Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Transesophageal echocardiographic diagnosis of a WATCHMAN left atrial appendage closure device thrombus 10 years following implantation.

Left atrial appendage closure with the WATCHMAN device is an alternative to chronic oral anticoagulation for thromboembolic prophylaxis in atrial fibrillation patients. Left atrial device-related thrombus (DRT) has been described in the first year after implant with an incidence of ~6%. A 79-year-old man underwent WATCHMAN device placement in 2006. Routine protocol specified follow-up transesophageal echocardiograms (TEE) at 6 weeks, 6 months, and 1 year following implant showed no evidence for DRT or peri-device flow. A decade after device implant, the patient presented with severe symptomatic aortic stenosis and underwent repeat TEE, which revealed a 21 mm × 18 mm DRT on the LA aspect of the WATCHMAN device. He was prescribed apixaban 5 mg po BID. A TEE performed 111 days later demonstrated marked diminution in the DRT (9 mm in diameter). This case demonstrates that WATCHMAN DRT may occur late following implantation.

Resolution (and Late Recurrence) of WATCHMAN Device-Related Thrombus Following Treatment with Dabigatran.

The WATCHMAN left atrial (LA) appendage closure system is an alternative therapy for stroke prevention in patients with atrial fibrillation who are intolerant to chronic oral anticoagulation with warfarin. Infrequently, LA device-related thrombus (DRT) has been suspected. Optimal treatment of DRT is not known, and the efficacy of novel oral anticoagulants (NOAC) in this setting has not been previously described. A 69-year-old woman with permanent atrial fibrillation underwent WATCHMAN device placement. A transesophageal echocardiogram (TEE) performed 45 days following implant revealed a well-seated device. A 1-year follow-up TEE revealed a 1.2 × 0.8 cm sized DRT on the LA aspect of the WATCHMAN device. She was prescribed dabigatran 150 mg po BID for 3 months and she remained on aspirin 325 mg per day. She returned approximately 4 months later (and several weeks after completing her 3-month course of dabigatran) for a repeat TEE, which revealed complete resolution of the DRT. A TEE was performed approximately 8 months later and revealed a new DRT measuring 1 cm in diameter on the LA aspect of the device. This is the first report of successful WATCHMAN DRT treatment with a NOAC, and the first report of late DRT recurrence following treatment to resolution with an anticoagulant. This case report demonstrates that (1) WATCHMAN DRT may form late following implantation, (2) DRT resolution is possible with NOACs, specifically dabigatran, and (3) late recurrence of DRT is possible, even after treatment to initial resolution with systemic anticoagulation.

Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-Year Follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) Trial.

BACKGROUND: The multicenter PROTECT AF study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) was conducted to determine whether percutaneous left atrial appendage closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation. METHODS AND RESULTS: Patients (n=707) with nonvalvular atrial fibrillation and at least 1 risk factor (age >75 years, hypertension, heart failure, diabetes, or prior stroke/transient ischemic attack) were randomized to either the Watchman device (n=463) or continued warfarin (n=244) in a 2:1 ratio. After device implantation, warfarin was continued for ≈45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups, respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy end point included stroke, systemic embolism, and cardiovascular death, and the primary analysis was by intention to treat. After 1588 patient-years of follow-up (mean 2.3±1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100 patient-years) in the Watchman and warfarin groups, respectively (relative risk, 0.71; 95% confidence interval, 0.44%-1.30% per year), which met the criteria for noninferiority (probability of noninferiority >0.999). There were more primary safety events in the Watchman group (5.5% per year; 95% confidence interval, 4.2%-7.1% per year) than in the control group (3.6% per year; 95% confidence interval, 2.2%-5.3% per year; relative risk, 1.53; 95% confidence interval, 0.95-2.70). CONCLUSIONS: The "local" strategy of left atrial appendage closure is noninferior to "systemic" anticoagulation with warfarin. PROTECT AF has, for the first time, implicated the left atrial appendage in the pathogenesis of stroke in atrial fibrillation. CLINICAL TRIAL REGISTRATION: : URL: http://www.clinicaltrials.gov. Unique identifier: NCT00129545.

Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial.

