Rotigotine's effect on PLM-associated blood pressure elevations in restless legs syndrome: An RCT

Neurology. 2016 May 10;86(19):1785-93. doi: 10.1212/WNL.0000000000002649. Epub 2016 Apr 13.

Abstract

Objective: This double-blind, placebo-controlled, interventional trial was conducted to investigate the effects of rotigotine patch on periodic limb movement (PLM)-associated nocturnal systolic blood pressure (SBP) elevations.

Methods: Patients with moderate to severe restless legs syndrome (RLS) were randomized to rotigotine (optimal dose [1-3 mg/24 h]) or placebo. Continuous beat-to-beat blood pressure (BP) assessments were performed during polysomnography at baseline and at the end of 4-week maintenance. Primary outcome was change in number of PLM-associated SBP elevations (defined as slope of linear regression ≥2.5 mm Hg/beat-to-beat interval over 5 consecutive heartbeats [≥10 mm Hg]). Additional outcomes were total SBP elevations, PLM-associated and total diastolic BP (DBP) elevations, periodic limb movements index (PLMI), and PLM in sleep arousal index (PLMSAI).

Results: Of 81 randomized patients, 66 (37 rotigotine, 29 placebo) were included in efficacy assessments. PLM-associated SBP elevations were significantly reduced with rotigotine vs placebo (least squares mean treatment difference [95% confidence interval (CI)] -160.34 [-213.23 to -107.45]; p < 0.0001). Rotigotine-treated patients also had greater reduction vs placebo in total SBP elevations (-161.13 [-264.47 to -57.79]; p = 0.0028), PLM-associated elevations (-88.45 [-126.12 to -50.78]; p < 0.0001), and total DBP elevations (-93.81 [-168.45 to -19.16]; p = 0.0146), PLMI (-32.77 [-44.73 to -20.80]; p < 0.0001), and PLMSAI (-7.10 [-11.93 to -2.26]; p = 0.0047). Adverse events included nausea (rotigotine 23%; placebo 8%), headache (18% each), nasopharyngitis (18%; 8%), and fatigue (13%; 15%).

Conclusions: Further investigation is required to determine whether reductions in nocturnal BP elevations observed with rotigotine might modify cardiovascular risk.

Classification of evidence: This study provides Class I evidence that for patients with moderate to severe RLS, rotigotine at optimal dose (1-3 mg/24 h) reduced PLM-associated nocturnal SBP elevations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Blood Pressure Determination
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / adverse effects
  • Double-Blind Method
  • Heart Rate / drug effects
  • Humans
  • Least-Squares Analysis
  • Middle Aged
  • Nocturnal Myoclonus Syndrome / complications
  • Nocturnal Myoclonus Syndrome / drug therapy*
  • Nocturnal Myoclonus Syndrome / physiopathology
  • Photoperiod
  • Polysomnography
  • Restless Legs Syndrome / complications
  • Restless Legs Syndrome / drug therapy
  • Restless Legs Syndrome / physiopathology*
  • Severity of Illness Index
  • Tetrahydronaphthalenes / administration & dosage*
  • Tetrahydronaphthalenes / adverse effects
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects
  • Transdermal Patch / adverse effects
  • Treatment Outcome
  • Young Adult

Substances

  • Dopamine Agonists
  • Tetrahydronaphthalenes
  • Thiophenes
  • rotigotine