Systematic review of cardiovascular safety across Parkinson's treatments reporting that levodopa, ergot-derived dopamine agonists, entacapone, and selegiline are associated with cardiotoxic effects (orthostatic hypotension, arrhythmias, valvular abnormalities) while safinamide, non-ergot agonists,…

Offers clinically actionable safety information to guide drug selection, monitoring, and trial design in PD therapeutic development and patient stratification, though it provides limited mechanistic or disease-modifying insights for discovery research.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor dysfunction and a host of additional systemic manifestations. PD is managed via a broad range of pharmacological and procedural treatments aimed at ameliorating motor and nonmotor symptoms. As PD occurs with a high prevalence of cardiac comorbidities, investigation and awareness of the cardiac safety of this range of treatments are essential. This review aims to synthesize current consensus on the cardiotoxic risk associated with the most prevalent treatments for PD, including levodopa, catechol-O-methyltransferase inhibitors, dopamine agonists, monoamine oxidase inhibitors, deep brain stimulation, and electroconvulsive therapy. This systematic literature review was performed via PubMed and Google Scholar by using predefined, relevant terms such as "Parkinson's," "cardiotoxicities," and "treatment," and synthesizing information drawn from studies selected based on methodologic rigor, generalizability, relevance, and quality of data related specifically to cardiovascular outcomes. Agents including levodopa, ergot-based dopamine agonists, entacapone, and selegiline have been found to be associated with cardiotoxic side effects, including orthostatic hypotension, arrhythmias, and valvular abnormalities, while agents such as safinamide, non-ergot-based dopamine agonists, and opicapone show minimal evidence of cardiotoxicity. Procedural treatments such as electroconvulsive therapy and deep brain stimulation appear to convey minimal cardiac risk, though typical perioperative vigilance is still necessary for high-risk patients. Collectively, evidence supports individualized tailoring of PD treatment based on cardiac risk profiles of patients and underscores the need for additional research attention to better elucidate the mechanisms underlying these cardiotoxic effects.