April Slee

Cost-effectiveness of rhythm versus rate control in atrial fibrillation.

Context Randomized trials show that rate control and rhythm control are similarly effective in the treatment of atrial fibrillation; therefore, economic issues will play a large role in the choice of therapy. Contribution This cost-effectiveness model shows that rate control saves costs compared with rhythm control. Implications From an economic perspective, unless specific clinical factors suggest a benefit of rhythm control for a particular patient, rate control seems to be the preferred strategy for the management of atrial fibrillation. Atrial fibrillation is the most common sustained type of cardiac arrhythmia treated by physicians. Its prevalence increases with advancing age, affecting approximately 5% of those 65 years of age and older and 10% of those older than 80 years of age (1-3). As the U.S. population ages, it is expected that more than 5 million persons will be living with atrial fibrillation by the year 2050 (4). Despite significant advances in the effectiveness of treatments for atrial fibrillation and its associated comorbid conditions, disability and mortality from atrial fibrillation remain high (5-10). The optimal approach to the rhythm management of atrial fibrillation remains unclear. There are 2 main approaches: Rhythm control uses electrical cardioversion, antiarrhythmic drugs, and, sometimes, nonpharmacologic therapies (for example, multisite atrial pacing, maze procedures, or radiofrequency ablation procedures) to maintain sinus rhythm; rate control uses atrioventricular nodal blocking agents (and, if needed, ablation of the atrioventricular junction and pacemaker implantation) for ventricular rate control. Recently, several randomized, controlled studies have compared rate control versus rhythm control. In the largest of these studies, investigators in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) randomly assigned 4060 patients with atrial fibrillation (mean age, 70 years) to either rate control or rhythm control (10-12). After a mean follow-up of 3.5 years, mortality did not differ significantly between the groups (hazard ratio for rate control vs. rhythm control, 0.87 [95% CI, 0.75 to 1.01]; P= 0.08), and the rate-control approach was associated with a lower risk for adverse drug effects (12). The results of the other large study were consistent with these findings (13). The RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study randomly assigned 522 patients with persistent atrial fibrillation after electrical cardioversion to either rhythm control or rate control; the mean follow-up was 2.3 years (13). Patients in both treatment groups received oral anticoagulant drugs. There was a nonsignificant trend toward reduced death or other serious cardiovascular events in patients treated by the rate-control strategy. Consequently, economic factors often play a substantial role in guiding treatment selection. Several authors have examined the incremental cost-effectiveness of rhythm-control versus rate-control strategies for treating atrial fibrillation; however, their studies have been confined to modeling exercises of hypothetical scenarios that lack data on efficacy and resource use from randomized trials (14, 15). This paper reports an economic analysis based on the results of AFFIRM. The objective was to estimate the incremental cost-effectiveness of rhythm-control versus rate-control strategies from AFFIRM. Methods AFFIRM Study Sample AFFIRM included 4060 patients with atrial fibrillation whose treatment was block randomized by center to be either rhythm control or rate control (12). Similar to patients with atrial fibrillation in the general population, most of the patients in AFFIRM were older men (men represented 61% of the sample) with common associated cardiovascular comorbid conditions (history of hypertension [71%], coronary artery disease [39%], and congestive heart failure [9%]). The mean age (SD) for all patients was 69.7 9.0 years, and 75% were 65 years of age or older. The qualifying event was the first episode of atrial fibrillation in 34% of patients and recurrent atrial fibrillation in the remaining 66% of patients. The overriding principles for enrollment of patients in AFFIRM were based on the clinical judgment of the investigator and were as follows: Atrial fibrillation was likely to be recurrent, atrial fibrillation was likely to cause morbidity or death, long-term treatment for atrial fibrillation was warranted, anticoagulation was not contraindicated, the patient was eligible for at least 2 drug trials in both treatment strategies, and treatment in both strategies could be initiated immediately after randomization. Additional information on the design, inclusion and exclusion criteria, and results of AFFIRM are available elsewhere (10-12). The economic analysis described here compares costs and effects of the 2 management strategies among patients enrolled in