Is dabigatran cost effective compared with warfarin for stroke prevention in atrial fibrillation? A critically appraised topic.

BACKGROUND: Warfarin has provided protection against cardioembolic stroke in the setting of nonvalvular atrial fibrillation (NVAF) for the past 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States, promises to provide the same or better stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether grand-scale adoption of dabigatran will be cost effective. OBJECTIVE: To critically assess current evidence regarding the cost effectiveness of dabigatran for preventing stroke in patients with NVAF compared with warfarin. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. RESULTS: A cost-effectiveness analysis (CEA) that followed a hypothetical cohort of NVAF patients 65 years of age or older and CHADS2≥1 over their lifetime comparing dabigatran with adjusted-dose warfarin was reviewed. Assuming a willingness to pay a threshold of $50,000 per quality-adjusted life year (QALY), base case results favored high-dose (150 mg bid) dabigatran as a cost-effective alternative to warfarin. Sensitivity analysis asserted that the cost effectiveness of dabigatran improved if it could be obtained for ≤$13/d or if it was used in populations with high risk of stroke or intracranial hemorrhage. CONCLUSIONS: Dabigatran 150 mg bid ($12,286 per QALY) is a cost-effective alternative to International Normalized Ratio-adjusted warfarin for the prevention of ischemic stroke in patients 65 years of age or older with NVAF.

Do cannabinoids reduce multiple sclerosis-related spasticity?

BACKGROUND: The plant Cannabis sativa contains numerous cannabinoids, which are aromatic hydrocarbons that have central nervous system effects mediated through specific cannabinoid receptors. Some patients with multiple sclerosis (MS) report symptomatic relief from spasticity, pain, and other symptoms when using smoked cannabis, and small trials have suggested some symptomatic benefit. OBJECTIVE: Do cannabinoids improve spasticity in patients with MS? METHODS: We addressed the question through the development of a structured, critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content experts in the field of MS. Participants started with a clinical scenario and a structured question, devised search strategies, located and compiled the best evidence, performed a critical appraisal, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. RESULTS: The largest randomized, placebo-controlled trial of oral cannabinoid therapy detected no improvement for MS-related spasticity as measured by the Ashworth scale. However, subjective participant reports indicated improvement in spasticity (P = 0.01), spasms (P = 0.038), sleep quality (P = 0.025), and pain (P = 0.002) without detriment to depression, fatigue, irritability, or walk time. A second randomized controlled trial, which used subjective participant report as the primary outcome, revealed the same discrepancy between subjective and objective spasticity outcome measures. CONCLUSION: Randomized controlled trials have failed to confirm objective evidence for a beneficial effect of cannabinoids on MS-related spasticity. However, improvement in subjective assessments of spasticity and other related symptoms have been consistently noted, raising questions about the sensitivity and validity of current objective outcome instruments. Further research is warranted with regards to both outcome instrument development and the effects of cannabinoids on MS-related spasticity.