Background: Lisdexamfetamine is a prodrug of dextroamphetamine used to treat attention-deficit/hyperactivity disorder. Its cardiovascular effects require interpretation across age groups, exposure durations and study designs.
Objective: To synthesize cardiovascular findings in people with attention-deficit/hyperactivity disorder and healthy volunteers, distinguishing physiological changes from clinical events.
Methods: Searches were conducted in PubMed, Embase, Cochrane Library, Google Scholar, and SciELO for publications from January 2000 to March 15, 2026. Cardiovascular results were extracted by population, exposure, comparator, and assessment time. Human appraisal of the evidence was performed by all four authors. Findings were synthesized narratively without meta-analysis.
Results: A total of 21 reports were included. Direct cardiovascular results from 15 primary reports across 15 protocols were synthesized, accounting for overlapping participants. In a four-week adult trial, least-squares mean pulse changes were +2.8, +4.2, and +5.2 beats/min with 30, 50, and 70 mg/day, versus 0.0 with placebo. Cardiovascular adverse events occurred in 35/358 lisdexamfetamine recipients and 0/62 placebo recipients. Two adolescent trials reported mean pulse changes of +4.7 and +6.7 beats/min, versus +0.3 and +2.0 with placebo. The exploratory preschool study reported −0.8 beats/min, whereas the preschool extension reported +4.67 beats/min. In a 104-week uncontrolled pediatric study, last-on-treatment changes were +7.0 beats/min, +3.4 mmHg systolic, and +3.2 mmHg diastolic. Mean Fridericia-corrected QT (QTcF) findings varied; individual abnormalities, arrhythmia, and syncope were reported.
Conclusion: Lisdexamfetamine commonly increases mean pulse and blood pressure in selected trial populations, although responses vary across studies and individuals. Short trials and uncontrolled extensions cannot exclude rare events or cumulative cardiovascular risk. Heterogeneity and limitations in search documentation constrain the interpretation of this review.
Keywords: Attention Deficit Hyperactivity Disorder; Blood Pressure; Cardiovascular Safety; Electrocardiography; Heart Rate; Lisdexamfetamine; Systematic Review.
Citation: Rodrigues, M. S., Santos, K. A. S. M., Rafael, L. M., & Silva, A. C. B. R. (2026). Cardiovascular Effects and Safety of Lisdexamfetamine in Attention-Deficit/Hyperactivity Disorder and Healthy Volunteers: A Systematic Review. I J cardio & card diso; 7(3):1-9. DOI : https://doi.org/10.47485/2998-4513.1058