Angiotensin-converting Enzyme Inhibitors Users Research Articles

The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough.

Background/AimsGastroesophageal reflux disease (GERD) is one of the main causes of chronic cough. We evaluated the role of microaspiration in the pathogenesis of reflux-related cough by determining the amount of lipid-laden macrophages (LLMs) in bronchoalveolar lavage (BAL) specimens.MethodsA total of 161 cases of chronic cough were evaluated, and 36 patients (average age 48.2 years) were recruited for this single center prospective study. Patients with a history of smoking, angiotensin converting enzyme inhibitor usage, any abnormality on pulmonary function tests, abnormal chest X-rays, occupational or environmental exposures, or upper airway cough syndrome were excluded. GERD was evaluated by 24-hour esophageal impedance-pH monitoring. BAL specimens for LLM determination were obtained from 34 patients by flexible bronchoscopy.ResultsPatients with pathological intra-esophageal reflux according to multichannel intraluminal impedance and pH monitoring had higher LLM positivity in BAL specimens than patients without pathological reflux (8/14 in reflux positive group vs 1/22 in reflux negative group; P = 0.004). The BAL cell distribution was not different between the 2 groups (P = 0.574 for macrophages, P = 0.348 for lymphocytes, P = 0.873 for neutrophils and P = 0.450 for eosinophils).ConclusionsOur results confirm the role of the microaspiration of refluxate in the pathogenetic mechanism of chronic cough. While bronchoscopy is indicated in patients with chronic cough, in addition to the routine airway evaluation, BAL and LLM detection should be performed. LLM can be used to diagnose aspiration in reflux-related chronic cough. Future studies are needed to evaluate the response to anti-reflux medications or surgery in patients with LLM positivity.

The Significance of Angiotensin Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Use in Sudden Cardiac Death

Objectives: To investigate the relationship between the use of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) and hyperkalemia in patients diagnosed with sudden cardiac death. Methods: We examined oral ACE inhibitor or ARB use among cardiopulmonary arrest patients brought by ambulance to our emergency room during a 5-year period from January 2012 to December 2016. The cause of death was determined to be sudden cardiac death, despite temporary return of spontaneous circulation after starting cardiopulmonary resuscitation. Subjects were dichotomized into 2 groups, those taking and those not taking an ACE inhibitor or ARB. Variables determined retrospectively included serum potassium, estimated glomerular filtration rate as an index of kidney function and time from cardiopulmonary arrest to return of spontaneous circulation. The Mann-Whitney U-test was used to compare continuous data, and the chi-square test to compare categorical data between groups. The results are expressed as the median plus range. Statistical significance was assumed at p < 0.05. Results: Thirty-five patients met the inclusion criteria. The mean age was 77.1 years (range, 35 - 93 years), and there were 26 males and 9 females. Eleven subjects were ACE inhibitor or ARB users, and 24 were non-users. The serum potassium level was significantly higher in users than non-users (median, 6.2 mEq/L (range, 4.5 - 10.0) vs. 5.2 mEq/L (range, 3.6 - 8.3); p = 0.001). The estimated glomerular filtration rate was significantly lower in users than non-users (median, 25.1 mL/min/1.73 m2 (range, 4.6 - 60.3) vs. 46.9 mL/min/1.73 m2 (range, 19.8 - 97.1); p = 0.009). There was no significant difference in time from cardiopulmonary arrest to return of spontaneous circulation between the 2 groups (median, 24 minutes (range, 3 - 111) vs. 29 minutes (range, 10 - 54); p = 0.355). Conclusion: It is possible that hyperkalemia induced by ACE inhibitor or ARB use is a cause of sudden cardiac death, especially in patients with chronic kidney disease.

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria

Background/Aims: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. Methods: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. Results: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). Conclusions: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively.

ACE inhibitors and the risk of fractures: a meta-analysis of observational studies.

A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01-1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73-1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89-1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53-3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

QTc interval in young Gujarati hypertensives: Effect of disease, antihypertensive monotherapy, and coexisting risk factors.

