.
METHODS
A literature search was conducted from inception to December 2022 using Medical Subject Headings (MeSH) terms for 'scleroderma', 'scleroderma renal crisis, and 'Eculizumab'. We included case reports, case series, and observational studies which reported the use of Eculizumab with or without Angiotensin-converting enzyme inhibitors (ACE-I) for the treatment of scleroderma renal crisis (SRC) in patients with systemic sclerosis.
RESULTS
The study included 17 patients, all of whom were treated with Eculizumab. Additionally, the use of ACE-I was reported in 11/17 (64.7%) patients. Further, plasmapheresis was used in 9/17 (52.9%), steroids in 5/17 (29.4%), cyclophosphamide in 3/17 (17.6%), calcium channel blockers in 3/17 (17.6%), and Rituximab in 3/17 (17.6%) patients. Renal replacement therapy was required in 11/17 (64.7%) patients. 14/17 patients (82.3%) were reported to have clinical (renal or hematologic) improvement with Eculizumab therapy (Table 1).
CONCLUSION
These findings should prompt testing on a larger cohort of SRC-TMA patients. This would help us determine whether aggressive treatment combining ACE-I and Eculizumab can target the various underlying endothelial, inflammatory, and immunologic mechanisms involved in SRC-TMA, and improve patient outcomes.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Acute Kidney Injury; Kidney; Thrombotic Microangiopathies; Scleroderma, Systemic
PubMed: 37689027
DOI: 10.1016/j.semarthrit.2023.152256 -
JACC. Heart Failure Apr 2024Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is).
OBJECTIVES
The authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF.
METHODS
The authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality.
RESULTS
The authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%.
CONCLUSIONS
In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.
Topics: Humans; Angiotensin Receptor Antagonists; Digoxin; Heart Failure; Network Meta-Analysis; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 37656079
DOI: 10.1016/j.jchf.2023.07.014 -
BMJ Open Respiratory Research Aug 2023Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.
DESIGN
Systematic review.
ELIGIBILITY
Quantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.
DATA SOURCE
PubMed and Embase (1 January 2020-28 September 2022).
RISK OF BIAS
Cochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.
DATA ANALYSIS
Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available.
RESULTS
In all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.
CONCLUSIONS
Results from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.
PROSPERO REGISTRATION NUMBER
CRD42021292797.
Topics: Adult; Humans; COVID-19; Pandemics; SARS-CoV-2; Angiotensin Receptor Antagonists; Hydroxychloroquine; Ivermectin; Angiotensin-Converting Enzyme Inhibitors; Primary Prevention
PubMed: 37640510
DOI: 10.1136/bmjresp-2023-001674 -
Exploratory Research in Clinical and... Sep 2023Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives... (Review)
Review
BACKGROUND
Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives significantly reduce cardiovascular risks. Several studies on antihypertensives' prescribing patterns were conducted worldwide, and guidelines were developed on hypertension management. However, no systematic reviews were conducted globally to synthesize the evidence from these studies. This review aims to evaluate antihypertensives' prescription patterns, and adherence to international guidelines for hypertension management worldwide.
METHODS
Full-text antihypertensives' prescribing patterns evaluation studies were included. Reviews, commentaries, guidelines, and editorials were excluded. Various databases were searched including PubMed, Embase, and others. Studies were limited to English only and to articles published from (01/01/2010) to (20/03/2020). Crowe Critical Appraisal Tool (CCAT) was used for quality assessment.
RESULTS
The most commonly prescribed antihypertensives as monotherapy in adult patients with no comorbidities were ACEIs/ARBs (Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers), followed by CCBs (Calcium channel blockers), and BBs (Beta Blockers). Most commonly prescribed dual combinations were thiazide diuretics+ACEIs/ARBs, BBs + CCBs and CCBs+ACEIs/ARBs. Among diabetic patients, the most common agents were ACEIs/ARBs. Among patients with heart diseases, CCBs were prescribed frequently. While patients with kidney diseases, CCBs and ARBs were most prescribed. Of the 40 studies included in the review, only four studies directly assessed the prescribing patterns of antihypertensives in adherence to clinical practice guidelines. And only two studies confirmed adherence to guidelines. Furthermore, the quality of the majority of studies was moderate (50%), while 25% of articles were reported as either high or low quality.
CONCLUSION
This review revealed that there are areas for improvement for prescribing practices of antihypertensives in concordance with the latest evidence and with clinical practice guidelines.
