Angiotensin converting enzyme inhibitors and incidence of lung cancer in a population based cohort of common data model in Korea.
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SUBMITTER: Lee SH
PROVIDER: S-EPMC8448874 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine whether the use of angiotensin converting enzyme inhibitors (ACEIs), compared with use of angiotensin receptor blockers, is associated with an increased risk of lung cancer.DesignPopulation based cohort study.SettingUnited Kingdom Clinical Practice Research Datalink.ParticipantsA cohort of 992?061 patients newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2015 was identified and followed until 31 December 2016.Main outcome measuresCox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident lung cancer associated with the time varying use of ACEIs, compared with use of angiotensin receptor blockers, overall, by cumulative duration of use, and by time since initiation.ResultsThe cohort was followed for a mean of 6.4 (SD 4.7) years, generating 7952 incident lung cancer events (crude incidence 1.3 (95% confidence interval 1.2 to 1.3) per 1000 person years). Overall, use of ACEIs was associated with an increased risk of lung cancer (incidence rate 1.6 v 1.2 per 1000 person years; hazard ratio 1.14, 95% confidence interval 1.01 to 1.29), compared with use of angiotensin receptor blockers. Hazard ratios gradually increased with longer durations of use, with an association evident after five years of use (hazard ratio 1.22, 1.06 to 1.40) and peaking after more than 10 years of use (1.31, 1.08 to 1.59). Similar findings were observed with time since initiation.ConclusionsIn this population based cohort study, the use of ACEIs was associated with an increased risk of lung cancer. The association was particularly elevated among people using ACEIs for more than five years. Additional studies, with long term follow-up, are needed to investigate the effects of these drugs on incidence of lung cancer.
| S-EPMC6199558 | biostudies-literature
Project description:Angiotensin-converting enzyme inhibitors (ACE-I) are widely used in diseases, such as hypertension, congestive heart failure, and myocardial infarction. Although these drugs are well tolerated, one out of five patients discontinues ACE-I due to drug side effects, mainly chronic cough. However, the pathogenesis of ACE-I-induced cough remains controversial and requires further study. In this review, the mechanisms that are suggested in ACE-I-induced cough pathophysiology will be discussed in detail in light of the current literature.
| S-EPMC6340691 | biostudies-literature
Project description:Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78-0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66-0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk.
| S-EPMC4902497 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.
| S-EPMC7129862 | biostudies-literature
Project description:ImportanceThe renin-angiotensin system has been implicated in mood disorders. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the most commonly used medications, yet their effects on mental health outcomes, particularly suicide, are poorly understood. This study examined the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, it was speculated that ARBs would be associated with a higher risk of suicide than ACEIs.ObjectiveTo examine the association between suicide and exposure to ARBs compared with ACEIs.Design, setting, and participantsThis population-based nested case-control study of individuals aged 66 years and older used administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019. Cases were individuals who died by suicide within 100 days of receiving an ACEI or ARB. The date of death served as the index date. For each case, 4 controls were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All individuals received an ACEI or ARB within 100 days before the index date.ExposuresUse of an ACEI or ARB.Main outcomes and measuresConditional logistic regression was used to estimate odds ratios for the association between suicide and exposure to ARBs compared with ACEIs.ResultsNine hundred sixty-four cases were matched to 3856 controls. The median (interquartile range) age of cases and controls was 76 (70-82) years. Most cases (768 [79.7%]) and controls (3068 [79.6%]) were men. Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, 741 (74.0%) were exposed to ARBs, and 3115 (81.6%) were exposed to ACEIs. Compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98).Conclusions and relevanceThe use of ARBs may be associated with an increased risk of suicide compared with ACEIs. Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.
| S-EPMC6806420 | biostudies-literature
Project description:Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been demonstrated to mitigate radiation-induced lung damage in animal models and preclinical studies. Our study aims to evaluate whether ACEIs or ARBs reduce the incidence of radiation-induced pneumonitis (RP) in lung cancer patients. Methods: Publications were searched from EMBASE, PubMed and Web of Science databases. Seven studies published from April 2000 to August 2016 met inclusion criteria and included 1412 patients in total. Only patients with grade 2 and above pneumonitis within 12 months after radiotherapy were analyzed. Results: Patients taking ACEIs had a lower risk of developing radiation pneumonitis compared with non-users (OR = 0.46, 95%CI = 0.31-0.67, p < 0.0001). While the use of ARBs couldn't reduce the incidence of RP (OR = 1.42, 95%CI = 0.94-2.14, p = 0.10). Elderly patients (age ? 70) benefited more from ACEIs (OR = 0.12, 95%CI = 0.02-0.67, p = 0.02). In addition, smokers were found to have a lower risk of developing RP than non-smokers (OR = 0.49, 95%CI = 0.30-0.81, p = 0.005), but sex and the use of statin or NSAID had no influence on the appearance of RP (p = 0.59, p = 0.70, p = 0.40, respectively). Conclusions: ACE inhibitors could decrease the incidence of symptomatic RP among lung cancer patients. However, the use of ARBs has a slight trend to develop RP but not above statistical significance. Elderly patients (age ? 70) benefited the most from ACEIs.