Objectives:To study the effect of disease duration, treatment and risk factors on QTc interval among young hypertensives.Materials and Methods:A case–control study was conducted on 142 hypertensives (60 males, 82 females) taking calcium channel blocker (CCB) or angiotensin-converting enzyme inhibitor (ACEI) as monotherapy. After blood pressure measurement, we recorded lead II electrocardiograph with minimum ten waveforms. QTc was derived from average of ten values using Bazett's formula. QTc interval >0.43 s in male and >0.45 s in female was considered abnormal.Results:Cases had mean duration of hypertension 5 years, mean age of 40 years, and poor blood pressure control (systolic blood pressure >140 and diastolic blood pressure >90 mm of Hg). Newly diagnosed hypertensives had significantly higher QTc values than the matched known cases (0.44 vs. 0.42 s, P < 0.05). Known hypertensives did not differ significantly in QTc values by the duration of disease. CCB users showed small, insignificant disadvantage for abnormally prolonged QTc values than ACEI users. With coexisting diabetes, smoking, and positive family history of hypertension, there was odds risk of 7.69, 2.75, and 2.54, respectively for prolonged QTc.Conclusion:Our study showed prolonged QTc in hypertensives more so in newly diagnosed, unaffected by duration or use of ACEI, or CCB but associated with modifiable risk factors. This underscores high risk of repolarization abnormality-induced future events, suggesting early screening of hypertension, strict blood pressure control, optimum use of QTc measurement, and preventive pharmacotherapy to reduce this aftermath.

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink.

The aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population. Two nested case-control studies were conducted in a cohort of 276 977 patients aged ≥45years initiating ACEIs from 2007 to 2014 in the UK Clinical Practice Research Datalink (CPRD). Cases of AE occurring for the first time during ACEI therapy (n = 416) were matched with AE-free controls (n = 4335) on the duration of ACEI treatment. Documented switches to angiotensin-II receptor blockers in the prescription records were used to identify ACEI-intolerance cases (n = 24 709), and these were matched with continuous ACEI users (n = 84 238) on the duration of ACEI therapy. Conditional logistic regression was used to assess the associations of demographic factors, comorbidities and comedication with AE and ACEI intolerance. AE during ACEI therapy was associated with age over 65years [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.07, 1.73], history of allergy (OR 1.53, 95% CI 1.19, 1.96), use of calcium channel blockers (OR 1.57, 95% CI 1.23; 2.01), use of antihistamines (OR 21.25, 95% CI 16.44, 27.46) and use of systemic corticosteroids (OR 4.52, 95% CI 3.26, 6.27). ACEI intolerance was significantly associated with more comorbidities and comedication compared with AE, including allergy (OR 2.02, 95% CI 1.96, 2.09), use of antiasthmatic drugs (OR 1.51, 95% CI 1.42, 1.61) and use of antihistamines (OR 1.53, 95% CI 1.43, 1.63). Among ACEI users developing AE or ACEI intolerance, several comorbidities and comedication classes were significantly more prevalent compared with ACEI users not developing these adverse reactions.

Angiotensin-Converting Enzyme Inhibitors and Parameters of Sarcopenia: Relation to Muscle Mass, Strength and Function: Data from the Berlin Aging Study-II (BASE-II)

Pharmacological options for the treatment of sarcopenia currently do not exist. However, off-label treatment options of some established drugs have been suggested. The aim of this study was to assess differences in various muscle and physical performance parameters in relation to the intake of angiotensin-converting enzyme (ACE) inhibitors in a cohort of community-dwelling older people. Eight hundred and thirty-eight participants from the Berlin Aging Study-II (BASE-II) were included. Appendicular lean mass was assessed with dual-energy X-ray absorptiometry and related to height and body mass index. Muscle strength was measured by grip strength and related to muscle mass (arm muscle quality) and functional status was assessed via the timed "Up and Go" test. Users of ACE inhibitors had higher lean mass related to height but significantly lower lean mass related to body mass index (p=0.001 for women and p<0.0001 for men). Moreover, they exhibited lower arm muscle quality (p=0.032 for women and p=0.031 for men) and reported difficulties in climbing stairs more often than non-users (p=0.014 for women and p=0.004 for men). After adjustment for confounders, there were no significant differences regarding lean mass, arm muscle quality and the timed "Up and Go" test according to the use of ACE inhibitors. In BASE-II, no positive relationship was found between the intake of ACE inhibitors and lean mass, strength, muscle quality or function. Moreover, remarkable differences between parameters of absolute and relative lean mass in relation to the use of ACE inhibitors became evident. Fat mass proved to be an important confounder and therefore muscle mass cannot be viewed irrespectively of whole body composition.