AFFIRM from the perspective of a third-party payer. The outcome was the incremental cost-effectiveness ratio comparing rhythm control and rate control, measured in dollars per life-year gained. Survival We obtained data on survival from the time of randomization to the end of study follow-up and use of specific health care resources for all 4060 AFFIRM patients. For patients who were lost to follow-up, withdrew from the study, or had incomplete follow-up, all available data were included in the analysis. Patients were censored at withdrawal or loss to follow-up. We derived the within-study mean survival time for each treatment group by using the KaplanMeier product limit estimator to account for censoring during follow-up (16). To obtain an unbiased estimate of mean survival, exposure was truncated at 5.65 years, which was the longest follow-up observed in AFFIRM (17). Resource Use and Costs We estimated costs by multiplying the number of each resource used by its unit cost (18). All unit costs for resources were estimated in U.S. dollars for the year 2002. Price estimates from earlier years were adjusted by applying the Consumer Price Index, Medical Care component (19). For each measure of resource use, 3 different unit costs were derived and considered in separate analyses: a base case for the most likely scenario, a low estimate, and a high estimate. The analysis considered costs of all hospitalizations, cardiac procedures, cardioversion, short-stay and emergency department visits, and medications used to treat atrial fibrillation from the perspective of a third-party payer. Hospital Costs At each follow-up visit during the study, the total number of hospitalized days since the last visit was recorded, along with the primary reason (cardiovascular or noncardiovascular cause) for hospitalization. The mean cost per hospital day was estimated from the Healthcare Cost and Utilization Project (HCUP) statistics for the 1995 HCUP-3 Nationwide Inpatient Sample (20) for Diseases of the Circulatory System, excluding any diagnosis associated with a mean patient age of younger than 18 years, for cardiovascular and noncardiovascular causes. The low and high estimates of the per diem for hospital days were based on the 25th and 75th percentile of mean charges, respectively. The HCUP prices were adjusted to represent costs by using a cost-to-charge ratio of 0.575, which is based on the 2002 estimate from the Centers for Medicare & Medicaid Services (21). In addition, physician charges for subsequent hospital care as a level II visit (Current Procedural Terminology [CPT] [22] code 99232) were applied for each hospital day recorded. In the base case, an average estimate for the physician fee payment for this CPT code was calculated from the 2002 Physician Fee Schedule Payment Amount File National/Carrier for facility-based procedures for all carriers and localities listed in the database (23). In the sensitivity analysis, we used the minimum physician fee across carriers and localities for each procedure as the low cost estimate. We based the high cost estimate on the standard billed charge from the Marshfield Clinic, an ambulatory care facility in Marshfield, Wisconsin. This clinical center recruited most patients in the study and provides an estimate of charges for centers in the United States. Although these estimates are based on data from 1 facility, they are a reasonable estimate for the high-cost scenario, in between billed charges from a teaching hospital and a private clinic. Costs of Cardiac Procedures At each follow-up visit during the study, the number of cardiac procedures (percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, pacemakers, valve surgery, ablation) performed since the previous follow-up visit was recorded. No information was available from AFFIRM to describe the number of arteries revascularized during percutaneous transluminal coronary angioplasty interventions or coronary artery bypass graft surgeries. We assumed that only 1 lesion was treated for each percutaneous transluminal coronary angioplasty procedure. We estimated the number of arteries revascularized during bypass surgery as a weighted average from the National Hospital Discharge Survey (NHDS) data set for 2000 (24, 25). We included the costs of the most frequent cardiac procedures in the analysis. Hospital costs include the costs of all facility personnel except physicians. Physician costs consisted of a physician fee for diagnostic and therapeutic procedures, as well as any applicable anesthesia fee. Perfusionist fees for open-heart cardiac procedures were not included because these costs are included in the hospital costs. The analysis included costs for pacemakers and implantable cardioverter defibrillators (ICDs) because they have high unit cost (24, 25). In the base case, the hardware cost (that is, device and electrode or electrodes costs) for the most widely used single-chamber and dual-chamber device was assigned on the

