{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:03:46Z","timestamp":1789657426100,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prescription stimulant use among the United States' (US) older adult population is increasing, yet little is known about the cardiovascular safety profiles of the two major prescription stimulant classes, methylphenidate (MPD) and amphetamine (AMP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the hazard of major adverse cardiovascular (CV) events between new users of prescription MPD and AMP products in US older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed a new user comparative safety study from a 5% random sample of fee\u2010for\u2010service Medicare beneficiaries. Continuously enrolled beneficiaries (Parts A\/B\/D) aged \u2265\u200966\u2009years who initiated MPD or AMP (1\/1\/17\u201312\/31\/21) were included. We required a 1\u2010year washout before the first prescription claim (index date) and excluded those with contraindications based on diagnosis codes. The primary outcome was incident modified 4\u2010Point Major Adverse Cardiovascular Event (4\u2010P MACE), including acute myocardial infarction, stroke or transient ischemic attack, ventricular arrhythmia, or all\u2010cause mortality; secondary outcomes included all\u2010cause mortality and CV events (all MACE excluding death). We used a 1\u2010year follow up after index date that was censored at change in insurance coverage, therapeutic switch, addition of the comparator drug, or end of the study (12\/31\/21). Confounders included demographics, healthcare utilization indicators, comorbidities, and other medications. We used trimmed propensity scores (PS) to create stabilized inverse probability of treatment weights (IPTW) and Cox proportional hazard regression to estimate the effect of MPD vs. AMP initiation on the first occurrence of 4\u2010P MACE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 2526 Medicare beneficiaries initiating MPD (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091340, mean [SD] age\u2009=\u200976.7 [7.4] years, 54.3% female sex) or AMP (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091186, mean [SD] age\u2009=\u200972.3 [5.4] years, 60.6% female sex). After PS trimming and applying IPTW, the groups were well\u2010balanced based on absolute standardized mean differences. During 2021.6 person\u2010years follow up (MPD [1009.9\u2009years] vs. AMP [1011.8\u2009years]), 339 4\u2010P MACE events occurred (MPD [\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009280] vs. AMP [\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200959]), of which 225 were deaths (MPD [\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009192] vs. AMP [\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200933]), and 114 were CV events (MPD [\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200988] vs. AMP [\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200926]). In the primary analysis, MPD vs. AMP initiation was associated with an increased risk of 4\u2010P MACE (HR\u2009=\u20091.73, 95% CI [1.36, 2.19]). The secondary analysis showed a statistically significant increased risk of all\u2010cause mortality (HR\u2009=\u20092.20, 95% CI [1.62, 3.00]), but not adverse CV events (HR\u2009=\u20091.14, 95% CI [0.77, 1.67]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initiation of MPD vs. AMP among older adults was associated with an increase in the hazard of 4\u2010P MACE. Secondary analysis suggested that this increase was driven by all\u2010cause mortality as opposed to adverse CV events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70381","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:30:30Z","timestamp":1776673830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Cardiovascular Safety of Prescription Amphetamine and Methylphenidate Initiation Among Older Adult Medicare Beneficiaries"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1113-5934","authenticated-orcid":false,"given":"Noah","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice and Science College of Pharmacy, University of Kentucky  Lexington Kentucky 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