Refill Adherence in Relation to Substitution and the Use of Multiple Medications: A Nationwide Population Based Study on New ACE-Inhibitor Users.

ObjectiveGeneric substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden.Study Design and SettingNew users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance.ResultsThe study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis.ConclusionThe results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications.

Dynamics of the main parameters of structure-functional condition of the left ventricle myocardium in usage of combination antihypertension therapy for postmenopausal women with different obesity patterns

Aim. To assess the dynamics of the main structural and functional parameters of the left ventricle myocardium condition (LV) in postmenopausal women with arterial hypertension (AH) and different types of obesity: abdominal (AO) and gluteofemoral (GFO), taking combination hypotensive therapy: angiotensin-converting enzyme inhibitor (ACEi) or direct renin inhibitor (DRI). Material and methods. Totally, 168 women studied with AH in postmenopause: 97 with AO and 71 with GFO. Women with different obesity types were randomized to therapy groups as ACEi+diuretic and DRI+diuretic. Follow-up lasted for 24 weeks. Results. Combination therapy that included DRI, led to target values of BP in 90,2% of patients with AO and 90,9% with GFO. Usage of DRI in AO and GFO was followed by significant decrease of wall thickness, left ventricle myocardium mass (MMLV) — by 22,6% and 17,9%, MMLV index — by 23,1% and 18,8%, respectively, (р<0,05), and parameters of diastolic function of LV. On therapy by ACEi+diuretic target values of BP were recorded in 71,4% of AO patients, and in 84,4% with GFO. In 24 weeks of ACEi usage with diuretic in AO and GFO, there was significant change of diastolic LV function (p<0,05). Comparative analysis showed that DRI therapy was better comparing to ACEi in AO patients with AO in the sense of the LV structural-functional improvement. Conclusion. Usage of ACEi or DRI in combination with diuretic in postmenopause led to significant cardioprotection not depending on obesity type. In addition, in AO the usage of DRI+diuretic was advantageous comparing to ACEi+diuretic in the sense of hypertrophy regression and LV diastolic function improvement.

Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study.

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.

Comparing the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal function decline in diabetes.

To compare effectiveness of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) for protecting Type 2 diabetes mellitus (DM2) patients from renal function decline in a real-world setting. Retrospective cohort study of new ACEi/ARB users in 2007-2012 in an unselected primary care DM2 population. Outcome is decline in renal function stage (combining estimated glomerular filtration rate and albuminuria). Patients were matched on a propensity score. Extended Cox models with time-varying covariates were used to estimate hazard ratios of outcome. The time to renal function decline for ARB users was slightly, but not significantly longer than for ACEi users (hazard ratio: 0.80; 95% CI: 0.58-1.10; p = 0.166). This study did not show significant differences between the classes in preventing renal function decline in DM2 patients in primary care.

Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome

The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics. Out of 203 patients (58 females, mean age 73.2years), 53 (26%) patients were on ACE inhibitors before their presentation with cSDH. Median initial hematoma volume in individuals with ACE inhibitors (179.2±standard error of the mean [SEM] 13.0ml) was significantly higher compared to patients without ACE inhibitors (140.4±SEM 6.2ml; p=0.007). There was an increased probability of surgical reintervention in the ACE inhibitor group (12/53, 23% versus 19/153, 12%; p=0.079), especially in patients older than 80years (6/23, 26% versus 3/45, 7%; p=0.026). ACE inhibitors are associated with higher hematoma volume in patients with cSDH and with a higher frequency of recurrences requiring surgery (especially in the very old). We hypothesize that these effects are due to ACE inhibitor induced bradykinin elevation causing increased vascular permeability of the highly vascularized neomembranes in cSDH.