Relationship of Apolipoproteins A-1 and B, and Lipoprotein (a) to Cardiovascular Outcomes in the AIM-HIGH Trial

OBJECTIVES This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. BACKGROUND Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. METHODS Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. RESULTS Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.

Relationship of Lipoproteins to Cardiovascular Events The AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes)

OBJECTIVES This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial. BACKGROUND During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)-lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone. METHODS Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤ 150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. RESULTS CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥ 198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group. CONCLUSIONS Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C-lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289).

Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes).

OBJECTIVES This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. BACKGROUND Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. METHODS Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. RESULTS Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.

Relationship of Lipoproteins to Cardiovascular Events in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) Trial

OBJECTIVES This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial. BACKGROUND During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)-lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone. METHODS Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤ 150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. RESULTS CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥ 198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group. CONCLUSIONS Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C-lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289).

Cardiovascular Outcomes in the AFFIRM Trial (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) An Assessment of Individual Antiarrhythmic Drug Therapies Compared With Rate Control With Propensity Score-Matched Analyses

OBJECTIVES The impact of individual antiarrhythmic drugs (AADs) on mortality and hospital stay in atrial fibrillation (AF) was evaluated. BACKGROUND Cardiovascular (CV) outcomes in AF patients receiving pharmacologic rhythm control therapy have not been compared with rate control therapy on the basis of AAD selection. METHODS We compared CV outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial in subgroups defined by the initial AAD selected with propensity score matched subgroups from the rate arm (Rate). RESULTS Seven hundred twenty-nine amiodarone patients, 606 sotalol patients, and 268 Class 1C patients were matched. The composite outcome of mortality or cardiovascular hospital stays (CVH) showed better outcomes with Rate compared with amiodarone (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.03 to 1.36, p = 0.02), sotalol (HR: 1.32, 95% CI: 1.13 to 1.54, p < 0.001), and Class 1C (HR: 1.22, 95% CI: 0.97 to 1.56, p = 0.10). There was a nonsignificant increase in mortality with amiodarone (HR: 1.20, 95% CI: 0.94 to 1.53, p = 0.15) with the risk of non-CV death being significantly higher with amiodarone versus Rate (HR: 1.11, 95% CI: 1.01 to 1.24, p = 0.04). First CVH event rates at 3 years were 47% for amiodarone, 50% for sotalol, and 44% for Class 1C versus 40%, 40%, and 36%, respectively, for Rate (amiodarone HR: 1.20, 95% CI: 1.03 to 1.40, p = 0.02, sotalol HR: 1.364, 95% CI: 1.16 to 1.611, p < 0.001, Class 1C HR: 1.24, 95% CI: 0.96 to 1.60, p = 0.09). Time to CVH with intensive care unit stay or death was shorter with amiodarone (HR: 1.22, 95% CI: 1.02 to 1.46, p = 0.03). CONCLUSIONS In AFFIRM, composite mortality and CVH outcomes differed for Rate and AADs due to differences in CVH; CVH event rates during follow-up were high for all cohorts, but they were higher for all groups on AADs. Death, intensive care unit hospital stay, and non-CV death were more frequent with amiodarone.

Cardiovascular Outcomes in the AFFIRM Trial (Atrial Fibrillation Follow-Up Investigation of Rhythm Management)

OBJECTIVES The impact of individual antiarrhythmic drugs (AADs) on mortality and hospital stay in atrial fibrillation (AF) was evaluated. BACKGROUND Cardiovascular (CV) outcomes in AF patients receiving pharmacologic rhythm control therapy have not been compared with rate control therapy on the basis of AAD selection. METHODS We compared CV outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial in subgroups defined by the initial AAD selected with propensity score matched subgroups from the rate arm (Rate). RESULTS Seven hundred twenty-nine amiodarone patients, 606 sotalol patients, and 268 Class 1C patients were matched. The composite outcome of mortality or cardiovascular hospital stays (CVH) showed better outcomes with Rate compared with amiodarone (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.03 to 1.36, p = 0.02), sotalol (HR: 1.32, 95% CI: 1.13 to 1.54, p < 0.001), and Class 1C (HR: 1.22, 95% CI: 0.97 to 1.56, p = 0.10). There was a nonsignificant increase in mortality with amiodarone (HR: 1.20, 95% CI: 0.94 to 1.53, p = 0.15) with the risk of non-CV death being significantly higher with amiodarone versus Rate (HR: 1.11, 95% CI: 1.01 to 1.24, p = 0.04). First CVH event rates at 3 years were 47% for amiodarone, 50% for sotalol, and 44% for Class 1C versus 40%, 40%, and 36%, respectively, for Rate (amiodarone HR: 1.20, 95% CI: 1.03 to 1.40, p = 0.02, sotalol HR: 1.364, 95% CI: 1.16 to 1.611, p < 0.001, Class 1C HR: 1.24, 95% CI: 0.96 to 1.60, p = 0.09). Time to CVH with intensive care unit stay or death was shorter with amiodarone (HR: 1.22, 95% CI: 1.02 to 1.46, p = 0.03). CONCLUSIONS In AFFIRM, composite mortality and CVH outcomes differed for Rate and AADs due to differences in CVH; CVH event rates during follow-up were high for all cohorts, but they were higher for all groups on AADs. Death, intensive care unit hospital stay, and non-CV death were more frequent with amiodarone.