IMPORTANCE: While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions. OBJECTIVE: To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin. DESIGN, SETTING, AND PARTICIPANTS: PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2 score ≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5% and superiority a probability of 95% or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups. INTERVENTIONS: Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3). MAIN OUTCOMES AND MEASURES: A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat. RESULTS: At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95% credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, >99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95% CI, 0.21-0.75; P = .005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95% CI, 0.45-0.98; P = .04). CONCLUSIONS AND RELEVANCE: After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00129545.

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.

BACKGROUND: The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. OBJECTIVES: The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. METHODS: PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. RESULTS: For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively). CONCLUSIONS: These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441).

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.

Attainment of goals from national guidelines among persons with type 2 diabetes: a cohort study in an academic family medicine setting.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with diabetes, but goals for reduction of modifable cardiovascular risk factors are difficult to achieve in primary care. We evaluated the change in risk factor control for a cohort of patients with diabetes and hyperlipidemia over a four-year period, as well as the change in proportion of patients meeting clinical practice guideline goals. METHODS: Medical records were reviewed from a cohort of 86 randomly selected persons with type 2 diabetes in an academic family medicine setting. Data were abstracted to assess the attainment of and change in five treatment goals related to glycemic, blood pressure, and lipid control from 1999-2003. Descriptive statistics were applied to demographic variables. Mean differences in outcomes were assessed with the paired t-test. The McNemar test was used to assess non-parametric variables, and the Wilcoxon signed ranks test was applied to differences achieved in mean goal scores for outcome variables. RESULT: The mean numbers of treatment goals attained were 2.76 (SD = 0.92) in 1999 and 2.48 (SD = 1.1) in 2003. Significant improvements were noted in the mean values of HbA1c (0.4% decrease, p = 0.03), diastolic blood pressure (4.3mmHg decrease, p < 0.001), low-density lipoprotein cholesterol (LDL-C; 10.6 mg/dL decrease, p < 0.01), and high-density lipoprotein cholesterol (HDL-C; 8.3 mg/dL increase, p < 0.001) over the four-year study interval. No significant differences were noted in the percent at goal during the study for HDL-C or for HbA1c. A significant decrease was found in the percent at goal from 1999-2003 for LDL-C from 79% to 40%, respectively). The decrease in the percent LDL-C at goal was explained by the more stringent practice guideline goals introduced in 2001 for diabetes (i.e., LDL-C < 100 mg/dL). CONCLUSION: Despite significant improvement in mean values of modifiable risk factors, the percent of patients meeting 2003 guideline goals for HbA1c, systolic blood pressure, and LDL cholesterol did not improve. These findings suggest that patient-level improvements may not be adequate indicators of a practices achievement of guideline recommendations. Percent attainment of guideline goals may be a useful peformance measure of practice-level quality improvement initiatives.

Bleeding Outcomes After Left Atrial Appendage Closure Compared With Long-Term Warfarin: A Pooled, Patient-Level Analysis of the WATCHMAN Randomized Trial Experience.

OBJECTIVES: The purpose of this study was to compare the relative risk of major bleeding with left atrial appendage (LAA) closure compared with long-term warfarin therapy. BACKGROUND: LAA closure is an alternative approach to chronic oral anticoagulation for the prevention of thromboembolism in patients with atrial fibrillation (AF). METHODS: We conducted a pooled, patient-level analysis of the 2 randomized clinical trials that compared WATCHMAN (Boston Scientific, Natick, Massachusetts) LAA closure with long-term warfarin therapy in AF. RESULTS: A total of 1,114 patients were included, with a median follow-up of 3.1 years. The overall rate of major bleeding from randomization to the end of follow-up was similar between treatment groups (3.5 events vs. 3.6 events per 100 patient-years; rate ratio [RR]: 0.96; 95% confidence interval [CI]: 0.66 to 1.40; p = 0.84). LAA closure significantly reduced bleeding >7 days post-randomization (1.8 events vs. 3.6 events per 100 patient-years; RR: 0.49; 95% CI: 0.32 to 0.75; p = 0.001), with the difference emerging 6 months after randomization (1.0 events vs. 3.5 events per 100 patient-years; RR: 0.28; 95% CI: 0.16 to 0.49; p < 0.001), when patients assigned to LAA closure were able to discontinue adjunctive oral anticoagulation and antiplatelet therapy. The reduction in bleeding with LAA closure was directionally consistent across all patient subgroups. CONCLUSIONS: There was no difference in the overall rate of major bleeding in patients assigned to LAA closure compared with extended warfarin therapy over 3 years of follow-up. However, LAA closure significantly reduced bleeding beyond the procedural period, particularly once adjunctive pharmacotherapy was discontinued. The favorable effect of LAA closure on long-term bleeding should be considered when selecting a stroke prevention strategy for patients with nonvalvular AF. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy [PREVAIL]; NCT01182441).