Antihypertensive Drugs and Diabetic Retinopathy in Patients with Type 2 Diabetes

Objective: To evaluate the association between the development of sight-threatening diabetic retinopathy (STDR) and antihypertensive drugs (AHDs) use among type 2 diabetic patients with concomitant hypertension. Methods: Type 2 diabetic patients aged 20-100 years who had at least one prescription for AHDs between 2000 and 2011 were identified from the Longitudinal Health Insurance Database (LHID) 2005. The incidence rates of STDR were followed and Cox proportional hazard models were used to analyze the risk associated with AHDs. Results: Users of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were associated with a significantly higher risk than users of calcium channel blockers (CCBs), independent of baseline characteristics. After adjusting for time-varying use of concomitant medications for propensity score-matched or -unmatched cohorts, the results showed that patients receiving ACEIs/ARBs and CCBs were associated with a significantly greater risk compared with β-blocker users. Conclusions: Our study did not support a superiority of ACEIs/ARBs and CCBs over β-blockers for lowering the progression of diabetic retinopathy.

Renin-angiotensin-aldosterone-system inhibition is safe in the preoperative period surrounding carotid endarterectomy

Discontinuation of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) medications before surgery has been suggested because of the potentially deleterious effects of hypotension. We investigated the effect of preoperative ACEI and/or ARB use on early outcomes after carotid endarterectomy (CEA). We examined 3752 consecutive CEA patients within the Vascular Study Group of New England from September 2012 to September 2014 and compared outcomes for patients treated (n = 1772) or not treated (n = 1980) with ACEI and/or ARB preoperatively. Outcomes included perioperative need for intravenous vasoactive medication (IVBPmed) for hypotension or hypertension (HTN), major adverse cardiac events (MACEs), and the combined outcome of stroke or death. Adjusted analysis was performed using multivariable logistic regression of the crude cohort and by constructing a propensity score matched cohort (n = 1441). ACEI and/or ARB users were more likely to be male (64% vs 59%; P = .001), with a higher prevalence of diabetes (41% vs 28%; P < .0001), HTN (97% vs 82%; P < .0001), coronary artery disease (31% vs 25%; P = .0001), congestive heart failure (10% vs 8%; P = .02), and asymptomatic carotid disease (59% vs 54%; P = .004). Patients who received ACEI and/or ARB preoperatively were more likely to be treated with aspirin (92% vs 88%; P = .0002) and statins (89% vs 85%; P = .001) preoperatively. In the unadjusted analysis, no significant differences were identified in hypotension that required IVBPmed (12% vs 11%; odds ratio [OR], 1.1; 95% confidence interval [CI], 0.9-1.4; P = .22), MACE (3% vs 2%; OR, 1.3; 95% CI, 0.8-1.9; P = .32), or stroke or death (3% vs 3%; OR, 1.0; 95% CI, 0.7-1.6; P = .89) for preoperative ACEI and/or ARB treated and nontreated patients, respectively. Preoperative ACEI and/or ARB usage was, however, associated with HTN that required IVBPmed (13% vs 10%; OR, 1.3; 95% CI, 1.1-1.6; P = .01). Analysis of the propensity score matched cohort revealed no significant differences in hypotension that required IVBPmed (12% vs 12%; OR, 1.0; 95% CI, 0.8-1.3; P = .86), MACE (3% vs 2%; OR, 1.1; 95% CI, 0.7-1.8; P = .62; ), or stroke or death (3% vs 3%; OR, 1.0; 95% CI, 0.7-1.6; P = .91) for patients treated or not treated with preoperative ACEI and/or ARB, respectively. ACEI and/or ARB remained associated with HTN that required IVBPmed (13% vs 10%; OR, 1.3; 95% CI, 1.0-1.7; P = .02). Results were similar after adjustment using logistic regression. The incidence of hospital length of stay >1 day was similar between ACEI and/or ARB treated and not treated patients (29% vs 32%; OR, 0.9; 95% CI, 0.8-1.1; P = .21). Preoperative ACEI and/or ARB use was associated with marginally increased use of IVBPmed for HTN but not for hypotension and was not associated with increased MACE, stroke, or death. On the basis of these metrics, the use of preoperative ACEI and/or ARB appears safe before CEA.

Preadmission use of renin-angiotensin blockers and rupture of abdominal aortic aneurysm: a nationwide, population-based study.

