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Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
Cureus Feb 2024Heart failure (HF) is a major cause of morbidity and mortality and imposes a significant financial burden on healthcare systems globally. Angiotensin receptor-neprilysin... (Review)
Review
Heart failure (HF) is a major cause of morbidity and mortality and imposes a significant financial burden on healthcare systems globally. Angiotensin receptor-neprilysin inhibitor (ARNI), a novel neuroendocrine inhibitor, is frequently used in treating HF. However, there is still limited understanding regarding how it compares to other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). The purpose of this research is to present the most recent data regarding the efficacy and renal impact of ARNIs in the treatment of HF in comparison to ACE inhibitors and ARBs. Several large-scale randomized controlled trials (RCTs) have recently been conducted to evaluate the benefits of this drug in patients with different types of HF, regardless of their renal status. We searched multiple databases, including PubMed, PubMed Central (PMC), and Google Scholar, to find relevant RCTs. The efficacy outcome was a composite of the rate of death from cardiovascular causes, the frequency of HF hospitalizations (HFH), and alterations in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The renal outcome was impairment of renal function. This systematic review analyzed large-scale RCTs involving 17,327 participants, with an average follow-up time of approximately 2.9 years. sacubitril/valsartan showed notable improvements compared to ACEis and ARBs in the following areas: reduction in NT-proBNP levels, prevention of further deterioration in renal function, and decreased hospitalizations for HF. Interestingly, there is no increased risk of mortality from cardiovascular causes with sacubitril or valsartan.
PubMed: 38516430
DOI: 10.7759/cureus.54501 -
Cureus Feb 2024Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are commonly... (Review)
Review
A Comparative Study of the Safety and Efficacy Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Management of Hypertension: A Systematic Review.
Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are commonly used in the management of hypertension. High blood pressure is a vital risk factor for cardiovascular disease. This study aims to establish any significant difference in using ACEIs and ARBs in managing hypertension. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct this systematic review. We searched PubMed, MEDLINE, and ScienceDirect for articles published in the last 20 years (2003 to 2023). Our search was last done on the 27th of June, 2023. Following the initial search, 8,313 articles were found on PubMed. After screening the articles selected from the databases, 10 articles examining 1,621,445 patients were selected for the final study. Three articles were identified that compared ACEI and ARB in their capacity to lower blood pressure. Six articles compared both medications' capacity to reduce cardiovascular events and mortality. Five articles were identified that compared both classes of drugs for adverse effects. This study was made to determine whether or not there is a difference between the use of ACEIs and ARBs in the treatment of hypertension. The study showed that both ACEIs and ARBs are similar in their efficacy in lowering blood pressure. However, ACEI was revealed to be superior to ARB in reducing cardiovascular events and all-cause mortality. ARB was shown to be better tolerated by patients than ACEI.
PubMed: 38496070
DOI: 10.7759/cureus.54311 -
Cancer Medicine Mar 2024Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS
We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023.
MAIN OUTCOMES AND MEASURES
The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS
We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS AND RELEVANCE
Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Carcinoma, Non-Small-Cell Lung; Angiotensin Receptor Antagonists; Lung Neoplasms; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Aspirin; Antihypertensive Agents; Metformin
PubMed: 38491813
DOI: 10.1002/cam4.7049 -
The Canadian Journal of Cardiology Mar 2024The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well established in patients with advanced chronic kidney disease... (Review)
Review
BACKGROUND
The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well established in patients with advanced chronic kidney disease (CKD). We conducted a systematic review and meta-analysis to identify potential risks and benefits from RAAS blockade in patients with CKD stage 4-5.
METHODS
A Medline search from inception to November 2022 was conducted to identify randomised controlled trials (RCTs) in patients with CKD stage 4-5 (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m) comparing RAAS blockade vs placebo or alternative antihypertensive therapy. Different intervention strategies were assessed (RAAS use vs nonuse, initiation vs placebo/alternative therapy, or discontinuation vs continuation). The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were all-cause mortality and major adverse cardiovascular events (MACE). The risk ratio (RR) was estimated with the use of a random-effects model.
RESULTS
Nine RCTs (1150 patients) were included. RAAS blockade was associated with a significant reduction in progression to ESKD: RR 0.84 (95% confidence interval [CI] 0.74-0.96; P = 0.01). There was no benefit from RAAS blockade on all-cause mortality or MACE: RR 1.02 (95% CI 0.63-1.65; P = 0.93) and RR 0.87 (95% CI 0.49-1.57; P = 0.65), respectively.
CONCLUSIONS
RAAS blockade may be considered in selected patients with CKD stage 4-5 to delay progression to ESKD.
PubMed: 38458564
DOI: 10.1016/j.cjca.2024.02.027 -
Reproductive Biology and Endocrinology... Mar 2024Pregnancy is characterized by profound circulatory changes and compensatory adjustments in the renin-angiotensin-aldosterone system (RAAS). Differences in regulatory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pregnancy is characterized by profound circulatory changes and compensatory adjustments in the renin-angiotensin-aldosterone system (RAAS). Differences in regulatory response may antedate or accompany vascular complicated pregnancy. We performed a systematic review and meta-analysis to delineate the trajectory of active plasma renin concentration (APRC) in healthy pregnancy and compare this to complicated pregnancy.
