Controversies in Hypertension I: The Optimal Assessment of Blood Pressure Load and Implications for Treatment.

The most important factor in treating hypertension is assessing an individual patient's true blood pressure load, the cornerstone being research-grade office determination. Office blood pressure should be supplemented with out-of-office measurement, including home and ambulatory monitoring (if available), which we consider complementary and not interchangeable. Controversy remains for initiation of treatment of white coat hypertension, where cardiovascular risk lies between normotension and sustained hypertension; antihypertensive therapy should be considered unless low cardiovascular risk, wherein pressures should be followed for progression to sustained hypertension. Available data do not support intensification of therapy for the white coat effect due to the similar cardiovascular risk to controlled hypertension. Given the higher cardiovascular risk of the masked effect, initiation of therapy for masked hypertension and intensification for masked uncontrolled hypertension are indicated, acknowledging the dearth of supporting data. Optimally, randomized controlled trials are needed to determine the benefit of treating the 4 incongruous phenotypes between office and out-of-office measurements, that is, those with white coat or masked effects. We make no recommendations regarding chronotherapy pending results of ongoing trials.

Assessment of Comorbidity Burden and Treatment Response: Reanalysis of the SCD-HEFT Trial.

INTRODUCTION: Comorbidity burden may be associated with treatment-effect heterogeneity (HTE) in clinical trials, which could alter the interpretation or clinical translation of results for many patients in the real world. OBJECTIVE: In this analysis, we sought to determine the distribution of multimorbidity scores in patients enrolled in SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) and tested the association between comorbidity burden and treatment efficacy for the outcome of all-cause death. METHODS: Each patient was assigned a modified Charlson Comorbidity Index (mCCI) score from 1 to 14 based on available enrollment data. We investigated the relationship between mCCI score and time to all-cause death using Cox proportional hazards models. Models were fit for quartiles of the comorbidity index, reference coding was used, with quartile 1 (Q1; mCCI score of 1-2) selected as the reference. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were reported from these models. Following the same analysis framework as the original manuscript, patients assigned to amiodarone or implantable cardioverter-defibrillator (ICD) were compared with those assigned to placebo in separate Cox models. Each model included the mCCI score in quartiles, group assignment, and an interaction term for the quartile and group assignment. HRs and corresponding 97.5% CIs were reported from these models. RESULTS: The majority of patients had an mCCI score ≤5 (75.4%), and mortality risk was associated with increasing score. The HRs for Q2 (score 3), Q3 (scores 4-5), and Q4 (scores ≥6) were 1.46 (97.5% CI 1.06-1.99), 3.03 (97.5% CI 2.35-3.90), and 4.51 (97.5% CI 3.46-5.88), respectively. For the subgroup analysis, amiodarone was not associated with a significant difference compared with placebo for individuals in Q1-Q3; however, it was associated with an increase in death for those in Q4 (HR 1.50; 97.5% CI 1.03-2.18). ICD was associated with a significant reduction in death compared with placebo for individuals in Q1 and Q3 (HR 0.42; 97.5% CI 0.20-0.84 and HR 0.70; 97.5% CI 0.50-0.97, respectively) but not for those in Q2 or Q4. Interaction testing across subgroups suggested HTE for amiodarone (p = 0.07) and ICD (p = 0.08) versus placebo across mCCI quartiles. CONCLUSIONS: Increasing comorbidity burden was associated with HTE when evaluating amiodarone and ICD compared with placebo in the SCD-HeFT trial. Our results highlight the importance of enrolling diverse patient populations in clinical trials and considering the possibility of HTE when translating results to clinical practice.

Defining Clinically Important Difference in the Atrial Fibrillation Effect on Quality-of-Life Score.

