Extended International Normalized Ratio testing intervals for warfarin-treated patients.

Essentials Warfarin typically requires International Normalized Ratio (INR) testing at least every 4 weeks. We implemented extended INR testing for stable warfarin patients in six anticoagulation clinics. Use of extended INR testing increased from 41.8% to 69.3% over the 3 year study. Use of extended INR testing appeared safe and effective. SUMMARY: Background A previous single-center randomized trial suggested that patients with stable International Normalized Ratio (INR) values could safely receive INR testing as infrequently as every 12 weeks. Objective To test the success of implementation of an extended INR testing interval for stable warfarin patients in a practice-based, multicenter collaborative of anticoagulation clinics. Methods At six anticoagulation clinics, patients were identified as being eligible for extended INR testing on the basis of prior INR value stability and minimal warfarin dose changes between 2014 and 2016. We assessed the frequency with which anticoagulation clinic providers recommended an extended INR testing interval (> 5 weeks) to eligible patients. We also explored safety outcomes for eligible patients, including next INR values, bleeding events, and emergency department visits. Results At least one eligible period for extended INR testing was identified in 890 of 3362 (26.5%) warfarin-treated patients. Overall, the use of extended INR testing in eligible patients increased from 41.8% in the first quarter of 2014 to 69.3% in the fourth quarter of 2016. The number of subsequent out-of-range next INR values were similar between eligible patients who did and did not have an extended INR testing interval (27.3% versus 28.4%, respectively). The numbers of major bleeding events were not different between the two groups, but rates of clinically relevant non-major bleeding (0.02 per 100 patient-years versus 0.09 per 100 patient-years) and emergency department visits (0.07 per 100 patient-years versus 0.19 per 100 patient-years) were lower for eligible patients with extended INR testing intervals than for those with non-extended INR testing intervals. Conclusions Extended INR testing for stable warfarin patients can be successfully and safely implemented in diverse, practice-based anticoagulation clinic settings.

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events.

OBJECTIVE: Treatment delays may result in different clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6-month mortality in reperfusion-treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE). DESIGN: Prospective, observational cohort study. SETTING: 106 hospitals in 14 countries. PATIENTS: 3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin-specific fibrinolytic drug or primary PCI. MAIN OUTCOME MEASURES: 6-month mortality. METHODS: Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score. RESULTS: A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6-month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6-month mortality increased by 0.30% per 10-min delay in door-to-needle time between 30 and 60 min compared with 0.18% per 10-min delay in door-to-balloon time between 90 and 150 min for patients undergoing primary PCI. CONCLUSIONS: Treatment delays in reperfusion therapy are associated with higher 6-month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.

Lack of clopidogrel-CYP3A4 statin interaction in patients with acute coronary syndrome.

OBJECTIVE: To assess a clinically significant interaction between cytochrome P450 3A4 (CYP3A4) metabolised statin and clopidogrel. DESIGN: Prospective single centre cohort study. SETTING: Academic teaching hospital in the USA. PATIENTS: 1651 patients presenting with acute coronary syndromes between January 1999 and February 2003 were studied. Data on baseline demographics, co-morbidities, and in-hospital management were collected. MAIN OUTCOME MEASURE: Association of CYP3A4 metabolised statin and clopidogrel use with in-hospital and six month mortality. The impact of the combined use of a CYP3A4 statin and clopidogrel on six month mortality and major adverse cardiac events was analysed by a risk adjusted logistic regression model. RESULTS: The odds ratios for six month mortality were: for CYP3A4 statin, 0.43 (95% confidence interval (CI) 0.27 to 0.71, p = 0.0009); for CYP3A4 statin plus clopidogrel, 0.36 (95% CI 0.23 to 0.60, p < 0.001); for non-CYP3A4 statin, 0.22 (95% CI 0.08 to 0.59, p = 0.002); and for non-CYP3A4 statin plus clopidogrel, 0.22 (95% CI 0.06 to 0.75, p = 0.016). CONCLUSIONS: Use of a combination of a CYP3A4 statin plus clopidogrel was associated with lower six month mortality and morbidity in patients with acute coronary syndromes. There was no significant difference in clinical benefit between a CYP3A4 statin and a non-CYP3A4 statin when used in conjunction with clopidogrel. This suggests that the proposed interaction is probably an ex vivo phenomenon and may not be clinically relevant.

Simple bedside additive tool for prediction of in-hospital mortality after percutaneous coronary interventions.

