Is quality of anticoagulation a 'wild card' in the treatment of patients with atrial fibrillation?
Explore the source record for details and available documents.
Comment↗
Biomedical subjects
Greg C Flaker
Publications and source records attributed to Greg C Flaker.
Comparing classifications of death in the Mode Selection Trial: agreement and disagreement among site investigators and a clinical events committee.
Clinical events committees (CECs) are the current standard for endpoint adjudication in clinical trials. However, little data exist with which to compare CEC and site investigator determinations or to evaluate internal agreement among CEC members. Using data from the Mode Selection Trial in Sinus Node Dysfunction (MOST), we analyzed classifications of death in order to compare internal agreement among CEC physician reviewers and agreement between the CEC and site investigators. Death was classified at 2 levels: by major cause (cardiac, noncardiac, or unknown) and by minor subclassification of the major classifications. Reviewer agreement was tabulated at the major and minor levels, and standard and weighted kappa statistics were calculated. Disagreement at both levels was also determined. Individual decision-making was tabulated in terms of frequency in classifying death as unknown. All 404 deaths were classified by the CEC. Site investigators determined major classifications in 382 cases and minor classification in 379 cases. The CEC and the site investigators disagreed in classifying 41 cases (10.7%) at the major level and 117 (30.9%) at the minor level. CEC reviewers disagreed internally at the major level in 64 cases (15.8%), at the minor level in 63 cases (15.6%), and at any level in 127 cases (31.4%) (kappa = 0.60, 95% confidence interval (CI) [0.55, 0.66]; weighted kappa = 0.66, 95% CI [0.62, 0.75]). In resolving internal disagreements, the full CEC agreed with 1 of 2 CEC reviewers in 85.9% of cases. Disagreements occurred between site investigators and CEC reviewers in classifying deaths. Endpoint determination and decision-making varied among individual CEC reviewers, but second-tier reviews by the full CEC resolved all disagreements. These findings support continued use of CECs for endpoint adjudication in clinical trials.
Cause of Death↗
Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.
BACKGROUND: Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. METHODS: We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. RESULTS: The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). CONCLUSIONS: Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.
Aged↗
Asymptomatic atrial fibrillation: demographic features and prognostic information from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.
BACKGROUND: Atrial fibrillation (AF) may occur without symptoms. Little is known about demographic features and prognostic information in patients with asymptomatic AF. METHODS: In the AFFIRM study, 4060 patients were randomized to either rhythm or rate control. At baseline, patients were identified as asymptomatic if they answered "no" to a 15-item questionnaire related to cardiac symptoms during AF in the 6 months before study entry. RESULTS: There were 481 (12%) asymptomatic patients at baseline. Compared with symptomatic patients, asymptomatic patients were more often men and had a lower incidence of coronary artery disease and congestive heart failure, but had more cerebrovascular events. Asymptomatic patients had a longer duration of AF, a lower maximum heart rate, and better left ventricular function. They received fewer cardiac medications and fewer therapies to maintain sinus rhythm. At 5 years, there was a trend for better survival in asymptomatic patients (81% vs 77%, P = .058), and they were more likely to be free from disabling stroke or anoxic encephalopathy, major bleeding, and cardiac arrest (79% vs 67%, P = .024). However, mortality and major events were similar after correction for baseline differences. CONCLUSIONS: Patients with asymptomatic AF have less serious heart disease but more cerebrovascular disease. Asymptomatic patients receive different therapies than symptomatic patients. However, the absence of symptoms and the differences in treatment does not confer a more favorable prognosis when differences in baseline clinical parameters are considered. Anticoagulation should be considered in these patients.
Aged↗
Heart failure hospitalization is more common in pacemaker patients with sinus node dysfunction and a prolonged paced QRS duration.
