Angiotensin-converting enzyme inhibitors decrease the risk of radiation pneumonitis after stereotactic body radiation therapy

Postradiation White Blood Cell Count Is a Novel Marker of Radiation Pneumonitis in Non-Small Cell Lung Cancer

Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non-small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size ( P = .041), mean lung dose ( P = .028), V2.5 ( P = .024), V5 ( P = .014), V10 ( P = .004), V20 ( P = .024), V30 ( P = .020), V40 ( P = .040), and V50 ( P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 ( P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

Symptomatic Radiation Pneumonitis in Elderly Patients Receiving Thoracic Irradiation

The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of cancer. We evaluated associations between use of angiotensin-converting enzyme (ACE) inhibitors and of angiotensin receptor blockers (ARBs) and keratinocyte cancer incidence in a population at high risk of the disease. A cohort study design was conducted using data on 1051 participants in the randomized Department of Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial, all of whom were at increased risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). We followed participants from enrollment (November 1998 through January 2003) until first BCC or SCC. Study participants were examined every 6 months by a study dermatologist; biopsies were taken on all suspicious lesions and centrally reviewed. Use of ACE inhibitors and ARBs was ascertained from VA pharmacy records. Cox proportional hazards models were used to estimate adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of BCC and SCC with use of ACE inhibitors or ARBs. During a median follow-up of 3.4 years, 472 incident BCCs, 309 SCCs, and 200 deaths from any cause were observed. Compared with nonusers, users of ACE inhibitors or ARBs had statistically significantly reduced risks of BCC (IRR(BCC) = 0.61, 95% CI = 0.50 to 0.76) and SCC (IRR(SCC) = 0.67, 95% CI = 0.52 to 0.87). The combined absolute incidence rates of BCC and SCC were 237 per 1000 person-years among users of ACE inhibitors or ARBs and 374 per 1000 person-years among nonusers. The greatest reduction in keratinocyte cancer was seen among people who initiated use of ACE inhibitors or ARBs during the study period (IRR(BCC) = 0.45 [95% CI = 0.34 to 0.59]; IRR(SCC) = 0.48 [95% CI = 0.35 to 0.67]). Among a high-risk group of veterans, users of ACE inhibitors or ARBs had a lower incidence of keratinocyte cancers than nonusers. The more pronounced reduction among those who initiated use during the study may indicate an immediate effect.

Introduction: Given the limited evidence, we investigated the association between use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and risk of Covid-19 infection within a large diverse hypertension population. Methods: We identified patients with hypertension as of March 1, 2020 (index date) from Kaiser Permanente Southern California, a large US integrated healthcare system. Patient demographics, antihypertensive medication use, neighborhood income and education, and comorbidities were identified from electronic health records within 1-year pre-index date. The study outcome was a positive RT-PCR test for Covid-19 between March 1 - May 6, 2020. We used multivariable logistic regression models to examine the association between ACEI/ARB use and Covid-19 infection. Results: Among 824,650 patients with hypertension, 16,898 (2.0%) were tested for Covid-19. Of those tested, 1,794 (10.6%) had a positive result and 547 (30.5% of positive cases) were hospitalized within 14-days of testing positive. Of those tested, 4,878 (28.9%) were on ACEIs, 3,473 (20.6%) were on ARBs, and 4,177 (24.7%) were on other antihypertensive medication classes. Risk of covid-19 infection associated with ACEI use decreased with increasing age (P-interaction = 0.01). In age-stratified analyses, ACEI use was not statistically associated with increased risk of Covid-19 infection among the age groups of 18-39, 40-64, and 65-84 years but was associated with lower risk of Covid-19 among those aged ≥85 years ( Table ). Across all age groups, ARB use was not associated with increased risk of Covid-19, but non-white race, lower neighborhood income and education, and no antihypertensive medication use were associated with increased risk of Covid-19. Conclusions: ACEI nor ARB use was not associated with increased risk of Covid-19 infection. The decreased risk of Covid-19 infection among older adults using ACEIs warrants further investigation.

The extent to which age plays a role in the underutilization of angiotensin-converting enzyme (ACE) inhibitors in heart failure patients has not been well studied. We studied age-related variation in the use of ACE inhibitors in older Medicare beneficiaries discharged alive in Alabama with a diagnosis of heart failure with left ventricular systolic dysfunction. A total of 285 patients had a mean age +/- SD of 78 +/- 6.9 years; 59% were female and 21% were African American. Of the 285 patients, 181 (63%) were prescribed ACE inhibitors at discharge. Therapy with ACE inhibitors was initiated in 47% of the patients. Compared with patients 65 to 74 years, those 85 years and older had lower odds of receiving ACE inhibitors at discharge. Among patients not admitted on an ACE inhibitor, those 85 years and older also had lower odds of ACE inhibitor therapy being initiated. The overall rate of ACE inhibitor use was low, and age of 85 years and older was independently associated with lower use and initiation of ACE inhibitors. Opportunities remain to increase the use of ACE inhibitors in older patients with heart failure.

