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- Cowper, Patricia A., et al.
(författare)
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Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective : Results From the ARISTOTLE Randomized Clinical Trial
- 2017
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 2:5, s. 525-534
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial.OBJECTIVE To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system.DESIGN, SETTING, AND PARTICIPANTS This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011.INTERVENTIONS Apixaban therapy vs warfarin therapy.MAIN OUTCOMES AND MEASURES Within-trial resource use and costwere compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed.RESULTS Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$ 60; 95% CI, -$ 2728 to $ 2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($ 53 925 per quality-adjusted life year, with 98% likelihood of meeting a $ 100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon.CONCLUSIONS AND RELEVANCE Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness.
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| 2. |
- Desai, A. S., et al.
(författare)
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Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial
- 2017
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6591 .- 2380-6583. ; 2:1, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Consensus guidelines recommend the use of mineralocorticoid receptor antagonists (MRAs) for selected patients with symptomatic heart failure and reduced ejection fraction (HFrEF) to reduce morbidity and mortality; however, the use of MRAs in combination with other inhibitors of the renin-angiotensin-aldosterone system increases the risk of hyperkalemia. Objective: To determine whether the risk of hyperkalemia associated with use of MRAs for patients with HFrEF is reduced by sacubitril/valsartan in comparison with enalapril. Design, Setting, and Participants: The PARADIGM-HF (Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial randomly assigned 8399 patients with chronic HF, New York Heart Association class II to IV symptoms, and a left ventricular EF of 40% or less to treatment with enalapril 10 mg twice daily or sacubitril/valsartan 97/103 mg twice daily (previously known as LCZ696 [200 mg twice daily]) in addition to guideline-directed medical therapy. Use of MRAs was encouraged but left to the discretion of study investigators. Serum potassium level was measured at every study visit. The incidence of hyperkalemia (potassium level >5.5 mEq/L) and severe hyperkalemia (potassium level >6.0 mEq/L) among patients treated or not treated with an MRA at baseline and the risk of subsequent hyperkalemia for those newly treated with an MRA during study follow-up were defined in time-updated Cox proportional hazards models. Analyses were conducted between August 1 and October 15, 2016. Main Outcomes and Measures: Incident hyperkalemia and severe hyperkalemia. Results: In comparison with the 3728 patients (44.4% of enrolled participants [21.6% female]) not taking an MRA at baseline, the 4671 patients (55.6% [22.0% female]) taking an MRA tended to be younger, with a lower EF, lower systolic blood pressure, and more advanced HF symptoms. Among those taking an MRA at baseline, the overall rates of hyperkalemia were similar between treatment groups, but severe hyperkalemia was more common in patients randomly assigned to enalapril than to sacubitril/valsartan (3.1 vs 2.2 per 100 patient-years; HR, 1.37 [95% CI, 1.06-1.76]; P = .02). In analyses icluding patients who newly started taking MRAs during the PARADIGM-HF trial, severe hyperkalemia remained more common in those randomly assigned to enalapril than to those randomly assigned to sacubitril/valsartan (3.3 vs 2.3 per 100 patient-years; HR, 1.43 [95% CI, 1.13-1.81]; P = .003). Conclusions and Relevance: Among MRA-treated patients with symptomatic HFrEF, severe hyperkalemia is more likely during treatment with enalapril than with sacubitril/valsartan. These data suggest that neprilysin inhibition attenuates the risk of hyperkalemia when MRAs are combined with other inhibitors of the renin-angiotensin-aldosterone system in patients with HF. Trial Registration: clinicaltrials.gov Identifier: NCT01035255.
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| 6. |
- Själander, Sara, et al.
(författare)
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Assessment of Use vs Discontinuation of Oral Anticoagulation After Pulmonary Vein Isolation in Patients With Atrial Fibrillation
- 2017
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Ingår i: JAMA cardiology. - : American Medical Association. - 2380-6583 .- 2380-6591. ; 2:2, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Pulmonary vein isolation (PVI) is a recommended treatment for patients with atrial fibrillation, but it is unclear whether it results in a lower risk of stroke.OBJECTIVES: To investigate the proportion of patients discontinuing anticoagulation treatment after PVI in association with the CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65-74 years, sex category [female]) score, identify factors predicting stroke after PVI, and explore the risk of cardiovascular events after PVI in patients with and without guideline-recommended anticoagulation treatment.DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort studywas conducted using Swedish national health registries from January 1, 2006, to December 31, 2012, with a mean-follow up of 2.6 years. A total of 1585 patients with atrial fibrillation undergoing PVI from the Swedish Catheter Ablation Register were included, with information about exposure to warfarin in the national quality register Auricula. Data analysis was performed from January 1, 2015, to April 30, 2016.EXPOSURES: Warfarin treatment.MAIN OUTCOMES AND MEASURES: Ischemic stroke, intracranial hemorrhage, and death.RESULTS: In this cohort of 1585 patients, 73.0% were male, the mean (SD) age was 59.0 (9.4) years, and the mean (SD) CHA(2)DS(2)-VASc score was 1.5 (1.4). Of the 1585 patients, 1175 were followed up for more than 1 year after PVI. Of these, 360 (30.6%) discontinued warfarin treatment during the first year. In patients with a CHA(2)DS(2)-VASc score of 2 or more, patients discontinuing warfarin treatment had a higher rate of ischemic stroke (5 events in 312 years at risk [1.6% per year]) compared with those continuing warfarin treatment (4 events in 1192 years at risk [0.3% per year]) (P = .046). Patients with a CHA(2)DS(2)-VASc score of 2 or more or those who had previously experienced an ischemic stroke displayed a higher risk of stroke if warfarin treatment was discontinued (hazard ratio, 4.6; 95% CI, 1.2-17.2; P = .02 and hazard ratio, 13.7; 95% CI, 2.0-91.9; P = .007, respectively).CONCLUSIONS AND RELEVANCE: These findings indicate that discontinuation ofwarfarin treatment after PVI is not safe in high-risk patients, especially those who have previously experienced an ischemic stroke.
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