Rupture of abdominal aortic aneurysms (rAAA) is associated with high mortality. Use of angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs) has been suggested to reduce the risk of rAAA. This nationwide, combined case-control and follow-up study aims to examine the possible impact of preadmission renin-angiotensin system blockade on the risk of rAAA and case fatality following rAAA. Using Danish healthcare registries, a combined case-control and follow-up study was conducted among all patients with a first-time hospital admission for rAAA and AAA controls without rupture in Denmark from 1996 to 2012. Individual-level data were obtained on preadmission drug use, comorbidity, socioeconomic factors, healthcare services use, and death. The adjusted age-matched and sex-matched odds ratios (adj. OR) were 0.96 (95% confidence interval (CI): 0.85; 1.07) for rAAA for current ACE-inhibitor users and 0.93 (95%CI: 0.79; 1.09) for current ARB users compared with never users. Propensity score-matched analyses yielded similar results for current ACE-inhibitor users (adj. OR: 1.02, 95%CI: 0.88; 1.19) and current ARB users (adj. OR: 1.02, 95%CI: 0.83; 1.26). The total 30-day mortality rate after hospital admission was 61.0% in current ACE-inhibitor users compared with 59.4% in non-ACE-inhibitor users (adjusted mortality rate ratio (adj. MRR) 1.06, 95%CI: 0.94; 1.20) and 58.6% in current ARB users compared with 59.9% in non-ARB users (adj. MRR: 0.96, 95%CI: 0.82; 1.14). Use of renin-angiotensin system blockade was not associated with a lower risk of rAAA or lower case fatality following rAAA.

Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study.

We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. Thiazide users had a slower decline in BMD compared to nonusers, while decline among ACE inhibitor and beta blocker users were similar to rates in nonusers. Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women's Health Across the Nation. We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14 years of observation were compared with nonusers. Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of nonusers. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (-0.28% vs -0.88%; p = 0.008) and the spine (-0.74% vs -1.0%; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in nonusers. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (-0.35% vs -0.60%; p = 0.08) and a similar trend at the FN (-0.39% vs -0.64%; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (-0.48% vs -0.82%; p = 0.02), but not at the spine (-0.40% vs -0.56%; p = 0.23). Neither ACEi nor BB was associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with nonusers, as well as compared with ACEi and BB.

Angiotensin II Blockade Is Associated With Worse Clinical Outcomes in IBD Patients

Introduction: Preclinical data support the notion that activation of the renin-angiotensin system (RAS) contributes to the pathogenesis of inflammatory bowel disease (IBD), and inhibition of RAS by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) protects against colitis in animal models. Less is known regarding clinical outcomes with use of these medications in IBD patients. In order to test the hypothesis that blockade of RAS improves intestinal inflammation, we compared clinical outcomes in ACEI or ARB treated individuals to matched untreated patients in a cohort of IBD patients from a single tertiary care center. Methods: We performed a retrospective cohort study using the IBD registry at the University of Chicago. ACEI or ARB users were compared to non-users matched 1:4 on the basis of sex, age +/- 5 years, diagnosis, and disease location. Data on clinical outcomes including rates of hospitalizations, operations, and corticosteroid use were collected in addition to comorbidities and medication use. Results: Sixty-five ACEI- or ARB-treated patients with a minimum of six months of follow up were included, 41 patients with Crohn's disease (CD) and 24 with ulcerative colitis (UC) with mean follow up of 2.3 years. The control group was comprised of 260 matched IBD patients with no history of ACEI or ARB exposure with mean follow up of 2.9 years. Mean age was 53 years in the ACEI/ARB group and 52 years in the control group. Thiopurine, anti-TNFα, and 5-ASA medications were similar between the two groups. Compared to control patients, CD patients taking ACEI or ARB had higher rates of hospitalizations per year (0.45 v. 0.21), similar numbers of operations per year (0.17 v. 0.16), and more corticosteroid prescriptions per year (0.70 v. 0.61). UC patients taking ACEI or ARB had more hospitalizations per year (0.35 v. 0.11), more operations per year (0.16 v. 0.08), and more corticosteroid prescriptions per year (1.22 v. 0.34) compared to control patients. ACEI use was also associated with increased hospitalization rates and operations compared to ARB use among IBD patients (0.45 v. 0.34 and 0.19 v. 0.14, respectively), but a lower number of corticosteroid prescriptions per year (0.68 v. 1.30). Conclusion: ACEI or ARB use in IBD patients was associated with more hospitalizations, operations, and corticosteroid use in our tertiary referral population. Prospective studies are needed to assess the causal role of RAS inhibition on disease activity.

Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks Versus Whites

BackgroundClinical trial evidence suggests poorer outcomes in blacks compared with whites when treated with an angiotensin-converting enzyme (ACE) inhibitor–based regimen, but this has not been evaluated in clinical practice. ObjectivesThis study evaluated the comparative effectiveness of an ACE inhibitor–based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared with whites. MethodsWe conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models. ResultsOur analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05), and congestive heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group. ConclusionsACE inhibitor–based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor–based regimen.

Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on major adverse cardiac events in patients with newly diagnosed type 2 diabetes: A nationwide study

BackgroundGuidelines for hypertension management recommend either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) as first-line therapies for diabetes population. No head-to-head trial has been conducted to determine the priority of ACEI/ARB use for major adverse cardiac events (MACEs) in diabetes mellitus. MethodsData on patients with newly diagnosed diabetes treated with ACEIs or ARBs were collected from Taiwan's National Health Insurance Research Database for the period 2000–2010. A total of 30,777 ARB users and 21,436 ACEI users were identified. One ARB user was matched to one ACEI user by propensity score. Intention-to-treat (ITT) and as-treated (AT) models were used. The primary outcomes were myocardial infarction, ischemic stroke, and all-cause mortality. The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. FindingsCompared with ACEI users (n=21,436), ARB users (n=30,777) showed no significant difference in the outcomes of myocardial infarction (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.80 to 1.07), ischemic stroke (HR: 0.95; 95% CI: 0.87 to 1.04), or all-cause mortality (HR: 0.95; 95% CI: 0.89 to 1.01) in the ITT analysis. The risks of hospitalization for acute kidney injury and hyperkalemia also did not differ between groups. ACEI and ARB use also had similar effects on MACEs and adverse effects in the AT analysis. ConclusionsThis large cohort study supports the comparative effectiveness of ACEIs and ARBs in terms of MACE outcomes in patients with incident diabetes.

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

PurposeAlthough angiotensin-converting enzyme (ACE) inhibitor use during conventionally fractionated radiation therapy has been associated with a decreased risk of radiation pneumonitis (RP), a similar effect has not been demonstrated in stereotactic body radiation therapy (SBRT). The purpose of this study was to examine the impact of ACE inhibitor use during SBRT on the risk of symptomatic (grade ≥2) RP. Methods and materialsPatients with at least 1 follow-up treated with SBRT for primary lung cancer were included. ACE inhibitors, angiotensin receptor blockers, statins, nonsteroidal anti-inflammatory drugs, and glucocorticoids were examined. RP was determined from all available medical records, including follow-up appointments with radiation oncology, pulmonology, medical oncology, and hospitalizations. It was scored with the Common Terminology Criteria for Adverse Events, version 4.0. Analysis was performed with Kaplan-Meier and Cox proportional hazards modeling. ResultsA total of 257 patients met inclusion criteria. Seventy (27.2%) used an ACE inhibitor during SBRT. The overall rates of grade ≥2 and ≥3 RP were 19.1% (n = 49) and 7.0% (n = 18), respectively. ACE inhibitor users experienced greater freedom from symptomatic RP on univariate (vs nonusers, 89.8% vs 76.3% at 12 months, P = .029) and multivariate analysis (hazard ratio 0.373, 95% confidence interval 0.156-0.891, P =.026). The volume of normal lung tissue receiving ≥5 Gy, %, ≥10 Gy, ≥20 Gy, and mean lung dose were also significantly associated with RP on univariate and multivariate analysis. ACE inhibitor use was not associated with overall survival. Angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, glucocorticoids, and statin administration were not associated with symptomatic RP or survival. ConclusionsACE inhibitor use during SBRT was associated with significantly greater freedom from grade ≥2 RP, even after adjusting for pulmonary dose. Given the data on their protective effect in human and animal models, a prospective evaluation is warranted.