PubMed: 37635839
DOI: 10.1016/j.rcsop.2023.100315 -
The American Journal of Cardiology Oct 2023Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with... (Meta-Analysis)
Meta-Analysis Review
Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with heart failure (HF). However, its association with improved atherosclerotic cardiovascular disease (ASCVD) events remains unclear. We performed a meta-analysis to evaluate the association of ARNI with ASCVD events in patients with HF. We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for studies comparing ARNIs with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in terms of myocardial infarction, stroke, angina pectoris, peripheral artery disease, and the composite end point in patients with HF. A total of 8 randomized controlled trials were included, with 17,541 patients assigned to either the ARNI (8,764 patients) or ACEi/ARB (8,777 patients) groups. The incidence of composite end point (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.93 to 1.13, p = 0.63), myocardial infarction (RR 1.02, 95% CI 0.81 to 1.30, p = 0.85), angina pectoris (RR 0.96, 95% CI 0.80 to 1.17, p = 0.70), and stroke (RR 0.99, 95% CI 0.85 to 1.16, p = 0.93) were not statistically different between the ARNI and ACEi/ARB groups. However, ARNI was associated with a higher incidence of peripheral artery disease (RR 1.63, 95% CI 1.05 to 2.52, p = 0.03). In conclusion, this meta-analysis found no association between ARNI therapy and improved ASCVD events in patients with HF.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Neprilysin; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Atherosclerosis; Antihypertensive Agents; Peripheral Arterial Disease; Angina Pectoris; Myocardial Infarction; Stroke; Heart Failure; Antiviral Agents
PubMed: 37619492
DOI: 10.1016/j.amjcard.2023.07.154 -
Frontiers in Pharmacology 2023To systematically assess the efficacy and safety of sacubitril/valsartan (SV) by comparison with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin...
The efficacy and safety of sacubitril/valsartan compared with ACEI/ARB in the treatment of heart failure following acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.
To systematically assess the efficacy and safety of sacubitril/valsartan (SV) by comparison with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for the treatment of heart failure caused by acute myocardial infarction (HF-AMI) based on current randomized controlled trials (RCTs). Several electronic databases were searched up to 27 May 2023. Primary endpoints were the efficacy including the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), N-terminal pro-B type natriuretic peptide (NT-proBNP) and 6-min walk test (6MWT) and secondary endpoints were the safety including the major adverse cardiovascular event (MACE) and adverse reaction (AE). A total of 14 RCTs were included and all patients were from China. Among included 1,991 patients, 997 patients received SVs and 994 patients received ACEIs/ARBs. The pooled results demonstrated that patients in the SV group showed significantly better efficacy representing as increased LVEF [weighted mean difference (WMD): 4.43%, 95% confidence interval (CI): 2.84%-6.02%, < 0.001] and 6MWT (WMD: 30.84 m, 95% CI: 25.65 m-36.03 m, < 0.001) and decreased LVEDD (WMD: -3.24 mm, 95% CI: -4.96 mm ∼ -1.52 mm, < 0.001) and NT-proBNP (WMD: -188.12 pg/mL, 95% CI: -246.75 pg/mL ∼ 129.49 pg/mL, < 0.001), which was also verified by subgroup analysis based on the history of percutaneous coronary intervention (PCI). Besides, the SV group showed significantly lower incidence rate of MACE [relative risk (RR): 0.60, 95% CI: 0.47-0.75, < 0.001] and patients receiving SVs in the non-PCI group also showed lower incidence of AE (RR: 0.38, 95% CI: 0.20-0.71, = 0.002). For the treatment of HF-AMI, SV is more effective and safer than ACEI/ARB based on current evidence, but more high-quality RCTs are still needed to verify above findings.
PubMed: 37601056
DOI: 10.3389/fphar.2023.1237210 -
The Cochrane Database of Systematic... Aug 2023Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause... (Review)
Review
BACKGROUND
Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017.
OBJECTIVES
To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.
SEARCH METHODS
We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE).
MAIN RESULTS
We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m, 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life.
AUTHORS' CONCLUSIONS
We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
Topics: Child; Adult; Humans; Adolescent; Hydroxyurea; Antisickling Agents; Acute Chest Syndrome; Captopril; Lisinopril; Creatinine; Anemia, Sickle Cell; Kidney Failure, Chronic; Proteinuria; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid
PubMed: 37539955
DOI: 10.1002/14651858.CD012380.pub3 -
Pharmaceuticals (Basel, Switzerland) Jul 2023There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation.... (Review)
Review
There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy in order to prevent the related cardiotoxicity. The present systematic review and meta-analysis of six RCTs included patients who have predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. Those patients did not have any obvious cardiac dysfunction or any previous therapy with cardioprotective agent. We evaluated the efficacy of the aforementioned medications for primary prevention of cardiotoxicity, using random effects models. Any preventive treatment did not reduce cardiotoxicity occurrence compared to controls (Odds ratios (OR) = 0.92, 95% CI 0.54-1.56, = 0.75). Results were similar for ACEIs/ARBs and beta-blockers. Treatment with ACEIs/ARBs led to a slight, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported less likelihood of discontinuation of trastuzumab treatment. More adequately powered RCTs are needed to determine the efficacy of routine prophylactic therapy.
PubMed: 37513895
DOI: 10.3390/ph16070983