Effects of angiotensin type 1 receptor antagonists on Parkinson's disease progression: An exploratory study in the PPMI database.

INTRODUCTION: We explored the potential clinical effects of angiotensin-II AT1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) in patients from the Parkinson's Progress Marker Initiative (PPMI) study database. METHODS: We included 423 newly diagnosed PD patients, free from antiparkinsonian treatment, from the PPMI. We compared the proportion of patients starting on l-DOPA during the first year of follow-up, and the changes in MDS-UPDRS total score and sub-scores during the first five follow-up years for patients exposed or not to ARBs or ACEIs. RESULTS: Treatment with ARBs did not affect the proportion of patients on l-DOPA during the first year (adjusted OR, 95% CI = 0.26, 0.03-2.18, N.S.) while reduced MDS-UPDRS total score (0.85, 0.76-0.95, p < 0.01). Patients treated with ACEIs experienced no changes in either measure. CONCLUSIONS: These results show potential signals for a beneficial effect with ARBs. Further clinical trials are warranted.

Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.

Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and -7.8 (-44.3, 28.8) kg/m2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis. TRIAL REGISTRATION: ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002.