Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.
ABSTRACT: BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.
Project description:AIMS:The aim was to assess the impact of a campaign for general practitioners (GPs) to reduce clinically-important drug-drug interactions (DDIs) in poly-treated elderly patients. METHODS:We compiled a list of 53 DDIs and analyzed reimbursed prescriptions dispensed to poly-treated (?four drugs) elderly (>65 years) patients in the Emilia Romagna region during January 2011-June 2011 (first pre-intervention period), January 2012-June 2012 (second pre-intervention period) and January 2013-June 2013 (post-intervention period). Educational initiatives to GPs were completed in July 2012-December 2012. Pre-test/post-test analysis (2013 vs. 2012) was performed, also using predicted 2013 data (P < 0.01 for statistical significance). RESULTS:Despite the slight increase in poly-therapy rate (16% in 2013, +1.5% from 2011), we found a stable or slightly declining number of potential DDIs for each elderly poly-treated patient (~1.5). In 2013, 11 DDIs exceeded 5% of prevalence rate: antidiabetics-?-adrenoceptor blockers ranked first (20.3%), followed by ACE Inhibitors (ACEIs)/sartans-non steroidal anti-inflammatory drugs (NSAIDs) (16.4%), diuretics-NSAIDs (13.6%), selective serotonin re-uptake inhibitors (SSRIs)-NSAIDs/acetyl salicylic acid (ASA) (12.7%) and corticosteroids-NSAIDs/ASA (9.7%). A remarkable reduction emerged for NSAID-related DDIs (diuretics-NSAIDs peaked -14.5%; P < 0.01), whereas prevalence of antidiabetics-?-adrenoceptor blockers increased (+7.9%; P < 0.01). When using predicted values, the statistical significance disappeared for antidiabetics-?-adrenoceptor blockers (+1.3%; P = 0.04), whereas it persisted for almost all NSAIDs-related DDIs: ACEIs/sartans-NSAIDs (-3.0%), diuretics-NSAIDs (-6.0%), SSRIs-NSAIDs/ASA (-5.9%). CONCLUSIONS:This campaign contained the burden of DDIs in poly-treated elderly patients by 1) reducing most prevalent DDIs, especially NSAIDs-related DDIs and 2) balancing the observed rise in poly-therapy rate with stable rate in overall prescriptions of potentially interacting drugs per patient.
Project description:Background:Nonsteroidal anti-inflammatory drugs (NSAIDS) are increasingly important alternatives to opioids for analgesia during hospitalization as health systems implement opioid-minimization initiatives. Increasing NSAID use may increase AKI rates, particularly in patients with predisposing risk factors. Inconclusive data in outpatient populations suggests that NSAID nephrotoxicity is magnified by renin-angiotensin system inhibitors (RAS-I). No studies have tested this in hospitalized patients. Methods:Retrospective, active-comparator cohort study of patients admitted to four hospitals in Philadelphia, Pennsylvania. To minimize confounding by indication, NSAIDs were compared to oxycodone, and RAS-I were compared to amlodipine. We tested synergistic NSAID+RAS-I nephrotoxicity by comparing the difference in AKI rate between NSAID versus oxycodone in patients treated with RAS-I to the difference in AKI rate between NSAID versus oxycodone in patients treated with amlodipine. In a secondary analysis, we restricted the cohort to patients with baseline diuretic treatment. AKI rates were adjusted for 71 baseline characteristics with inverse probability of treatment-weighted Poisson regression. Results:The analysis included 25,571 patients who received a median of 2.4 days of analgesia. The overall AKI rate was 23.6 per 1000 days. The rate difference (RD) for NSAID versus oxycodone in patients treated with amlodipine was 4.1 per 1000 days (95% CI, -2.8 to 11.1), and the rate difference for NSAID versus oxycodone in patients treated with RAS-I was 5.9 per 1000 days (95% CI, 1.9 to 10.1), resulting in a nonsignificant interaction estimate: 1.85 excess AKI events per 1000 days (95% CI, -6.23 to 9.92). Analysis in patients treated with diuretics produced a higher, albeit nonsignificant, interaction estimate: 9.89 excess AKI events per 1000 days (95% CI, -5.04 to 24.83). Conclusions:Synergistic nephrotoxicity was not observed with short-term NSAID+RAS-I treatment in the absence of concomitant diuretics, suggesting that RAS-I treatment may not be a reason to choose opioids in lieu of NSAIDs in this population. Synergistic nephrotoxicity cannot be ruled out in patients treated with diuretics.
Project description:We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696-0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775-0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.