OBJECTIVES: The purpose of this study was to determine whether a prolonged paced QRS duration increases the risk of cardiac dysfunction. BACKGROUND: Right ventricular apical pacing mimics left bundle branch block, results in a prolonged QRS duration of variable duration, and causes ventricular desynchronization. METHODS: In the Mode Selection Trial (MOST), QRS duration was measured in patients who had at least one paced ventricular complex recorded on 12-lead ECG within 3 months of enrollment (early) and after 9 months (late). Clinical endpoints including heart failure hospitalization, mortality, and atrial fibrillation were analyzed. A total of 1,026 patients were included in the analysis. Median age was 75 years (25th, 75th percentiles = 69, 80) and median ejection fraction prior to implant was 55% (45, 60). The cumulative percent ventricular pacing (DDDR and VVIR) was 81% over a median follow-up of 33 months. During period, 123 patients had heart failure hospitalization, 197 died, and 261 patients had atrial fibrillation. RESULTS: Cox proportional hazards models demonstrated that paced QRS duration was a strong predictor of heart failure hospitalization (hazard ratio 1.15; 95% confidence interval 1.07,1.23) for each 10-ms increase in paced QRS duration (P = .001). The increased risk was unaffected by adjustment for other known predictors of heart failure hospitalization in the study. Paced QRS duration was not significant for mortality (P = .41) or atrial fibrillation (P = .20) when baseline QRS duration and other predictors were included. CONCLUSIONS: Paced QRS duration is a significant, independent predictor of heart failure hospitalization in patients with sinus node dysfunction. A very long paced QRS duration is associated with increased heart failure hospitalization.
Aged↗
"Show-me" the money.
Explore the source record for details and available documents.
Defibrillators, Implantable↗
Clinical and quality of life comparison of accelerometer, piezoelectric crystal, and blended sensors in DDDR-paced patients with sinus node dysfunction in the mode selection trial (MOST).
INTRODUCTION: Permanent pacemakers are capable of increasing heart rate in response to physical activity by a variety of sensors including accelerometers, piezoelectric crystals, or blended sensors. The impact of these different physiologic sensors on cardiovascular events and quality of life is not known. METHODS: Of 2,010 patients randomized in the Mode Selection Trial, 1,245 patients were selected with the most commonly used pacemakers with these three sensors. Clinical characteristics and quality of life were compared between groups at baseline, 3 months, and then yearly. RESULTS: There were 449 patients with an accelerometer sensor device, 682 with a piezoelectric sensor, and 114 with a blended sensor. The groups were similar in terms of age (mean 74 years), gender, and cardiac risk factors but differences existed in weight, heart rate, mitral regurgitation, revascularization history, and drug therapy. The median ventricular pacing frequency was 80% (25th, 75th percentiles 42, 97). After a median follow-up of 33.1 months, the risk of death, heart failure hospitalization, atrial fibrillation, and the combined endpoint of mortality and stroke was not significantly different between the sensor types, after adjustment for baseline differences. Quality of life analyses demonstrated that patients with blended sensors had significantly worse (P < 0.01) physical function than did patients with the other two sensor systems. Moreover, patients receiving blended sensors had the poorest absolute scores, without reaching statistical significance, on 9 of 13 quality of life measures after adjusting for differences in the groups. CONCLUSION: We found no significant differences among the three most utilized sensors in clinical endpoints. Those patients who received blended sensors had worse physical function quality of life scores. However, clinical selection of the most sophisticated sensor for the most ill patients cannot be excluded as an explanation of these results.
Aged↗
Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction.