Diabetes mellitus is associated with a shift in the temporal risk profile of inhospital death after percutaneous coronary intervention: an analysis of 25,223 patients over 20 years.

BACKGROUND: Numerous studies have demonstrated that patients with diabetes have higher rates of restenosis, late myocardial infarction, and late death after percutaneous coronary interventions (PCI). However, it remains unclear whether patients with diabetes mellitus also have an increased hazard for early death after either elective or urgent PCI. METHODS: Patients undergoing PCI at the Mid American Heart Institute between 1980 and 1999 were identified. The main end point was inhospital death. Patients were stratified both by diabetes status and whether they underwent elective or urgent PCI. RESULTS: There were 17,341 nondiabetic patients and 4308 patients with diabetes who underwent elective PCI. There were 2946 nondiabetic patients and 628 patients with diabetes who underwent urgent PCI. Multivariate analysis demonstrated that diabetes was associated with increased inhospital mortality rate after any PCI (odds ratio 1.4, 95% CI 1.1-1.8, P =.003). The unadjusted inhospital mortality rates for the nondiabetic patients and patients with diabetes were 0.8% and 1.4%, respectively (P <.001), after elective PCI. The mortality rate was 6.9% for the nondiabetic patients and 12.7% for the patients with diabetes (P <.001) after urgent PCI. The inhospital mortality rates among diabetic patients appear to be decreasing over time among the elective cohort (elective PCI diabetes-time interaction, P =.007) but not in the urgent cohort (urgent PCI-diabetes-time interaction, P =.68). CONCLUSIONS: There has been an improvement in the inhospital survival rate among patients with diabetes in the elective PCI cohort. This improved hospital survival has yet to be realized among patients with diabetes undergoing urgent PCI.

Multivessel percutaneous coronary intervention in patients with multivessel disease and acute myocardial infarction.

BACKGROUND: The optimal percutaneous interventional strategy for dealing with significant non-culprit lesions in patients with multivessel disease (MVD) with acute myocardial infarction (AMI) at presentation remains controversial. METHODS: A total of 820 patients treated with primary angioplasty for AMI between 1998 and 2002 were classified in groups of patients with single vessel disease (SVD) or MVD (> or =70% stenosis of > or =2 coronary arteries). Patients with MVD were subdivided in 3 groups on the basis of the revascularization strategy: 1) patients undergoing percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) only; 2) patients undergoing PCI of both the IRA and non-IRA(s) during the initial procedure; and 3) patients undergoing PCI of the IRA followed by staged, in-hospital PCI of the non-IRA(s). Procedural, 30-day, and 1-year outcomes are reported. RESULTS: At 1 year, compared with patients with SVD, patients with MVD had a higher incidence of re-infarction (5.9% vs 1.6%, P =.003), revascularization (18% vs 9.6%, P <.001), mortality (12% vs 3.2%, P <.001), and major adverse cardiac events (MACEs; 31% vs 13%, P <.001). In patients with MVD, compared with PCI restricted to the IRA only, multivessel PCI was associated with higher rates of re-infarction (13.0% vs 2.8%, P <.001), revascularization (25% vs 15%, P =.007), and MACEs (40% vs 28%, P =.006). Multivessel PCI was an independent predictor of MACEs at 1 year (odds ratio = 1.67, P =.01). CONCLUSIONS: These data suggest that in patients with MVD, PCI should be directed at the IRA only, with decisions about PCI of non-culprit lesions guided by objective evidence of residual ischemia at late follow-up. Further studies are needed to confirm these findings.

