Background: 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).
Objective: To compare the hazard of major adverse cardiovascular (CV) events between new users of prescription MPD and AMP products in US older adults.
Methods: We employed a new user comparative safety study from a 5% random sample of fee-for-service Medicare beneficiaries. Continuously enrolled beneficiaries (Parts A/B/D) aged ≥ 66 years who initiated MPD or AMP (1/1/17-12/31/21) were included. We required a 1-year washout before the first prescription claim (index date) and excluded those with contraindications based on diagnosis codes. The primary outcome was incident modified 4-Point Major Adverse Cardiovascular Event (4-P MACE), including acute myocardial infarction, stroke or transient ischemic attack, ventricular arrhythmia, or all-cause mortality; secondary outcomes included all-cause mortality and CV events (all MACE excluding death). We used a 1-year 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-P MACE.
Results: We identified 2526 Medicare beneficiaries initiating MPD (N = 1340, mean [SD] age = 76.7 [7.4] years, 54.3% female sex) or AMP (N = 1186, mean [SD] age = 72.3 [5.4] years, 60.6% female sex). After PS trimming and applying IPTW, the groups were well-balanced based on absolute standardized mean differences. During 2021.6 person-years follow up (MPD [1009.9 years] vs. AMP [1011.8 years]), 339 4-P MACE events occurred (MPD [N = 280] vs. AMP [N = 59]), of which 225 were deaths (MPD [N = 192] vs. AMP [N = 33]), and 114 were CV events (MPD [N = 88] vs. AMP [N = 26]). In the primary analysis, MPD vs. AMP initiation was associated with an increased risk of 4-P MACE (HR = 1.73, 95% CI [1.36, 2.19]). The secondary analysis showed a statistically significant increased risk of all-cause mortality (HR = 2.20, 95% CI [1.62, 3.00]), but not adverse CV events (HR = 1.14, 95% CI [0.77, 1.67]).
Conclusions: Initiation of MPD vs. AMP among older adults was associated with an increase in the hazard of 4-P MACE. Secondary analysis suggested that this increase was driven by all-cause mortality as opposed to adverse CV events.
Keywords: OIder adults; amphetamine; cardiovascular events; methylphenidate; mortality; prescription stimulants.
Use of prescription stimulants is growing among older adults in the United States, but we know little about how safe these medications are for the heart. This study looked at two commonly used stimulant types—methylphenidate (MPD) and amphetamine (AMP)—to see if one is linked to more heart‐related problems. Using data from Medicare, we studied people aged 66 and older who started taking either MPD or AMP between 2017 and 2021. We tracked serious heart events like heart attacks, strokes, irregular heartbeats, and all‐cause deaths. The study included over 2500 people and followed them for about a year. We found that those who started MPD had a 73% higher risk of these serious events compared to those who took AMP. Specifically, MPD users had a significantly higher chance of dying during the study period, while the difference in other heart‐related events was not as clear. These results suggest that starting MPD may carry more risk than starting AMP for older adults, especially when it comes to overall survival. Doctors and patients should consider these findings when choosing between these medications.
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