BACKGROUND: Diabetes is a major risk factor for developing coronary heart disease. In patients with diabetes who survived myocardial infarction (MI), less is known about subsequent morbidity and mortality. We evaluated the effects of diabetes in post-MI patients with left ventricular dysfunction on cardiovascular events and death. METHODS: The Survival and Ventricular Enlargement, a randomized, double-blind, placebo-controlled multicenter trial, evaluated the efficacy of captopril vs placebo in 2231 patients following acute MI with left ventricular dysfunction defined as an ejection fraction less than or equal to 40%. Patients were randomly assigned to captopril or placebo 3 to 16 days following MI and were followed up for 2 to 5 years (mean, 3.5 years). RESULTS: Among the 2231, 496 (22.2%) were patients with a history of diabetes, of which 168 (33.9%) were treated with insulin. Patients with diabetes were significantly older; more likely to be women; have a history of prior MI or hypertension; be obese or manifest Killip class II or greater; and have higher systolic blood pressure, pulse pressure, and heart rate, as well as lower ejection fraction. During follow-up, 31.3% of patients with diabetes and 20.1% of nondiabetic patients died (P<.001). Furthermore, 50% of the patients with diabetes had at least 1 major cardiovascular event compared with 32.3% among the nondiabetic patients (P<.001). In multivariate analysis that adjusted for all significant differences in baseline characteristics, patients with diabetes had a 39% higher total mortality (P = .001) and 49% more cardiovascular events (P = .001). Among the patients with diabetes, baseline insulin treatment was associated with a greater risk of death (41.1% vs 26.2%; P = .001) and cardiovascular events (58.3% vs 45.7%; P = .008). CONCLUSIONS: In patients who survived MI with left ventricular dysfunction, diabetes increased risk of death from all causes even after controlling for differences in other risk factors. Patients with diabetes treated with insulin have a particularly higher mortality risk. Patients with diabetes who survived MI with left ventricular dysfunction, in particular those receiving insulin, are at high risk of subsequent mortality and cardiovascular events and thus require intensive risk factor modification, as well as evaluation for novel therapies.
Aged↗
Predictors of stroke in patients paced for sick sinus syndrome.
OBJECTIVES: This study was an analysis of factors associated with stroke in a population of patients paced for sinus node dysfunction in a large prospective clinical trial (Mode Selection Trial [MOST]). BACKGROUND: The effects of dual-chamber versus single-chamber ventricular pacing on subsequent stroke in patients with sinus node dysfunction are not known. METHODS: A total of 2,010 patients with sinus node dysfunction were randomized to ventricular or dual-chamber pacing and followed for a median of 33.1 months. RESULTS: The median participant age was 74 years. During 5,664 patient-years of follow-up, 90 strokes (11 hemorrhagic) occurred. By life-table analysis, the rate of stroke was 2.2% (95% confidence interval [CI] 1.6 to 2.9) at one year and 5.8% (95% CI 4.5 to 7.1) at four years. The incidence of stroke was not significantly different in dual-chamber (4%) as compared with ventricular-paced patients (4.9%) (hazard ratio [HR] 0.82, 95% CI 0.54 to 1.25, p = 0.36). Multivariable analysis demonstrated that significant predictors of stroke included prior stroke or transient ischemic attack, Caucasian race, hypertension, prior systemic embolism, and New York Heart Association functional class III or IV (p < 0.05); pacing mode remained non-significant after adjustment for these factors (p = 0.37). Clinically reported atrial fibrillation after implantation was a risk factor for stroke in this cohort after adjustment for other predictors of stroke (p = 0.042, HR 1.68 [95% CI 1.02 to 2.76]). CONCLUSIONS: Clinical characteristics, but not mode of pacing, were associated with subsequent stroke in patients paced for sinus node dysfunction.
Age Factors↗
Why is warfarin underutilized in patients with atrial fibrillation?
Explore the source record for details and available documents.
Anticoagulants↗
Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study.