BACKGROUND: Risk-adjustment models for percutaneous coronary intervention (PCI) mortality have been recently reported, but application in bedside prediction of prognosis for individual patients remains untested. METHODS AND RESULTS: Between July 1, 1997 and September 30, 1999, 10 796 consecutive procedures were performed in a consortium of 8 hospitals. Predictors of in-hospital mortality were identified by use of multivariate logistic regression analysis. The final model was validated by use of the bootstrap technique. Additional validation was performed on an independent data set of 5863 consecutive procedures performed between October 1, 1999, and August 30, 2000. An additive risk-prediction score was developed by rounding coefficients of the logistic regression model to the closest half-integer, and a visual bedside tool for the prediction of individual patient prognosis was developed. In this patient population, the in-hospital mortality rate was 1.6%. Multivariate regression analysis identified acute myocardial infarction, cardiogenic shock, history of cardiac arrest, renal insufficiency, low ejection fraction, peripheral vascular disease, lesion characteristics, female sex, and advanced age as independent predictors of death. The model had excellent discrimination (area under the receiver operating characteristic curve, 0.90) and was accurate for prediction of mortality among different subgroups. Near-perfect correlation existed between calculated scores and observed mortality, with higher scores associated with higher mortality. CONCLUSIONS: Accurate predictions of individual patient risk of mortality associated with PCI can be achieved with a simple bedside tool. These predictions could be used during discussions of prognosis before and after PCI.

Comparison of artificial neural networks with logistic regression in prediction of in-hospital death after percutaneous transluminal coronary angioplasty.

OBJECTIVES: Our objective was to compare artificial neural networks (ANNs) with logistic regression for prediction of in-hospital death after percutaneous transluminal coronary angioplasty and to assess the impact of guiding initial ANN variable selection with univariate analysis. BACKGROUND: ANNs can detect complex patterns within data. Criticisms include the unpredictability of variable selection. They have not previously been applied to outcomes modeling for percutaneous coronary interventions. METHODS: A database of consecutive (n = 3019) percutaneous transluminal coronary angioplasty procedures from an academic tertiary referral center between July 1994 and July 1997 was used. An ANN was developed for 38 variables (unguided model) (n = 1554). A second model was developed with predictors from an univariate analysis (guided model). Both were compared with a logistic regression model developed from the same database. Model validation was performed on independent data (n = 1465). Model predictive accuracy was assessed by the area under receiver operating characteristic curves. Goodness of fit was assessed with the Hosmer-Lemeshow statistic. RESULTS: Sixty unguided and guided ANNs were developed. Predictive accuracy and model calibration for all models were similar for training data but were significantly better for logistic regression for independent validation data. Overestimation of event rate in higher risk patients accounted for the majority of discrepancy in model calibration for the ANNs. This difference was partially amended by guiding variable selection. CONCLUSION: ANNs were able to model in-hospital death after percutaneous transluminal coronary angioplasty when guiding variable selection. However, performance was not better than traditional modeling techniques. Further investigations are needed to understand the impact of this methodology on outcomes analysis.

Evaluating and improving the delivery of heart care: the University of Michigan experience.

With increasing pressure to curb escalating costs in medical care, there is particular emphasis on the delivery of cardiovascular services, which account for a substantial portion of the current healthcare dollar spent in the United States. A variety of tools were used to improve performance at the University of Michigan Health System, one of the oldest university-affiliated hospitals in the United States. The tools included initiatives to understand outcomes after coronary bypass operations and coronary angioplasty through use of proper risk-adjusted models. Critical pathways and guidelines were implemented to streamline care and improve quality in interventional cardiology, management of myocardial infarction, and preoperative assessment of patients undergoing vascular operations. Strategies to curb unnecessary costs included competitive bidding of vendors for expensive cardiac commodities, pharmacy cost reductions, and changes in nursing staff. Methods were instituted to improve guest services and partnerships with the community in disease prevention and health promotion.

The physician's role in minimizing prehospital delay in patients at high risk for acute myocardial infarction: recommendations from the National Heart Attack Alert Program. Working Group on Educational Strategies To Prevent Prehospital Delay in Patients at High Risk for Acute Myocardial Infarction.

Physicians and other health care professionals play an important role in reducing the delay to treatment in patients who have an evolving acute myocardial infarction. A multidisciplinary working group has been convened by the National Heart Attack Alert Program (which is coordinated by the National Heart, Lung, and Blood Institute of the National Institutes of Health) to address this concern. The working group's recommendations target specific groups of patients: those who are known to have coronary heart disease, atherosclerotic disease of the aorta or peripheral arteries, or cerebrovascular disease. The risk for acute myocardial infarction or death in such patients is five to seven times greater than that in the general population. The working group recommends that these high-risk patients be clearly informed about symptoms that they might have during a coronary occlusion, steps that they should take, the importance of contacting emergency medical services, the need to report to an appropriate facility quickly, treatment options that are available if they present early, and rewards of early treatment in terms of improved quality of life. These instructions should be reviewed frequently and reinforced with appropriate written material, and patients should be encouraged to have a plan and to rehearse it periodically. Because of the important role of the bystander in increasing or decreasing delay to treatment, family members and significant others should be included in all instruction. Finally, physicians' offices and clinics should devise systems to quickly assess patients who telephone or present with symptoms of a possible acute myocardial infarction.