Background The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire has recently been validated to measure the impact of atrial fibrillation on quality of life, but a clinically important difference in AFEQT score has not been well defined. Methods and Results To determine the clinically important difference in overall AFEQT (score range= 0 [worst] to 100 [best]) and selected subscales, we analyzed data in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry, a United States-based outpatient atrial fibrillation registry. AFEQT was assessed at baseline and 1 year in a subset of 1347 ORBIT-AF patients from 80 US sites participating in ORBIT-AF from June 2010 to August 2011. The mean change method was used to relate changes in 1-year AFEQT scores to clinically important changes in the physician assessment of European Heart Rhythm Association functional status (1 class improvement and separately 1 class deterioration). Clinically important differences and 95% CI corresponding to either a 1 European Heart Rhythm Association class improvement or deterioration were 5.4 (3.6-7.2) and -4.2 (-6.9 to -1.5) AFEQT points, respectively. Similarly, clinically important difference values were seen for a 1 European Heart Rhythm Association class improvement for the AFEQT subscales Activities of Daily Living and Symptoms: 5.1 (2.5-7.6) and 7.1 (5.3-9.0) AFEQT points, respectively. Conclusions Based on the anchor of 1 European Heart Rhythm Association class change, changes in AFEQT score of + or -5 points are clinically important changes in patients' health. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT01165710.

Association of sex, age and education level with patient reported outcomes in atrial fibrillation.

BACKGROUND: In atrial fibrillation (AF), there are known sex and sociodemographic disparities in clinical outcomes such as stroke. We investigate whether disparities also exist with respect to patient-reported outcomes. We explored the association of sex, age, and education level with patient-reported outcomes (AF-related quality of life, symptom severity, and emotional and functional status). METHODS: The PaTH AF cohort study recruited participants (N = 953) with an AF diagnosis and age ≥ 18 years across 4 academic medical centers. We performed longitudinal multiple regression with random effects to determine if individual characteristics were associated with patient-reported outcomes. RESULTS: Women reported poorer functional status (ß - 2.23, 95% CI: -3.52, - 0.94) and AF-related quality of life (ß - 4.12, 95% CI: -8.10, - 0.14), and higher symptoms of anxiety (ß 2.08, 95% CI: 0.76, 3.40), depression (ß 1.44, 95% CI: 0.25, 2.63), and AF (ß 0.29, 95% CI: 0.08, 0.50). Individuals < 60 years were significantly (p < 0.05) more likely to report higher symptoms of depression, anxiety, and AF, and poorer AF-related quality of life. Lack of college education was associated with reporting higher symptoms of AF (ß 0.42, 95% CI: 0.17, 0.68), anxiety (ß 1.86, 95% CI: 0.26, 3.45), and depression (ß 1.11, 95% CI: 0.15, 2.38), and lower AF-related quality of life (ß - 4.41, 95% CI: -8.25, - 0.57) and functional status. CONCLUSION: Women, younger adults, and individuals with lower levels of education reported comparatively poor patient-reported outcomes. These findings highlight the importance of understanding why individuals experience AF differently based on certain characteristics.

Impact of certified CME in atrial fibrillation on administrative claims.

OBJECTIVE: To determine whether changes in physician behavior associated with a continuing medical education (CME) activity on atrial fibrillation (AF) can be measured using an administrative claims database. STUDY DESIGN: A retrospective, analytical review of physician practice changes and AF patient- related healthcare utilization and costs derived from an administrative claims database was performed on a cohort of Humana health system physicians. METHODS: The Humana physicians participated in a specified CME activity on the management of patients with AF. Treatment patterns of these providers and clinical outcomes of a cohort of established AF patients were compared 6 months before and 6 months after physician participation in the AF CME activity. RESULTS: Analysis of administrative claims data from Humana providers who participated in an AF CME activity and their patients demonstrated a significant reduction in AF-related healthcare costs and utilization, including decreased length of stay. Humana providers, in addition to the other CME activity participants, demonstrated significant gains in knowledge of evidence-based care strategies when presented with real-world scenarios of patients with AF. CONCLUSIONS: The use of administrative claims data is an innovative way of measuring the effectiveness of CME. These observations support the need for further investigation into the drivers of change in patient outcomes that may be associated with CME activities, as well as the utility of healthcare claims data as a possible valid measure of the impact of CME on physician performance and patient outcomes.

