Adverse clinical events in Japanese atrial fibrillation patients with and without coronary artery disease—findings from the SAKURA AF Registry

Abstract

Background: Although atrial fibrillation (AF) and coronary artery disease (CAD) are increasing in prevalence in Japan, real-world data regarding clinical outcomes in Japanese AF patients with CAD are limited.

Methods: The SAKURA AF Registry is a prospective multi-center registry created to investigate outcomes of oral anticoagulant (OAC) use in Japanese AF patients. A study was conducted involving 3237 enrollees from 63 Tokyo-area institutions who were followed up for a median of 39.3?months. Clinical adverse events were compared between the patients accompanied with (n?=?312) and without CAD (n?=?2925).

Results: The incidence of cardiovascular events and all-cause mortality rates were significantly higher among patients with CAD than among those without CAD (5.98 vs 2.52 events per 100 patient-years, respectively, p?<?0.001; 3.27 vs 1.94 deaths per 100 patient-years, respectively, p?=?0.012), but there was no difference in strokes/transient ischemic attacks or systemic embolisms (1.70 vs 1.34). After a multivariate adjustment, CAD remained a risk factor for cardiovascular events (hazard ratio [HR]?=?1.57, 95% confidence interval [CI]?=?1.08–2.25, p?=?0.018). Among CAD patients, the propensity score-adjusted risk for major bleeding was significantly decreased among direct oral anticoagulant (DOAC) users in comparison to that among warfarin users (HR?=?0.29, 95% CI?=?0.07–0.94, p?=?0.04), but other adverse clinical events did not differ significantly between these two groups.

Conclusions: CAD did not appear to be a major determinant of strokes/TIAs, major bleeding, or all-cause mortality, but appeared to increase the risk of cardiovascular events in Japanese AF patients. The risk of major bleeding in CAD patients appeared to decrease when a DOAC rather than warfarin was administered. The data suggested that patients with AF and concomitant CAD require careful management and follow-up to reduce cardiovascular risks, and DOACs may be a better choice over warfarin when considering the risk of major bleeding.     

Safety,effectiveness, and health care cost comparisons among elderly patients with venous thromboembolism prescribed warfarin or apixaban in the United States Medicare population

Abstract

Objective: To compare safety, effectiveness, and healthcare costs of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, recurrent venous thromboembolism (VTE), and all-cause hospitalization among elderly Medicare VTE patients prescribed warfarin vs apixaban.

Methods: Using 100% Medicare data, elderly patients prescribed apixaban or warfarin within 30 days after a VTE encounter were identified. Patients had continuous health plan enrollment and no parenteral or oral anticoagulant use ≤6 months preceding the VTE encounter. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazard models were used to assess the risk of MB, CRNM bleeding, recurrent VTE, and all-cause hospitalization. Generalized linear and two-part models were used to estimate MB-, recurrent VTE-, and all-cause related costs (per patient per month [PPPM]).

Results: In the pre-matched cohort, 25,284 (66.9%) patients were prescribed warfarin and 12,515 (33.1%) apixaban. After 1:1 PSM, 11,363 matched pairs of apixaban-warfarin patients were included for a mean follow-up of 4.0 and 4.4 months, respectively. Matched cohorts had a mean age of 78 years and mean Charlson Comorbidity Index score of 2.9. Warfarin was associated with a higher risk of MB (hazard ratio [HR]?=?1.31; 95% confidence interval [CI]?=?1.10–1.57) and CRNM bleeding (HR?=?1.31; 95% CI?=?1.19–1.43) vs apixaban. The risks of recurrent VTE (HR?=?0.96; 95% CI?=?0.70–1.33) and all-cause hospitalization (HR?=?1.05; 95% CI?=?0.99–1.12) were similar among warfarin and apixaban patients. Warfarin patients had higher MB-related ($147 vs $75; p?=?.003) and all-cause costs PPPM ($3,267 vs $3,033; p?<?.001), but similar recurrent VTE-related medical costs PPPM ($30 vs $36; p?=?.516) vs apixaban patients.

Conclusions: Warfarin was associated with significantly higher risk of MB and CRNM bleeding as well as higher MB-related and all-cause costs vs apixaban patients. Recurrent VTE risk and costs were similar among warfarin and apixaban patients.     

