Cost-Effectiveness of Oral Anticoagulants for Ischemic Stroke Prophylaxis Among Nonvalvular Atrial Fibrillation Patients
In this study by Shah et al, the authors used a Markov model to estimate the cost-effectiveness of all commercially available anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) for ischemic stroke prophylaxis in patients with atrial fibrillation from the perspective of a private payer. The distribution of stroke risk factors and age used in the model was obtained from a cohort of commercially insured patients and the rates of treatment-specific events from the relevant clinical trials. The estimation was projected in a lifetime horizon, and adjusted-dose warfarin was used as the common reference. In the base analysis, warfarin was the least costly and least effective with 9.02 quality-adjusted life years, whereas apixaban the most effective (9.38 quality-adjusted life years) and rivaroxaban the least cost-effective. Compared with warfarin, apixaban had the lowest incremental cost-effectiveness ratio ($25 816), making it the most cost-effective among the new oral anticoagulants. It should be noted, however, that the quality-adjusted survival benefit of apixaban (most effective new oral anticoagulant) was only marginally higher than that of rivaroxaban (least effective new oral anticoagulant), calculated at 50 days only. Additionally, in a hypothetical higher-risk population (congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke [CHADS2] score ≥3), the cost-effectiveness ratio favors dabigatran over apixaban because of its superior performance in ischemic stroke prevention. It follows that the cost-effectiveness of anticoagulants in ischemic stroke prevention is not necessarily a straightforward determination: it largely depends on the demographic characteristics and comorbidities of the insured population, the actual event rates, and drug pricing. See p 1555.
White Matter Hyperintensities Are Under Strong Genetic Influence
In this interesting study, Sachdev et al explored the genetic influence on white matter hyperintensities (WMH) using data from the Older Australian Twins Study, a population-based study of elderly twins in Eastern Australia. A total of 160 pairs (92 monozygotic and 68 dizygotic) of twins >65 years were included in this analysis. Heritability estimates were high (76%) for total WMH, as well as periventricular (64%) and deep (77%) WMHs, which shared a significant degree of genetic variance (68%). However, there is significant heterogeneity in WMH volume heritability in different brain regions, ranging from 76% in the occipital region to 18% in the cerebellum. Significant between-sex heterogeneity was also found in this study: heritability was consistently higher for women across cerebral regions, deep and periventricular WMHs, mirroring prior findings from the Framingham Heart Study. Additionally, there was a reduction of heritability with age for deep WMH, especially after the age of 75, whereas age had negligible effect on periventricular WMH heritability. Taken together these findings suggest that although WMHs in general are under a strong genetic influence, environmental (more precisely, nongenetic) factors might be more strongly implicated in WMH pathogenesis in men; similarly, the lesser degree of heritability of periventricular WMHs suggests that their underlying pathogenesis is different, more multifactorial than that of deep WMHs. See p 1422.
Recanalization Modulates Association Between Blood Pressure and Functional Outcome in Acute Ischemic Stroke
In this single-center retrospective study, Sargento-Freitas et al explored the effect of recanalization on the association between blood pressure in the acute phase (first 24 hours) of stroke and 3-month functional outcome. Six hundred seventy-four consecutive patients treated for acute ischemic stroke between 2009 and 2015 were included. The majority of them (663) received intraventricular tissue-type plasminogen activator, with only a small fraction (52) undergoing endovascular procedures. Recanalization status was determined with angiography at the end of the endovascular procedure or with transcranial Doppler or computed tomography angiography at 6 hours post stroke. Fifty-three percent of the patients achieved vessel recanalization. In multivariate analyses, the authors found a J-shaped relationship between blood pressure in the first 24-hour and 3-month outcome across the entire group. The same J-shaped relationship was maintained in the nonrecanalized group, whereas a linear relationship was identified in the recanalized group. Despite the limitations of the study (retrospective, single-center cohort, heterogeneous modalities used to assess recanalization, no measurement of collateral status, nonblinded 3-month functional status assessment), the findings are of interest. They suggest that regardless of recanalization status, higher blood pressure values confer a risk for worse outcome, which is likely mediated by a higher likelihood for symptomatic intracerebral hemorrhage. For those who do not achieve recanalization, there is probably a sweet spot, roughly between 120 and 140 mm Hg, that is associated with more favorable functional outcome, though the study only examines the first 24 hours after stroke. Intuition suggests that even in nonrecanalized patients, the shape of the curve of the blood pressure–functional outcome association might change over the first few days after stroke, becoming more linear, but this remains to be addressed in subsequent studies. See p 1571.
- © 2016 American Heart Association, Inc.