Cost burden of cardiovascular hospitalization and mortality in ATHENA-like patients with atrial fibrillation/atrial flutter in the United States.

BACKGROUND: The ATHENA trial (A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter) demonstrated that dronedarone reduced the risk of cardiovascular (CV) hospitalization/death by 24% (P < 0.001) in patients with atrial fibrillation (AF) and atrial flutter (AFL). HYPOTHESIS: In order to estimate the cost savings associated with dronedarone use, we estimated the costs associated with CV hospitalizations and inpatient mortality in a large cohort of ATHENA-like patients. METHODS: In this retrospective analysis, we evaluated the cost of CV hospitalization/mortality in real-world ATHENA-like patients without heart failure and with employer-sponsored Medicare supplemental insurance in the United States. Patients similar to those in ATHENA (age > or = 70 years with AF/AFL and > or = 1 stroke risk factor, without heart failure) who were hospitalized between January 2, 2005, and January 1, 2007, were identified from the MarketScan databases from Thomson Reuters. Health care costs were evaluated during the 12 months following the index hospitalization. RESULTS: The analysis included 10 200 ATHENA-like patients. Hospitalization for CV causes occurred in 53.9% of patients, with a total of 6700 CV hospitalizations for fatal/nonfatal causes. The most common nonfatal causes of CV hospitalizations were AF/other supraventricular rhythm disorders (20.2% of all CV hospitalizations), congestive heart failure (CHF; 14.3%), and transient ischemic attack (TIA)/stroke (10.7%). Mean costs per CV hospitalization for nonfatal causes were $10,908. Inpatient deaths from CV causes occurred in 264 (2.6%) patients; the most common causes of CV inpatient death were intracranial/gastrointestinal hemorrhage (24.2% of CV deaths), TIA/stroke (17.0%), and CHF (15.9%). Mean hospitalization costs per CV inpatient death were $18,565. CONCLUSIONS: Health care costs associated with CV hospitalizations and inpatient deaths among ATHENA-like patients in the US are high. Novel antiarrhythmic therapies such as dronedarone, with the potential to reduce CV hospitalizations/mortality in similar patients, could decrease health care costs if adopted in clinical practice.

Post myocardial infarction, left ventricular dysfunction, and the expanding role of cardiac implantable electrical devices.

In patients post myocardial infarction (MI) at risk for fatal ventricular arrhythmias, cardiac implantable devices offer a means of preventive therapy that complements optimal pharmacologic therapy. In patients with depressed ejection fractions, prophylactic implantable cardioverter defibrillators (ICDs) significantly improve survival. The efficacy of ICDs in the primary prevention of sudden cardiac death in patients post MI has been examined in a number of major primary prevention trials. These trials demonstrated as much benefit as some secondary prevention trials, which were conducted in high-risk patients who already had a spontaneous sustained ventricular tachyarrhythmia. In patients who are candidates for an ICD, best medical therapy for left ventricular dysfunction should be in place for some time before implanting. This waiting period could mean avoiding the implantation of a device in a patient who would heal sufficiently with pharmacologic therapy alone. In New York Heart Association (NYHA) class III and IV, patients with heart failure, and QRS intervals > or = 120 ms, cardiac resynchronization therapy (CRT) in combination with a defibrillator is a valuable addition to optimal pharmacologic therapy. Recent studies have demonstrated improved survival with CRT as well as improved quality of life. The high cost of cardiac implantable devices has led the Centers for Medicare and Medicaid Services to impose strict indications for use. However, it is likely that indications will be broadened for ICDs to include selected patients with left ventricular ejection fraction up to 40%, compared with the current indication of < or = 30%. Implanted devices must be followed up appropriately, with periodic interrogation and program adjustment to reduce the risk for pacing-induced desynchronization and to optimize hemodynamic benefit.