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British Journal of Cancer Jan 2023The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association between the use of ACEIs and lung cancer risk.
METHODS
Records from five databases were searched from inception to 26 January 2022. Clinical studies involving persons aged ≥18 years with at least one year of follow-up and reporting adverse events, including lung cancer, were recorded with separate outcome reports supplied for the ACEIs and control groups. Data were extracted independently by three authors and pooled using a random-effects model. The primary outcome was lung cancer development. Odds ratios (ORs) with 95% confidence intervals (CIs) and lung cancer-related morbidity were calculated.
RESULTS
Of 2400 records screened, 13,061,226 patients were included from seven cohort studies and four case-control studies. Pooled results showed that ACEIs use was linked to increased lung cancer risk (OR 1.19, 95% CI 1.05-1.36; P = 0.008), with high heterogeneity (I = 98%).
CONCLUSIONS
ACEI usage is a greater risk factor for lung carcinogenesis than angiotensin receptor blocker use, especially in Asian patients. Further randomised controlled trials are needed to confirm the causal association between the use of ACEIs and lung cancer risk.
Topics: Humans; Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Risk Factors; Lung Neoplasms; Case-Control Studies
PubMed: 36396817
DOI: 10.1038/s41416-022-02029-5 -
Pharmacogenomics Feb 2019Genetic polymorphisms may influence the incidence of angiotensin-converting enzyme (ACE) inhibitor-induced cough. This study aims to investigate this association. (Meta-Analysis)
Meta-Analysis
AIM
Genetic polymorphisms may influence the incidence of angiotensin-converting enzyme (ACE) inhibitor-induced cough. This study aims to investigate this association.
METHODS
Ten electronic databases and PharmGKB were systematically searched. Pooled odds ratio values and their 95% CI were used to assess the association, using the random-effects model.
RESULTS
A total of 26 studies were included in the review, 17 of them were included from two separated meta-analysis (ACE I/D or BDKRB2-58T/C). Significant association was found between ACE I/D I carriers (ACE gene insertion) and ACE inhibitor-induced cough, showing racial and age differences.
CONCLUSION
This study demonstrated that ACE I/D but not BDKRB2-58T/C polymorphism could be a predictor for the risk of ACE inhibitor-induced cough, especially in east Asians and the aged.
Topics: Angiotensin-Converting Enzyme Inhibitors; Asian People; Cough; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Polymorphism, Genetic
PubMed: 30672376
DOI: 10.2217/pgs-2018-0157 -
Journal of the American Heart... Oct 2017The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction.
METHODS AND RESULTS
We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL-C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (-74.1%; 95% credible interval -79.81% to -68.58%), alirocumab 75 mg (-20.03%; 95% credible interval -27.32% to -12.96%), and alirocumab 150 mg (-13.63%; 95% credible interval -22.43% to -5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe.
CONCLUSIONS
PCSK9 inhibitors added to medium- to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction. The network meta-analysis showed a significant treatment difference in LDL-C reduction for evolocumab versus alirocumab.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Biomarkers; Cardiovascular Diseases; Down-Regulation; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Male; Middle Aged; PCSK9 Inhibitors; Proprotein Convertase 9; Randomized Controlled Trials as Topic; Risk Factors; Serine Proteinase Inhibitors; Treatment Outcome
PubMed: 28971955
DOI: 10.1161/JAHA.116.005367 -
Reproductive Health Apr 2016Antiretroviral therapy is recommended during pregnancy to decrease the risk of perinatal transmission of HIV-1 infection and to improve maternal health. However, some... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antiretroviral therapy is recommended during pregnancy to decrease the risk of perinatal transmission of HIV-1 infection and to improve maternal health. However, some studies have reported that antiretroviral treatment (ART) containing protease inhibitors (PI) is associated with an increased risk of preterm birth. In contrast, other studies have reported no increased risk. This meta-analysis was conducted to derive a more reliable estimate of the association between the prenatal use of PI based ART regimen and preterm birth.
METHODS
A systemic review and meta-analysis was conducted using published studies which were identified through a computerized search using the Medline/PubMed database, Google Scholar and Health Inter Network Access to Research Initiative (HINARI). The analysis was undertaken using STATA version 11.0 software and studies were described by forest plot. Heterogeneity across studies was checked using Cochran Q test and I2 test. An adjusted odd ratio with 95% confidence intervals [95% CI] was pooled using a random effects model.
RESULTS
The Cochrane Q test (Q test p = 0.051) showed a good homogeneity among studies. However, medium heterogeneity was observed in up to 46% of the sample using the I2 test (I2 = 46.5%). The Egger weighted regression method (p = 0.04) showed evidence of publication bias, but Begg rank correlation statistics (p = 0.47) did not show evidence of publication bias. The pooled analysis of 10 studies showed that protease based ART exposure during pregnancy was associated with an increased risk of preterm birth (pooled odds ratio 1.32 (95% CI, 1.04 to 1.59).
CONCLUSIONS
This meta-analysis revealed that the PI based ART exposure during pregnancy is significantly associated with an increased risk of preterm birth. There should be strong cautions against initiating ART during pregnancy and PI based ARV should be replaced by others drug regime. Protease inhibitor ART drugs should not be included as part of therapy during pregnancy.
Topics: Adult; Antiretroviral Therapy, Highly Active; Cohort Studies; Drug Monitoring; Evidence-Based Medicine; Female; HIV Infections; HIV Protease Inhibitors; Humans; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Prospective Studies; Risk Factors
PubMed: 27048501
DOI: 10.1186/s12978-016-0149-5 -
HIV Medicine Sep 2007The purpose of this article is to provide a systematic review of the available pharmacokinetic and clinical data on drug interactions between protease inhibitors (PIs)... (Review)
Review
OBJECTIVE
The purpose of this article is to provide a systematic review of the available pharmacokinetic and clinical data on drug interactions between protease inhibitors (PIs) and acid-reducing agents, and their clinical relevance.