长期使用华法林抗凝的非瓣膜性房颤患者围手术/操作期使用NOAC桥接的抗凝方案研究

目的：探讨使用非维生素K拮抗剂的口服抗凝药物（NOAC）代替肝素类药物在围手术/操作期患者进行桥接抗凝的可行性。方法：本研究为前瞻性观察研究,2018年8月至2021年5月入选长期使用华法林抗凝的非瓣膜性房颤患者,观察患者在围手术/操作期使用NOAC桥接抗凝后,围手术/操作期以及术后30天内栓塞事件与出血事件的发生率。结果：共入选患者21例,其中4例行肠镜检查,3例行胃镜检查,8例行拔牙操作,3例行眼科相关操作,3例行皮肤科相关操作。患者的平均年龄（70.8±8.5）岁,女性有9例,平均CHA2DS2-VASc评分（3.0±1.0）分,平均HAS-BLED评分（1.4±0.7）分。21例术后30天均未出现出血事件与栓塞事件。结论：对于非瓣膜性房颤患者,采取NOAC在围手术/操作期进行桥接抗凝,具有一定的可行性。     

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Abstract

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.

Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6?years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.

Results: The study included 2494 patients (age = 76.0?±?9.5?years, CHA₂DS₂-VASc = 4.0?±?1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1?±?10.3 years), with better kidney function (mean CrCl = 80.6?±?35.8?ml/min) and lower CHA₂DS₂-VASc (3.7?±?1.4) and HAS-BLED (2.1?±?0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3?±?1.6 and 2.6?±?0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p?<?.001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.

Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).     

Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

心房颤动采用三联疗法和双重抗血小板疗法抗血栓治疗策略对卒中、主要不良心脑血管事件、出血事件、全因病死率影响的Meta分析

目的 综合评价三联疗法(TT)和双重抗血小板治疗(DAPT)的策略在心房颤动(AF)病人接受经皮冠状动脉介入治疗(PCI)后对卒中、主要不良心脑血管事件(MCAE)、出血事件、全因病死率的影响.方法 检索PubMed,Embase,Web of Science数据库中2000―2018年的文章.根据纳入和排除标准进行筛...     

住院心房颤动患者抗凝治疗现状分析

目的了解住院心房颤动（房颤）患者抗凝治疗中存在的问题,为更加安全的抗凝治疗提供依据。方法收集2013年1月1日至8月31日在江苏省苏北人民医院心内科住院治疗的所有非瓣膜性房颤患者病历资料进行回顾性分析。根据2010年《欧洲心脏病学会（ESC）心房颤动治疗指南》,采用CHADS2-VASc评分和HAS—BLED评分分别对患者进行血栓栓塞危险程度分层和出血风险评估。主要分析指标为接受不同房颤治疗方案（室率控制,节律控制）患者的血栓栓塞危险分层,出血风险评分,抗凝药物应用情况、国际标准化比值（INR）、出血合并症、血栓栓塞事件、患者用药依从性等。结果纳入分析的患者共134例,男性69例,女性67例;年龄20～91岁,平均（67±14）岁,CHA2DS2-VASe评分为0、1和≥2分者分别为11、23和100例,HAS—BELD评分≥3分者13例。接受室率控制和节律控制治疗者分别为85和49例。接受室率控制治疗的85例患者中CHA2DS2-VASe评分为0、1、≥2分者分别为1、12、72例。0分者1例使用阿司匹林。1分者12例中2例应用华法林,2例未行抗凝治疗（1例有禁忌证）,8例使用抗血小板药物（阿司匹林、氯吡格雷单用或二药联用）,其中2例单用氯吡格雷患者头颅CT检查均有多发性缺血灶。≥2分者72例中33例应用华法林,35例应用抗血小板药物,4例未行抗凝治疗。接受华法林抗凝治疗的患者出院时25例INR〈2．0,7例INR为2．0～3．0,1例INR〉3．0。接受节律控制治疗的49例患者CHA2DS2-VASe评分平均为（2．3±1．8）,HAS—BLED评分平均为（1．3±1．1）,其中25例应用华法林,出院时17例INR〈2．0,5例INR为2．0～3．0,2例INR〉3．0。1例患者未监测INR。134例患者中有15例（11．2％）出现脑梗死,其中8例（53．3％）应用华法林抗凝治疗,患者出院时INR均未达标。结论住院房颤患者抗凝治疗中存在的主要问题是采用华法林抗凝的比例较低,采用华法林治疗的部分患者抗凝强度不足。临床医师过分担心发生出血合并症是抗凝治疗不规范的主要原因。     

