Stimulants Linked to Early Risk of CV Events in Elderly

Older adults prescribed a stimulant are at a higher risk for adverse cardiovascular events early, but that risk drops off with long-term use, according to the results of a new study.

The findings, say researchers, suggest that physicians prescribing stimulants, typically done off-label in the elderly, need to keep close tabs on their patients in the first month.  

“The risk for any cardiovascular event was actually highest in the first 30 days,” lead investigator Mina Tadrous, PharmD, PhD (University of Toronto, Canada),” told TCTMD. “Part of that is expected, but what we didn’t see was the long-term effect of those who remained on [stimulants]. We do believe there is some selection bias, where those who have a reaction right away—they might have increased heart rate—drop off the medication. We know that doctors will commonly give a short trial to patients, especially if they have long-term concerns, and we also think doctors are generally vigilant with these medications.”

Concerns about the cardiovascular safety of stimulants are not new, said Tadrous, with the drug class known to increase heart rate and systolic blood pressure. One meta-analysis showed that use of stimulants increased average heart rate by 5.7 beats per minute and systolic blood pressure by 2.0 mm Hg.

The drugs are most commonly used in children to combat attention deficit hyperactivity disorder (ADHD), yet the use of stimulants have been on the rise in older adults where they are used off-label for the treatment of depression, to aid in poststroke recovery, to increase appetite, to improve motor function, or to offset fatigue, said Tadrous. There are few studies, he said, examining the cardiovascular safety of stimulants in this inherently higher-risk patient population.

In a study published October 25, 2021, in JAMA Network Open, the researchers close the evidence gap by turning to several databases to assess exposure to one of several stimulants, including amphetamine, methylphenidate, lisdexamfetamine, or dextroamphetamine, between 2002 and 2016 in adults 65 years and older. The propensity-matched analysis included 6,457 older adults exposed to stimulants with 24,853 adults who were not prescribed a stimulant during the study period.

At 30 days, the risk of any cardiovascular event, which included an emergency department visit/hospitalization for MI, stroke/TIA, or ventricular arrhythmia, was higher among patients exposed to one of the simulants (HR 1.4; 95% CI 1.1-1.8). That risk was most pronounced with respect to ventricular arrhythmias (HR 3.0; 95% CI 1.1-8.7) and stroke/TIA (HR 1.6; 95% 1.1-2.1). With the composite endpoint, there was no difference in risk between the two groups at 180 and 365 days. Similarly, the risk of ventricular arrhythmia and stroke/TIA was not increased at 180 and 365 days. All-cause mortality, a secondary endpoint, was increased in the first 30 days among those exposed to a stimulant (HR 2.4; 95% CI 2.1-2.8), but that difference in risk was not observed in longer follow-up.  

The data, said Tadrous, suggests that once patients emerge safely through the acute phase, there doesn’t appear to be a long-term hazard.

“They can be safely used off-label,” he said. “I think the data suggests vigilance remains for the first 30 days as doctors follow-up with patients closely once they start these treatments. I have a feeling doctors are already doing that, but they should continue to do so. As drugs get older, we sometimes feel a little more comfortable with them, but with these drugs, we still have to respect their power and there is a risk that has to be closely monitored.”