METHODS
A literature search was performed using Medline and EMBASE, abstracts of the previous 2 years of major conferences were searched and the drug information service of the manufacturer of every currently available PI was contacted. All data were summarized, and verified by at least two authors.
RESULTS
A total of 1231 references were identified, 22 of which were studies of pharmacokinetic interactions between PIs and acid-suppressive agents and a further 12 of which provided pharmacokinetic and/or clinical data.
CONCLUSIONS
Many pharmacokinetic studies show a lack of a drug interaction between at least one acid-reducing agent and most PIs. Little clinical information is available, except on interactions between atazanavir and acid-reducing agents. This is probably a consequence of the complexity of the interaction.
Topics: Antacids; Drug Interactions; Female; HIV Infections; Histamine Antagonists; Humans; Male; Protease Inhibitors; Proton Pump Inhibitors
PubMed: 17661841
DOI: 10.1111/j.1468-1293.2007.00482.x -
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 -
BMJ Clinical Evidence Nov 2009Among people with diabetes, about 40% of those aged 45 years, and more than 60% of those aged 75 years and over, will have a blood pressure over 140/90 mmHg. Major... (Review)
Review
INTRODUCTION
Among people with diabetes, about 40% of those aged 45 years, and more than 60% of those aged 75 years and over, will have a blood pressure over 140/90 mmHg. Major cardiac events occur in approximately 5% of people with diabetes and untreated hypertension each year, and the risk is higher in those with other risk factors, such as diabetic nephropathy.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antihypertensives in people with diabetes and hypertension? What are the effects of different blood pressure targets in people with diabetes and hypertension? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: alpha-blockers; angiotensin II receptor antagonists; angiotensin-converting enzyme (ACE) inhibitors; beta-blockers; blood pressure targets (lower or higher); calcium-channel blockers; and diuretics.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Humans; Hypertension
PubMed: 21726474
DOI: No ID Found -
British Journal of Clinical Pharmacology Aug 2022To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing... (Meta-Analysis)
Meta-Analysis Review
AIMS
To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs).
METHODS
More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness.
RESULTS
After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid-modifying drugs (atorvastatin, 1 trial).
CONCLUSION
Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Agents; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment
PubMed: 35322889
DOI: 10.1111/bcp.15331 -
Plant Science : An International... Mar 2020Protease inhibitors (PIs) are regulatory proteins found in numerous animal tissues and fluids, plants, and microorganisms that reduce and inhibit the exacerbated and...
Protease inhibitors (PIs) are regulatory proteins found in numerous animal tissues and fluids, plants, and microorganisms that reduce and inhibit the exacerbated and uncontrolled activity of the target proteases. Specific PIs are also effective tools for inactivating proteases involved in human diseases like arthritis, pancreatitis, hepatitis, cancer, AIDS, thrombosis, emphysema, hypertension, and muscular dystrophy among others. Plant PIs-small peptides with a high content of cystine residues in disulfide bridges-possess a remarkable resistance to heat treatment and a high stability against shifts in pH, denaturing agents, ionic strength, and proteolysis. In recent years, novel biologic activities have been reported for plant PIs, including antimicrobial, anticoagulant, antioxidant action plus inhibition of tumor-cell growth; thus pointing to possible applications in medicine, agriculture, and biotechnology. In this review, we provide a comparative overview of plant-PIs classifying them in four groups according of their thermal and pH stability (high stability and hyperstable -to temperature and to pHs-, respectively), then emphasizing the relevance of the physicochemical characteristics of these proteins for potential biotechnological and industrial applications. Finally, we analyze the biologic activities of the stable protease inhibitors previously characterized that are the most relevant to potential applications in biomedicine, the food industry, and agriculture.
Topics: Agriculture; Biomedical Research; Biomedical Technology; Biotechnology; Plant Proteins; Plants; Protease Inhibitors
PubMed: 32005400
DOI: 10.1016/j.plantsci.2019.110398 -
Clinical Infectious Diseases : An... Jun 2021There have been arguments on whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) treatment alters the risk of coronavirus... (Meta-Analysis)
Meta-Analysis
The Effect of Prior Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Treatment on Coronavirus Disease 2019 (COVID-19) Susceptibility and Outcome: A Systematic Review and Meta-analysis.
There have been arguments on whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) treatment alters the risk of coronavirus disease 2019 (COVID-19) susceptibility and disease severity. We identified a total of 102 eligible studies for systematic review, in which 49 studies adjusting for confounders were included in the meta-analysis. We found no association between prior ACEI/ARB use and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population (adjusted odds ratio [aOR], 1.00; 95% confidence interval [CI], .94-1.05). The risk of mortality (aOR, .87; 95% CI, .66-1.04) and severe outcomes (aOR, .95; 95% CI, .73-1.24) were also unchanged among COVID-19 patients taking ACEIs/ARBs. These findings remained consistent in subgroup analyses stratified by populations, drug exposures, and other secondary outcomes. This systematic review provides evidence-based support to current medical guidelines and position statements that ACEIs/ARBs should not be discontinued. Additionally, there has been no evidence for initiating ACEI/ARB regimen as prevention or treatment of COVID-19.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Humans; Hypertension; SARS-CoV-2
PubMed: 33079200
DOI: 10.1093/cid/ciaa1592