某三甲医院心房颤动患者华法林规范化抗凝治疗现状调查分析

目的：了解心房颤动患者抗凝治疗现状,为心房颤动规范化抗凝治疗提供参考。方法：选取皖南医学院弋矶山医院2013年1月~2014年12月非瓣膜性心房颤动患者200例,采用CHA2DS2-VASc和HAS-BLED评分系统对纳入人群进行血栓危险分层和出血风险评估,并依据《2010年欧洲心脏病学会（ESC）心房颤动治疗指南》评价其规范化抗凝情况。结果：CHA2DS2-VASc和HAS-BLED评分分别为（2.73±2.10）分和（1.57±1.13）分。183例（91.5%）患者接受抗血栓治疗,使用华法林抗凝治疗的有74例（37%）,而血栓高危组125例患者中,接受华法林抗凝治疗50例（40%）。华法林抗凝治疗时间（5.78±4.73） d,累积给药剂量为（19.46±18.19） mg,55例（74.32%）患者出院前监测国际标准化比值（INR）,INR达标率为30.9%。结论：心房颤动以华法林抗凝治疗现状不容乐观,应采取有效的干预措施,提高心房颤动患者抗凝治疗规范化程度。     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Liver Disease: A Meta-Analysis and Systematic Review

Background

The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population.

Methods

We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).

Results

A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66–0.93), major bleeding (RR 0.68, 95% CI 0.53–0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41–0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57–1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61–1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37–0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38–0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31–0.97) compared with warfarin.

Conclusions

Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease.

     

Stroke risk reduction outweighed bleeding risk increase from vitamin K antagonist treatment among nonvalvular atrial fibrillation patients with high stroke risk and low bleeding risk

Objective: Warfarin is widely used for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We compared the rates of stroke and major bleeding in NVAF patients with a high stroke risk and low bleeding risk profile during warfarin treated (W+) and warfarin untreated (W?) periods.

Method: Insurance claims from six commercial, Medicaid or Medicare databases were analyzed from 2000 to 2014. NVAF patients treated with warfarin, with a CHADS₂/CHA₂DS₂-VASc score ≥2, and an ATRIA score ≤3 at baseline were identified. Incidence rate ratios (IRRs) of stroke and major bleeding were calculated for W?+?versus W? episodes of person-time, as well as for first 30 days versus beyond 30 days of W?+?episodes.

Results: Among 316,145 patients, anticoagulant prophylaxis with warfarin significantly reduced stroke risk, with IRRs ranging from 0.48 (95% CI: 0.46–0.51) to 0.80 (95% CI: 0.70–0.91), and increased major bleeding risk, with IRRs ranging from 1.13 (95% CI: 1.10–1.15) to 1.95 (95% CI: 1.10–3.45). Stroke and major bleeding rates were higher during the first 30 days of W?+?than beyond.

Conclusion: In NVAF patients at high risk for stroke and low risk for bleeding, our data confirm the effectiveness of anticoagulation for stroke prevention. The decrease in stroke risk of anticoagulation may outweigh the risk of major bleeding events, particularly among elderly patients. Potential risks of warfarin during initiation warrant attention, especially among patients who stop and start therapy repeatedly.     

一例房颤合并冠心病患者初始抗栓治疗策略及文献复习

目的 探讨房颤伴急性冠脉综合征的抗栓治疗策略。方法 1例46岁房颤合并冠心病的男性患者,房颤卒中风险低危,入院期间未给予抗凝治疗,后出现急性脑梗塞。通过提阅部分指南及文献,分析CHA₂DS₂-VAS_c评分为1分,并伴急性冠脉综合征患者的不同抗栓治疗策略方案及其优劣。结果 文献提示,CHA₂DS₂-VAS_c评分为1分出血低危患者,建议尽早服用抗凝药。双联抗栓（华法林+氯吡格雷）能够有效抗栓并且降低患者出血风险,因此需根据患者的具体情况,尽快将三联调整为双联抗栓（1~3个月内）,保证患者疗效的情况下,降低患者出血风险。结论 临床上遇到相关患者需充分评估患者的出血及血栓风险,制定个体化的抗栓治疗策略。     

Comparative effectiveness of coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) in elderly patients with diabetes

Objective: To compare the relative effectiveness of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among elderly patients with diabetes regarding acute myocardial infarction (AMI), stroke, repeat revascularization, and all-cause mortality.

Methods: A retrospective cohort study was conducted using the 2006–2008 5% national sample of Medicare claims data. Elderly (≥65 years) beneficiaries with at least two claims of diabetes separated by ≥30 days and who had at least one inpatient claim for multi-vessel CABG or PCI between 1 July 2006 and 30 June 2008 were identified. The date of beneficiary’s first CABG or PCI was defined as the index date. All patients were followed from the index date to 31 December 2008 for outcomes. CABG and PCI patients were 1:1 matched on propensity scores and index dates. Cox proportional hazards models were used to compare postoperative outcomes between patients undergoing CABG versus PCI.