Metabolic Syndrome in Adults With Congenital Heart Disease

Background Metabolic syndrome increases risk for atherosclerotic coronary artery disease, and its prevalence increases with increasing age and body mass index. Adults with congenital heart disease (ACHD) are now living longer and accruing coronary artery disease risk factors. However, the prevalence of metabolic syndrome in ACHD patients is unknown. Methods and Results We conducted a retrospective cohort study of ACHD patients at our center to quantify the prevalence of metabolic syndrome in an ACHD population. Using case‐control matching, we constructed a comparable control group from a population‐based sample of 150 104 adults. International Diabetes Federation criteria were used to define metabolic syndrome. We used logistic regression to compare the risk of metabolic syndrome across the resulting cohorts, which were composed of 448 ACHD patients and 448 controls matched by age and sex. Mean age of both groups was 32.4±11.3 years, and 51.3% were female. Obesity was present in 16.1% of the ACHD patients and 16.7% of the controls. Metabolic syndrome was more common in ACHD patients than in controls (15.0% versus 7.4%; odds ratio 1.82, 95% CI 1.25–2.65). Conclusions Our data suggest that metabolic syndrome is more common among adults with congenital heart disease than in the general population. Thus, patients with congenital heart disease should be screened for metabolic syndrome and risk factors mitigated where possible to prevent atherosclerotic coronary artery disease. Preventive cardiology should be included during routine ACHD care.

Relationship of apolipoproteins A-1 and b, and lipoprotein(a) to cardiovascular outcomes

OBJECTIVES This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. BACKGROUND Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. METHODS Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. RESULTS Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.

Cardiovascular Outcomes in the AFFIRM Trial: An Assessment of Individual Antiarrhythmic Drug Therapies compared to Rate Control Using Propensity Score Matched Analyses

OBJECTIVES The impact of individual antiarrhythmic drugs (AADs) on mortality and hospital stay in atrial fibrillation (AF) was evaluated. BACKGROUND Cardiovascular (CV) outcomes in AF patients receiving pharmacologic rhythm control therapy have not been compared with rate control therapy on the basis of AAD selection. METHODS We compared CV outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial in subgroups defined by the initial AAD selected with propensity score matched subgroups from the rate arm (Rate). RESULTS Seven hundred twenty-nine amiodarone patients, 606 sotalol patients, and 268 Class 1C patients were matched. The composite outcome of mortality or cardiovascular hospital stays (CVH) showed better outcomes with Rate compared with amiodarone (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.03 to 1.36, p = 0.02), sotalol (HR: 1.32, 95% CI: 1.13 to 1.54, p < 0.001), and Class 1C (HR: 1.22, 95% CI: 0.97 to 1.56, p = 0.10). There was a nonsignificant increase in mortality with amiodarone (HR: 1.20, 95% CI: 0.94 to 1.53, p = 0.15) with the risk of non-CV death being significantly higher with amiodarone versus Rate (HR: 1.11, 95% CI: 1.01 to 1.24, p = 0.04). First CVH event rates at 3 years were 47% for amiodarone, 50% for sotalol, and 44% for Class 1C versus 40%, 40%, and 36%, respectively, for Rate (amiodarone HR: 1.20, 95% CI: 1.03 to 1.40, p = 0.02, sotalol HR: 1.364, 95% CI: 1.16 to 1.611, p < 0.001, Class 1C HR: 1.24, 95% CI: 0.96 to 1.60, p = 0.09). Time to CVH with intensive care unit stay or death was shorter with amiodarone (HR: 1.22, 95% CI: 1.02 to 1.46, p = 0.03). CONCLUSIONS In AFFIRM, composite mortality and CVH outcomes differed for Rate and AADs due to differences in CVH; CVH event rates during follow-up were high for all cohorts, but they were higher for all groups on AADs. Death, intensive care unit hospital stay, and non-CV death were more frequent with amiodarone.