OBJECTIVES: We sought to determine the predictors of heart failure (HF) development in long-term survivors of myocardial infarction (MI). BACKGROUND: Modern strategies of acute MI care have resulted in an increasing proportion of survivors at heightened risk of future non-fatal events, including HF. METHODS: We assessed the risk of developing HF in 3860 stable MI patients without a previous history of HF, who were enrolled in the Cholesterol And Recurrent Events (CARE) trial a median of 10 months post MI. Baseline characteristics of patients who did or did not develop HF during the five years of observation were assessed. RESULTS: A total of 243 patients (6.3%) developed HF in a linear pattern at a rate of 1.3%/year. Heart failure development markedly increased the risk of death (hazard ratio 10.2, 95% confidence interval 7.7 to 13.5). Fifty-seven patients (23.5%) who developed HF had a recurrent MI between enrollment and the onset of HF, increasing the risk fivefold. The most important predictors of HF were age and left ventricular ejection fraction. Other predictors included diabetes, history of hypertension, previous MI, and baseline heart rate. Moderate exercise three or more times per week was independently associated with a 30% lower risk of HF. CONCLUSIONS: Heart failure post MI occurs in a time-dependent fashion, which is usually not a direct consequence of a detectable interim MI. Patients who experience late-onset HF have a 10-fold increased risk of death compared with other MI survivors. Baseline characteristics can risk stratify patients at high risk of subsequent HF.
Age Factors↗
Window to the heart: the value of a native and paced QRS duration. Current perspective and review.
Given the technological advances and reliance upon expensive testing for guiding therapy, it is surprising how an inexpensive, low tech electrocardiogram can provide a wealth of information pertaining to the underlying cardiovascular status of a patient. In this article we review the changes in hemodynamics, prognosis and guidance of therapeutic options associated with a prolonged QRS duration.
Bundle-Branch Block↗
High defibrillation thresholds in transvenous biphasic implantable defibrillators: clinical predictors and prognostic implications.
The aim of this study was to identify clinical characteristics that distinguish patients with high DFTs and assess the prognostic implication. DFTs testing is a lengthy, potentially painful, and a hazardous process. Little information is available concerning the identification of patients with high DFT who undergo ICD surgery with transvenous leads and biphasic energy. This study analyzed 968 patients from two separate clinical studies who received a Medtronic cardioverter defibrillator from January 1995 through November 1999 and who had DFT testing measured by a binary search protocol. Compared to 865 patients with low defibrillation thresholds (< 18 J), the 103 patients with high thresholds (> or = 18 J) had a lower LVEF (34 +/- 16.7 vs 38.3 +/- 16.2%, P = 0.01), a worse NYHA functional class (23% Class I, 43% Class II, 29% Class III, 5% Class IV vs. 27% Class I, 55% Class II, 17% Class III, 1% Class IV, P < 0.0001), had bypass surgery less often (10.7 vs 27.5%, P < 0.0001), used amiodarone within the past 6 weeks (42.7 vs 27.2%, P = 0.002), and had a history of ventricular fibrillation more often (44.7 vs 33.1%, P = 0.02). Information concerning the number of shocks delivered was available in 345 (35%) patients; 23 were in the high DFT group and 322 were in the low DFT group. Twelve (52%) of the 23 patients in the high DFT arm received 3.6 +/- 2.7 shocks (median 2.5) and 106 (33%) of the 322 patients with low DFT received 4.9 +/- 9.5 shocks (median 2). After 6 months the mortality rate of patients with high thresholds was 11.7 vs 7.8% in patients with low thresholds (P = 0.118). Using a multivariate logistic regression model the significant predictors of death were older age, higher NYHA class, lower LVEF, amiodarone use, had a presenting arrhythmia of ventricular fibrillation and CHF but not initial high defibrillation thresholds. The study found that (1) 11% of patients have high DFTs, (2) clinical characteristics that identify high defibrillation thresholds are NYHA Class III, IV, low ejection fraction, no previous history of bypass surgery, prior amiodarone use preoperatively, and presenting with ventricular fibrillation, and (3) while high DFTs were associated with a more ill patient population, there was no difference in survival in a 6-month follow-up. Patients with a predicted low DFTs may be eligible for abbreviated ICD testing while high risk patients require formal testing.
Case-Control Studies↗