Improving in-hospital mortality in the setting of an increasing risk profile among patients undergoing catheter-based reperfusion for an acute myocardial infarction without cardiogenic shock.

UNLABELLED: Prompt myocardial reperfusion is the therapeutic goal for patients presenting with acute myocardial infarction (AMI). However, there remains a paucity of clinical data from single centers solely dedicated to a catheter-based reperfusion strategy. Therefore, we sought to identify significant predictors of in-hospital mortality, to determine the changing profile of patient demographics and to identify the mortality trend over time. METHODS: Consecutive patients who underwent percutaneous coronary intervention (PCI) for an AMI between January of 1982 and December of 1999 were included in this multivariable analysis (excluding cardiogenic shock). AMI was defined as an evolving myocardial infarction within the preceding 24 hours. The primary endpoint for this analysis was in-hospital mortality. RESULTS: There were 2,745 patients identified in this study, of which 8.3% (n = 228) were non-survivors. The significant multivariable predictors of in-hospital mortality included creatinine > 1.5 mg/dl [relative risk (RR), 5.7; 95% confidence interval (CI) 4.0 8.1], ejection fraction < 40% (RR, 6.6; 95% CI, 4.3 10.0), multivessel disease (RR, 2.8; 95% CI, 1.9 4.2), female (RR, 2.3; 95% CI, 1.6 3.1) and age > 70 years (RR, 1.6; 95% CI, 1.1 2.2). The incidence of patients with these high-risk characteristics increased in recent years; thus, the unadjusted slope of the mortality trend over 20 years was not significant. However, following adjustment for the temporal shift in high-risk variables, there was a significant reduction in the adjusted in-hospital mortality rate (RR, 0.89; 95% CI 0.8 0.98; p = 0.017). Despite the changing risk profile, the short-term mortality continues to improve for patients undergoing AMI PCI.

Regular use of aspirin and pancreatic cancer risk.

BACKGROUND: Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. METHODS: In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72-1.39). No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. CONCLUSIONS: These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.

BACKGROUND: In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified. OBJECTIVES: The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy. METHODS: This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed. RESULTS: At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days' postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: -0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small. CONCLUSIONS: In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days' post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy.

Contrast enhanced transesophageal echocardiographic guidance of left atrial appendage closure device implantation.

The percutaneous implantation of a left atrial appendage closure device offers an alternative to chronic oral anticoagulation in patients with nonvalvular atrial fibrillation and concomitant risk factors for stroke. Transesophageal echocardiography plays a key role in defining left atrial appendage anatomy and in guiding device implantation. The authors describe a case in which contrast-enhanced transesophageal echocardiography was critically important in spatially resolving the borders of the left atrial appendage, which ultimately led to successful device implantation with cessation of warfarin therapy.

Contraceptive choices of women 35-44 years of age: findings from the behavioral risk factor surveillance system.

PURPOSE: With an estimated 3.1 million unintended pregnancies in the United States each year, patterns of contraceptive use have significant public health importance. Little literature has focused on these patterns in women over age 35. METHODS: Using data from the 2004 Behavioral Risk Factor Surveillance System, we conducted a population-based analysis of 22,890 women between the ages of 35-44 years who completed information on family planning. Lifestyle, demographic, and medical history covariates were assessed and multinomial logistic regression was used to obtain odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Female sterilization was the most popular contraceptive method among women aged 35-44 years (28.5%). Relative to non-Hispanic white women, Hispanic and non-Hispanic black women were less likely to use effective methods of contraception such as male sterilization (OR = 0.33, 95% CI: 0.23, 0.46; and OR = 0.10, 95% CI: 0.06, 0.16, respectively) and oral contraceptives (OR = 0.55, 95% CI: 0.41, 0.73; and OR = 0.42, 95% CI: 0.31, 0.57, respectively) after adjustment for demographic, lifestyle, and medical factors. CONCLUSIONS: Although fecundity is reduced in women of this age group, increased rates of maternal and fetal complications make unintended pregnancies riskier. This study demonstrates opportunities for targeted counseling and increased awareness of the diversity of contraceptive choices for older women.