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.
GLOSSARY
- AE=
- adverse event;
- ANCOVA=
- analysis of covariance;
- AUC=
- area under the curve;
- BP=
- blood pressure;
- CVD=
- cardiovascular disease;
- CGI=
- Clinical Global Impression;
- CI=
- confidence interval;
- DBP=
- diastolic blood pressure;
- ENCORE=
- Effects of Neupro on Cardiovascular Observations in Patients With RLS;
- EoM=
- end of maintenance;
- FAS=
- full analysis set;
- HR=
- heart rate;
- IRLS=
- International Restless Legs Syndrome Study Group;
- LS=
- least squares;
- PLM=
- periodic limb movements;
- PLMSAI=
- periodic limb movements in sleep arousal index;
- PLMI=
- periodic limb movements index;
- PLMS=
- periodic limb movements during sleep;
- PLMW=
- periodic limb movements during wakefulness preceding sleep onset;
- QoL=
- quality of life;
- RLS=
- restless legs syndrome;
- SBP=
- systolic blood pressure
Footnotes
Coinvestigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The article processing charge was paid by UCB Pharma.
Supplemental data at Neurology.org
- Received March 6, 2015.
- Accepted in final form January 28, 2016.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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