| S-EPMC6010681 | biostudies-literature
Project description:The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. In this sense, ACE inhibitors are bioactive substances with potential use as medicinal products for treatment or prevention of hypertension, heart failures, myocardial infarction, and other important diseases. This review examined the most recent literature reporting ACE inhibitors with the help of molecular modeling. The examples exposed here demonstrate that molecular modeling methods, including docking, molecular dynamics (MD) simulations, quantitative structure-activity relationship (QSAR), etc, are essential for a complete structural picture of the mode of action of ACE inhibitors, where molecular docking has a key role. Examples show that too many works identified ACE inhibitory activities of natural peptides and peptides obtained from hydrolysates. In addition, other works report non-peptide compounds extracted from natural sources and synthetic compounds. In all these cases, molecular docking was used to provide explanation of the chemical interactions between inhibitors and the ACE binding sites. For docking applications, most of the examples exposed here do not consider that: (i) ACE has two domains (nACE and cACE) with available X-ray structures, which are relevant for the design of selective inhibitors, and (ii) nACE and cACE binding sites have large dimensions, which leads to non-reliable solutions during docking calculations. In support of the solution of these problems, the structural information found in Protein Data Bank (PDB) was used to perform an interaction fingerprints (IFPs) analysis applied on both nACE and cACE domains. This analysis provides plots that identify the chemical interactions between ligands and both ACE binding sites, which can be used to guide docking experiments in the search of selective natural components or novel drugs. In addition, the use of hydrogen bond constraints in the S2 and S2' subsites of nACE and cACE are suggested to guarantee that docking solutions are reliable.
| S-EPMC7024173 | biostudies-literature
Project description:Angiotensin converting enzyme (ACE) is well known for its dual actions to convert inactive Ang I to active Ang II, and degrades active bradykinin (BK), which plays an important role in controlling blood pressure. Because it is the bottleneck step for the production of pressor Ang II, it was targeted pharmacologically in the 1970s. Successful ACE inhibitors such as captopril were produced to treat hypertension. Studies on domain-specific ACE inhibitors are continuing to produce effective hypertension-controlling drugs with fewer side effects. ACE2 was discovered in 2000 and it converts Ang II into Ang(1–7), thereby reducing the concentration of Ang II as well as increasing that of Ang(1–7), an important enzyme for Ang(1–7)/Mas receptor signaling. ACE2 also acts as the receptor in the lung for the coronavirus, causing the infamous severe acute respiratory syndrome (SARS) in 2003.
| S-EPMC8361046 | biostudies-literature
Project description:ObjectivesTo analyze the association of the use of different doses of angiotensin II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) independently with lung cancer risk and to evaluate the lung cancer type that may be related to ARB or ACEI use.Patients and methodsA nationwide population-based nested case-control study was conducted using Taiwan National Health Insurance Research Database linked to the Taiwan Cancer Registry database between January 1, 2000, and December 31, 2016. The cumulative defined daily dose (DDD) was estimated. We divided all users of ACEI or ARB into three categories based on the DDD of ACEI or ARB: low dose, middle dose, and high dose.ResultsWe identified 16,091 patients with newly diagnosed lung cancer, and 80,455 controls with hypertension were selected. Univariate and multivariate conditional logistic regressions showed that the independent risk factor for lung cancer was high-dose (≥ 1095 DDD) ARB use (adjusted odds ratio [OR]: 1.069, 95% confidence interval [CI]: 1.02-1.12, P = 0.003). An increase in lung adenocarcinoma (ADC) risk was associated with middle-dose (adjusted OR: 1.073, 95% CI: 1.01-1.14, P = 0.025) to high-dose (adjusted OR: 1.106, 95% CI: 1.05-1.17, P < 0.001) ARB use and high-dose ACEI use (adjusted OR: 1.095, 95% CI: 1.01-1.19, P = 0.033). No association was observed between different ARB or ACEI dose levels and the risk of lung squamous cell carcinoma and small-cell lung carcinoma.ConclusionsOur results suggest that the use of both ACEI and ARB at a high cumulative dose is associated with the risk of lung ADC.
| S-EPMC7653586 | biostudies-literature
Project description:BackgroundWe performed a meta-analysis to determine whether a consistent relationship exists between the use of angiotensin converting enzyme inhibitors (ACEIs) and the risk of lung cancer. Accordingly, we summarized and reviewed previously published quantitative studies.MethodsEligible studies with reference lists published before June 1st, 2019 were obtained from searching several databases. Random effects' models were used to summarize the overall estimate of the multivariate adjusted odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThirteen observational studies involving 458,686 ACEI users were included in the analysis, Overall, pooled risk ratios indicate that ACEIs use was not a risk factor for lung cancer (RR 0.982, 95% C.I. 0.873 - 1.104; P = .76). There was significant heterogeneity between the studies (Q = 52.54; P < .001; I2 = 86.07). There was no significant association between ACEIs use and lung cancer in studies with over five years of ACEIs exposure (RR 0.95, 95% C.I. 0.75 - 1.20; P = .70); and ≤ 5years of exposure to ACEIs (RR 0.98, 95% C.I. 0.83 - 1.15; P = .77). There were no statistically significant differences in the pooled risk ratio obtained according to the study design (Q = 0.65; P = .723) and the comparator regimen (Q = 3.37; P = .19).ConclusionsThe use of ACEIs was not associated with an increased risk of lung cancer. Nevertheless, well-designed observational studies with different ethnic populations are still needed to evaluate the long-term (over 10 years) association between ACEIs use and lung cancer.
| S-EPMC8084080 | biostudies-literature