Results: The matched sample consisted of 4430 patients (2215 in each group). The Cox proportional hazards models showed that, compared to patients undergoing PCI, CABG was associated with a lower risk of postoperative AMI (hazard ratio [HR]: 0.494; 95% CI: 0.396–0.616; p?<?.0001), repeat revascularization (HR: 0.194; 95% CI: 0.149–0.252; p?<?.0001), the composite outcome (HR: 0.523; 95% CI: 0.460–0.595; p?<?.0001), and all-cause mortality (HR: 0.775; 95% CI: 0.658–0.914; p?=?.0024); postoperative risk of stroke was not significantly different between the two groups (HR: 0.965; 95% CI: 0.812–1.148; p?=?.691).

Conclusions: CABG appears to be the preferred revascularization strategy for elderly patients with diabetes and coronary heart disease. However, this result should be interpreted considering study limitations, for example, several patient clinical variables and physician-related factors which may affect procedure outcomes are not available in the data. Clinical decisions should be individualized considering all patient- and physician-related factors.     

高风险冠心病合并房颤用抗凝和双联抗栓治疗的疗效及安全性观察

目的观察冠心病合并房颤患者抗栓与抗凝治疗的疗效及安全性。方法将67例栓塞风险评分（CHADS2）为3-6分,出血风险评分（HEMORR2HAGES）〉2分的冠心病合并房颤患者随机分为抗凝组与抗栓组,抗凝组使用华法林钠,抗栓组使用阿司匹林和氢氯吡格雷,随访观察4年,比较两组栓塞事件及出血事件的发生情况,并重新使用2010版血栓栓塞风险评估评分法（CHA2DS2-VASC）和出血风险评估法（HAS—BLED）进行回顾性评分。结果抗凝组栓塞事件发生较抗栓组明显减少,两组差异有统计学意义;而出血风险抗凝组较抗栓组有增高趋势．但差异无统计学意义。结论抗凝治疗可以减少高卒中高出血风险冠心病合并房颤患者栓塞风险。     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR?=?0.95; 95% CI, 0.89–1.02; P?=?.132) though significantly prolonged PFS (HR?=?0.82; 95% CI, 0.75–0.90; P?<?.001). Combination therapy significantly increased ORR (RR?=?1.32; 95% CI, 1.09–1.60; P?=?.005) and DCR (RR?=?1.26; 95% CI, 1.17–1.36, P?<?.001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR?=?1.54; 95% CI, 1.22–1.95; P?<?.001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR?=?1.49; 95% CI, 1.16–1.91; P?=?.002), but did not develop more diarrhea (RR?=?2.02; 95% CI, 0.86–4.77; P?=?.107) or rash (RR?=?1.29, 95% CI, 0.90–1.85; P?=?.172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.     

Population screening for atrial fibrillation by student pharmacists at health fairs

BackgroundIndividuals with unrecognized atrial fibrillation (AF) may be at an increased risk of stroke. There is a need to develop a sustainable and reproducible population-based screening model to identify unrecognized AF.ObjectiveThe objective of this study is to evaluate AF screening and education at student pharmacist–driven health fairs.MethodsScreening for AF was performed by student members of the American Pharmacist Association Academy of Student Pharmacists with preceptor oversight. Participants were screened using the KardiaMobile device (AliveCor, Mountain View, CA), a Food and Drug Administration–cleared device that interprets a medical-grade electrocardiogram in 30 seconds. Student pharmacists also calculated a CHA₂DS₂-VASc score. Participant education was provided using an American Heart Association AF patient information sheet. Learning assessment was evaluated with 3 multiple choice questions.ResultsStudents screened a total of 697 participants over a 6-month period at 13 health fairs. Overall, 71% of the participants were women aged 56 ± 15 years (mean ± SD). Sixteen of the participants (2.3%) who were screened received results indicating possible AF. None of the participants with a possible positive finding had symptoms suggestive of AF. Of these 16 participants, 11 (69%) had a CHA₂DS₂-VASc score greater than or equal to 2 (2.7 ± 0.7). Most participants answered each learning assessment question correctly. More than 95% of participants believed that screening for AF at health fairs was important or very important.ConclusionStudent pharmacist–driven health fairs were shown to be feasible models to screen for AF and were effective in providing AF education to the public. Student pharmacists also cultivated a clinical skill that is transferable to their future practice setting, including the community pharmacy setting. Additional studies are needed to assess whether population-based real-time assessment and detection of AF can reduce the risk of stroke in individuals with previously undetected AF.