Large-scale, placebo-controlled, randomized clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) reduce mortality and hospitalization in patients with heart failure (HF) caused by left ventricular systolic dysfunction (LVSD). However, it is unknown whether ACE inhibitors and ARBs have similar effects on the long-term outcomes in HF patients encountered in routine clinical practice. The Japanese Cardiac Registry of Heart Failure in Cardiology enrolled HF patients hospitalized with worsening symptoms and they were followed during an average of 2.2 years. The outcome data were compared in patients with LVSD by echocardiography (ejection fraction, EF <40%) according to the predischarge use of ACE inhibitors (n=356) or ARBs (n=372). The clinical characteristics were similar between patients with ACE inhibitor and ARB use, except for higher prevalence of hypertensive etiology and diabetes mellitus. There was no significant difference between ACE inhibitor and ARB use in all-cause death (adjusted hazard ratio 0.958, 95% confidence interval 0.601-1.527, P=0.858) and rehospitalization (adjusted hazard ratio 0.964, 95% confidence interval 0.683-1.362, P=0.836). The effects of ACE inhibitor and ARB use on the outcomes were generally consistent across all clinically relevant subgroups examined, including age, sex, etiology, EF, hypertension, diabetes mellitus, and beta-blocker use. Discharge use of ARBs provided comparable effects with ACE inhibitors on outcomes in patients hospitalized for HF. These findings provide further support for guideline recommendations that ARBs can be used in patients with HF and LVSD as an alternative of ACE inhibitors.

Several well-controlled trials in patients with heart failure have shown that the use of angiotensin-converting enzyme (ACE) inhibitors, in combination with a diuretic, causes a reduction in mortality and morbidity,...

Although a considerable volume of data supporting induction or aggravation of psoriasis because of angiotensin-converting enzyme (ACE) inhibitor use exists, it remains insufficient for definitive conclusions. Therefore, we aimed to evaluate the association between ACE inhibitor use and psoriasis incidence through a systematic literature review and meta-analysis. We searched for qualifying studies across PubMed, Web of Science, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between ACE inhibitor use and psoriasis incidence. Eight studies with a total of 54,509 patients with a psoriasis diagnosis were included in this meta-analysis. The pooled OR for psoriasis incidence among ACE inhibitor users was 1.52 (95% CI, 1.16–2.00) compared to that among non-users. From subgroup analysis by continent, the OR for ACE inhibitor users versus non-users was 2.37 (95% CI 1.28–4.37) in Asia. Per the subgroup analysis by climate, the OR for ACE inhibitor users vs non-users in dry climate was 3.45 (95% CI: 2.05–5.79) vs 1.32 (95% CI 1.01–1.73) in temperate climate. Our results reveal a significant association between ACE inhibitor use and psoriasis incidence.

Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-β) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-β signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan–Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.

It has been suggested that use of the antihypertensive drugs angiotensin-converting enzyme (ACE) inhibitors and β-blockers may decrease the risk of primary liver cancer; thus, the objective of this study was to evaluate whether use of ACE inhibitors and/or β-blockers is associated with a lower risk of liver cancer. Nested case-control study. United Kingdom Clinical Practice Research Datalink. We identified 490 cases with hypertension and a first-time (incident) diagnosis of primary liver cancer between 1988 and 2011. To account for an induction period, the index date was defined as the date of the first recorded liver cancer diagnosis minus 1year. Controls were selected from patients with hypertension in the CPRD during the study period with a recorded diagnosis of hypertension who had no diagnosis of liver cancer and were free of any other cancer (except nonmelanoma skin cancer) before the index date; they were matched up to a 4:1 ratio to cases based on index date (same index date as that of their matched case), age (same year of birth), sex, general practice, and number of years of recorded history in the CPRD before the index date (1909 controls). Both cases and controls were required to have at least 2years of recorded activity in the database before the index date. Exposure was defined as receipt of two or more prescriptions for ACE inhibitors and/or β-blockers before the index date; the reference group was nonuse (0-1 prescription) of ACE or β-blocker prescriptions before the index date. We also examined the effect of duration of use and, separately, the effect of individual drugs within each medication class on risk of liver cancer, and conducted analyses restricted to patients without liver disease or diabetes mellitus. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). No association was found between use of ACE inhibitors and/or β-blockers and the risk of liver cancer compared with nonuse (adjusted OR 1.14, 95% CI 0.85-1.55). No significant differences were noted in risk by duration of use or by individual drugs, or after restricting the analyses to patients without diabetes or liver disease. Use of ACE inhibitors and/or β-blockers was not associated with reduced risk of primary liver cancer compared with nonuse of these drugs in persons with hypertension.