Project description:Although acute kidney injury (AKI) is well studied in the acute care setting, investigation of AKI in the nursing home (NH) setting is virtually nonexistent. The goal of this study was to determine the incidence of drug-associated AKI using the RIFLE (Risk, Injury, Failure, Loss of kidney function, or End-Stage kidney disease) criteria in NH residents.We conducted a retrospective study between February 9, 2012, and February 8, 2013, for all residents at 4 UPMC NHs located in southwest Pennsylvania. The TheraDoc™ Clinical Surveillance Software System, which monitors laboratory and medication data and fires alerts when patients have a sufficient increase in serum creatinine, was used for automated case detection. An increase in serum creatinine in the presence of an active medication order identified to potentially cause AKI triggered an alert, and drug-associated AKI was staged according to the RIFLE criteria. Data were analyzed by frequency and distribution of alert type by risk, injury, and failure.Of the 249 residents who had a drug-associated AKI alert fire, 170 (68.3%) were women, and the mean age was 74.2 years. Using the total number of alerts (n = 668), the rate of drug-associated AKI was 0.41 events per 100 resident-days. Based on the RIFLE criteria, there were 191, 70, and 44 residents who were classified as AKI risk, injury, and failure, respectively. The most common medication classes included in the AKI alerts were diuretics, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs), and antibiotics.Drug-associated AKI was a common cause of potential adverse drug events. The vast majority of cases were related to the use of diuretics, ACEIs/ARBs, and antibiotics. Future studies are needed to better understand patient, provider, and facility risk factors, as well as strategies to enhance the detection and management of drug-associated AKI in the NH.
Project description:<h4>Background</h4>The advantages of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular events (CVEs) and delaying end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) is well-known. However, the efficacy and safety of these agents in non-dialysis CKD stages 3-5 patients are still a controversial issue.<h4>Methods</h4>Two investigators (Yaru Zhang and Dandan He) independently searched and identified relevant studies from MEDLINE (from 1950 to October 2018), EMBASE (from 1970 to October 2018), and the Cochrane Library database. Randomised clinical trials in non-dialysis CKD3-5 patients treated with renin-angiotensin system (RAS) inhibitors were included. We used standard criteria (Cochrane risk of bias tool) to assess the inherent risk of bias of trials. We calculated the odds ratio (OR) and 95% confidence interval (CI) for each outcome by random-effects model. A 2-sided p value <?0.05 was considered statistically significant, and all statistical analyses were performed using STATA, version 15.0. This network meta-analysis was undertaken by the frequency model.<h4>Results</h4>Forty-four randomised clinical trials with 42,319 patients were included in our network meta-analysis. ACEIs monotherapy significantly decreased the odds of kidney events (OR 0.54, 95% CI 0.41-0.73), cardiovascular events (OR 0.73, 95% CI 0.64-0.84), cardiovascular death (OR 0.73, 95% CI 0.63-0.86) and all-cause death (OR 0.77, 95% CI 0.66-0.91) when compared to placebo. According to the cumulative ranking area (SUCRA), ACEI monotherapy had the highest probabilities of their protective effects on outcomes of kidney events (SUCRA 93.3%), cardiovascular events (SUCRA 77.2%), cardiovascular death (SUCRA 86%), and all-cause death (SUCRA 94.1%), even if there were no significant differences between ACEIs and other antihypertensive drugs, including calcium channel blockers (CCBs), ?-blockers and diuretics on above outcomes except for kidney events. ARB monotherapy and combination therapy of an ACEI plus an ARB showed no more advantage than CCBs, ?-blockers and diuretics in all primary outcomes. In the subgroup of non-dialysis diabetic kidney disease patients, no drugs, including ACEIs or ARBs, significantly lowered the odds of cardiovascular events and all-cause death. However, ACEIs were still better than other antihypertensive drugs including ARBs in all-cause death but not ARBs in cardiovascular events according to the SUCRA. Only ARBs had significant differences in preventing the occurrence of kidney events compared with placebo (OR 0.82, 95% CI 0.72-0.95). Both ACEI/ARB monotherapy and combination therapy had higher odds of hyperkalaemia. ACEIs had 3.81 times higher odds than CCBs (95% CI 1.58-9.20), ARBs had 2.08-5.10 times higher odds than placebo and CCBs and combination therapy of an ACEI and an ARB had 4.80-24.5 times higher odds than all other treatments. Compared with placebo, CCBs and ? blockers, ACEI therapy significantly increased the odds of cough (OR 2.90, 95% CI 1.76-4.77; OR 8.21, 95% CI 3.13-21.54 and OR 1.80, 95% CI 1.08-3.00). There were no statistical differences in hypotension among all comparisons except ACEIs versus placebo.<h4>Conclusions</h4>Although ACEIs increased the odds of hyperkalaemia, cough and hypotension, they were still superior to ARBs and other antihypertensive drugs and had the highest benefits for the prevention of kidney events, cardiovascular outcomes, cardiovascular death and all-cause mortality in non-dialysis CKD3-5 patients. In patients with advanced diabetic kidney disease, ACEIs were superior to ARBs in lowering risk of all-cause death but not in kidney events and cardiovascular events.