METHODS
We performed a systematic review and meta-analysis on APRC during normotensive and hypertensive pregnancies, using PubMed (NCBI) and Embase (Ovid) databases. We included only studies reporting measurements during pregnancy together with a nonpregnant reference group measurement. Risk of bias was assessed with QUIPS. Ratio of the mean (ROM) and 95% confidence intervals (CI) of APRC values between pregnant and nonpregnant women were estimated for predefined intervals of gestational age using a random-effects model. Meta-regression was used to analyze APRC over time.
RESULTS
In total, we included 18 studies. As compared to nonpregnant, APRC significantly increased as early as the first weeks of healthy pregnancy and stayed increased throughout the whole pregnancy (ROM 2.77; 95% CI 2.26-3.39). APRC in hypertensive complicated pregnancy was not significantly different from nonpregnancy (ROM 1.32; 95% CI 0.97-1.80).
CONCLUSION
Healthy pregnancy is accompanied by a profound rise in APRC in the first trimester that is maintained until term. In hypertensive complicated pregnancy, this increase in APRC is not observed.
Topics: Pregnancy; Female; Humans; Renin; Pregnancy Complications; Hypertension; Renin-Angiotensin System; Blood Pressure; Aldosterone
PubMed: 38454417
DOI: 10.1186/s12958-024-01200-2 -
Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
Medicine Feb 2024In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review and meta-analysis are necessary to assess the efficacy and safety of SML injection for the treatment of DKD.
METHODS
We searched 6 electronic literature databases comparing randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), SML injection in combination with ACEIs/ARBs that were conducted from inception until September 5, 2023. Two reviewers extracted data and independently assessed the risk of bias. Using the Cochrane Risk of Bias Tool for Risk Assessment. Mean differences (MD) were combined with random-effects models and the corresponding 95% confidence intervals (CI) were reported. Review Manager 5.4 software was used for meta-analysis. Stata 17.0 software was used for sensitivity analysis and Egger test.
RESULTS
The combined results show that the use of SML injection along with ACEI/ARB led to better outcomes than the use of controls in terms of enhancing recovery: renal function: Serum creatinine (MD = -14.69, 95% CI (-19.38, -10.00)), Blood urea nitrogen (MD = -1.23, 95% CI (-1.72, -0.74)), Urinary β2-microglobulin (MD = -4.58, 95% CI (-7.72, -1.44)); urinary protein: Urinary albumin excretion rate (MD = -45.74, 95% CI (-58.92, -32.56)), Urine albumin-creatinine ratio (MD = -11.93, 95% CI (-13.89, -9.96)), 24-h urine proteinuria (MD = -0.59, 95% CI (-0.86, -0.32)), Urine microalbumin (MD = -13.50, 95% CI (-20.18, -6.83)). Additionally, adjuvant therapy with SML injection enhanced results in blood glucose, blood pressure, lipids, and inflammatory responses, and no significant variations in adverse events were discovered between the 2 groups.
CONCLUSIONS
In patients with DKD, combining SML injection with ACEI/ARB improves renal function, renal proteinuria, hyperglycemia, blood pressure, dyslipidemia, and inflammatory response.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Salvia miltiorrhiza; Proteinuria; Albumins; Angiotensin Receptor Antagonists; Diabetes Mellitus; Pyrazines
PubMed: 38394516
DOI: 10.1097/MD.0000000000035853 -
JAMA Cardiology Apr 2024Implementation of guideline-directed medical therapy (GDMT) in real-world practice remains suboptimal. It is unclear which interventions are most effective at addressing...
IMPORTANCE
Implementation of guideline-directed medical therapy (GDMT) in real-world practice remains suboptimal. It is unclear which interventions are most effective at addressing current barriers to GDMT in patients with heart failure with reduced ejection fraction (HFrEF).
OBJECTIVE
To perform a systematic review to identify which types of system-level initiatives are most effective at improving GDMT use among patients with HFrEF.
EVIDENCE REVIEW
PubMed, Embase, Cochrane, CINAHL, and Web of Science databases were queried from January 2010 to November 2023 for randomized clinical trials that implemented a quality improvement intervention with GDMT use as a primary or secondary outcome. References from related review articles were also included for screening. Quality of studies and bias assessment were graded based on the Cochrane Risk of Bias tool and Oxford Centre for Evidence-Based Medicine.
FINDINGS
Twenty-eight randomized clinical trials were included with an aggregate sample size of 19 840 patients. Studies were broadly categorized as interdisciplinary interventions (n = 15), clinician education (n = 5), electronic health record initiatives (n = 6), or patient education (n = 2). Overall, interdisciplinary titration clinics were associated with significant increases in the proportion of patients on target doses of GDMT with a 10% to 60% and 2% to 53% greater proportion of patients on target doses of β-blockers and renin-angiotensin-aldosterone system inhibitors, respectively, in intervention groups compared with usual care. Other interventions, such as audits, clinician and patient education, or electronic health record alerts, were also associated with some improvements in GDMT utilization, though these findings were inconsistent across studies.
CONCLUSIONS AND RELEVANCE
This review summarizes interventions aimed at optimization of GDMT in clinical practice. Initiatives that used interdisciplinary teams, largely comprised of nurses and pharmacists, most consistently led to improvements in GDMT. Additional large, randomized studies are necessary to better understand other types of interventions, as well as their long-term efficacy and sustainability.
Topics: Humans; Heart Failure; Stroke Volume; Adrenergic beta-Antagonists; Ventricular Dysfunction, Left; Quality Improvement
PubMed: 38381449
DOI: 10.1001/jamacardio.2023.5627 -
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