The authors identified 321 elderly Kansas Medicaid patients with congestive heart failure and examined angiotensin-converting enzyme (ACE) inhibitor use. Using retrospective claims data, ACE inhibitor use was quantified and daily doses compared to a target enalapril-equivalent dose of 20 mg. The cohort patients averaged 80 years of age, 84% were female, and 70% resided primarily in a nursing home. Only 37.8% received an ACE inhibitor. Users were younger than nonusers (t=2.00; p=0.046), but there was no gender difference (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.73, 2.6). ACE inhibitor users averaged eight prescriptions annually, providing approximately 257 medication days (70% of the study period). The average enalapril-equivalent daily dose was 10.6 mg, and only 22% received the target dose. Nursing home residents were less likely to receive an ACE inhibitor than ambulatory patients (OR, 0.55; 95% CI, 0.34, 0.89) but equally likely to receive target doses (OR, 1.3; 95% CI, 0.34, 4.9). ACE inhibitor use in the Kansas Medicaid congestive heart failure population is not consistent with practice guidelines, particularly among older and/or nursing home patients.

PurposeAlthough stereotactic ablative body radiotherapy (SABR) is widely used therapeutic technique, predictive factors of radiation pneumonitis (RP) after SABR remain undefined. We aimed to investigate the predictive factors affecting RP in patients with primary or metastatic lung tumors who received SABR.Materials and MethodsFrom 2012 to 2015, we reviewed 59 patients with 72 primary or metastatic lung tumors treated with SABR, and performed analyses of clinical and dosimetric variables related to symptomatic RP. SABR was delivered as 45–60 Gy in 3–4 fractions, which were over 100 Gy in BED when the α/β value was assumed to be 10. Tumor volume and other various dose volume factors were analyzed using median value as a cutoff value. RP was graded per the Common Terminology Criteria for Adverse Events v4.03.ResultsAt the median follow-up period of 11 months, symptomatic RP was observed in 13 lesions (12 patients, 18.1%), including grade 2 RP in 11 lesions and grade 3 in 2 lesions. Patients with planning target volume (PTV) of ≤14.35 mL had significantly lower rates of symptomatic RP when compared to others (8.6% vs. 27%; p = 0.048). Rates of symptomatic RP in patients with internal gross tumor volume (iGTV) >4.21 mL were higher than with ≤4.21 mL (29.7% vs. 6.1%; p = 0.017).conclusionsThe incidence of symptomatic RP following treatment with SABR was acceptable with grade 2 RP being observed in most patients. iGTV over 4.21 mL and PTV of over 14.35 mL were significant predictive factors related to symptomatic RP.

To assess the current evidence on the potential benefit of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on cancer recurrence and survival, we comprehensively searched PubMed, Embase, and the Cochrane Library from their inception to April 2013. Two authors screened out duplicates and independently reviewed the eligibility of each study. We included comparative studies comparing the use and nonuse of ACEIs or ARBs in cancer patients. Primary outcomes were disease-free survival (DFS) and overall survival. We included 11 studies with 4964 participants in the final analysis. The meta-analysis showed that the use of ACEIs or ARBs resulted in a significant improvement in DFS [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41-0.87; P=0.007)] and overall survival (HR 0.75; 95% CI 0.57-0.99; P=0.04). Even when cancer stage was classified into low (I/II) or high (III/IV), DFS improvement was applied to both low stage (HR 0.56; 95% CI 0.32-0.96; P=0.04) and high stage (HR 0.59; 95% CI 0.37-0.94; P=0.03). Analysis according to cancer type showed benefits in urinary tract cancer (HR 0.22), colorectal cancer (HR 0.22), pancreatic cancer (HR 0.58), and prostate cancer (HR 0.14), but not in breast cancer and hepatocellular cancer. This meta-analysis provides evidence that the use of ACEIs or ARBs in cancer patients can lead to a 40 and 25% reduction in the risk of cancer recurrence and mortality.

Subclinical interstitial lung disease: Is it a risk factor for fatal radiation pneumonitis following stereotactic body radiotherapy?