Project description:Background:In peritoneal dialysis (PD) patients, whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could protect residual renal function is still controversial. To assess the effects of ACEIs and ARBs on the residual renal function and cardiovascular (CV) events in peritoneal dialysis patients, we performed a meta-analysis of randomized controlled trials. Materials and Methods:We searched PubMed, EMBASE, the Cochrane Library, the CNKI database, and the Wanfang database for relevant articles from database inception to November 30, 2019. Randomized controlled trials were included. The primary outcome was the decline in the residual renal function (RRF). Results:Thirteen trials with 625 participants were included in the meta-analysis. The average residual GFR declined by 1.79?ml/min per 1.73?m2 in the ACEI/ARB group versus 1.44?ml/min per 1.73?m2 in the placebo or active control group at 3 mo. The average residual GFR declined by 2.02 versus 2.06, 2.16 versus 2.72, and -0.04 versus 2.74?ml/min per 1.73?m2 in the placebo or active control group at 6 months (mo), 12 mo, and 24 mo, respectively. The decline in residual GFR showed a significant difference between the ACEI/ARB group and the placebo or active control group at 12 mo (MD = -0.64?ml/min?per?1.73?m2; 95% CI: -0.97~-0.32; I 2 = 44%; P < 0.0001). No significant difference was observed in Kt/V, urinary protein excretion, weekly creatinine clearance, CV events, or serum potassium levels. Conclusions:In the present study, we found that the use of ACEIs and ARBs, especially long-term treatment, decreased the decline of RRF in patients on PD. ACEIs and ARBs do not cause an additional risk of side effects.
Project description:Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP) and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost savings due to high adherence.
Project description:Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025. Treatment remains suboptimal, with control of blood pressure achieved in only 20%-35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals. To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) are combined with calcium channel blockers (CCBs) and/or thiazide diuretics. The rationale for this strategy is based, in part, on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy. Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ). Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs. Among the different ARBs, olmesartan medoxomil is available as a dual fixed-dose combination with either amlodipine or HCTZ, and the increased blood pressure-lowering efficacy of these two combinations is proven. Triple therapy is required in 15%-20% of treated uncontrolled hypertensive patients, with a renin-angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines. Olmesartan, amlodipine, and HCTZ are available as a triple fixed-dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations. The availability of these fixed-dose combinations should lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition.
Project description:BACKGROUND:The association of antihypertensive drugs with the risk and severity of COVID-19 remains unknown. METHODS AND RESULTS:We systematically searched PubMed, MEDLINE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and medRxiv for publications before July 13, 2020. Cohort studies and case-control studies that contain information on the association of antihypertensive agents including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCBs), ?-blockers, and diuretics with the risk and severity of COVID-19 were selected. The random or fixed-effects models were used to pool the odds ratio (OR) with 95% confidence interval (CI) for the outcomes. The literature search yielded 53 studies that satisfied our inclusion criteria, which comprised 39 cohort studies and 14 case-control studies. These studies included a total of 2,100,587 participants. We observed no association between prior usage of antihypertensive medications including ACEIs/ARBs, CCBs, ?-blockers, or diuretics and the risk and severity of COVID-19. Additionally, when only hypertensive patients were included, the severity and mortality were lower with prior usage of ACEIs/ARBs (overall OR of 0.81, 95% CI 0.66-0.99, p < 0.05 and overall OR of 0.77, 95% CI 0.66-0.91, p < 0.01). CONCLUSIONS:Taken together, usage of antihypertensive drugs is not associated with the risk and severity of COVID-19. Based on the current available literature, it is not recommended to abstain from the usage of these drugs in COVID-19 patients. REGISTRATION:The meta-analysis was registered on OSF (https://osf.io/ynd5g).
Project description:<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> Patients taking ACEIs had a lower risk of developing radiation pneumonitis compared with non-users (OR = 0.46, 95%CI = 0.31-0.67, <i>p</i> < 0.0001). While the use of ARBs couldn't reduce the incidence of RP (OR = 1.42, 95%CI = 0.94-2.14, <i>p</i> = 0.10). Elderly patients (age ? 70) benefited more from ACEIs (OR = 0.12, 95%CI = 0.02-0.67, <i>p</i> = 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, <i>p</i> = 0.005), but sex and the use of statin or NSAID had no influence on the appearance of RP (<i>p</i> = 0.59, <i>p</i> = 0.70, <i>p</i> = 0.40, respectively). <b>Conclusions:</b> 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.