ADHD Treatment Linked to Higher Long-Term Risk for Stroke and Heart Failure

Adult patients receiving treatment for attention-deficit/hyperactivity disorder (ADHD) for the first time have an increased 10-year risk for stroke, heart failure, and a composite cardiovascular outcome, with a higher risk occurring with a higher dosage, according to a study in the Journal of the American College of Cardiology.

Researchers evaluated the long-term risk for acute coronary syndrome, stroke, and heart failure associated with treatment for ADHD. They used data from Danish nationwide health registers.

Participants were aged 18 years and older and claimed a first-time prescription for treatment of ADHD (methylphenidate, atomoxetine, lisdexamfetamine, dexamfetamine, or modafinil) from 1998 to 2020. For comparison, a matched population without ADHD and no claimed prescription for treatment of ADHD was included.

Exposure was defined as a claimed prescription 180 days before the beginning of follow-up, 1 year after an initial claim of an ADHD medication prescription. The 3 exposure groups were the following:

• Prior users (who discontinued treatment before start of follow-up)
• Less than 1 defined daily dose (DDD) per day
• 1 or more DDD per day

The 4 cardiovascular outcomes were acute coronary syndrome, stroke, heart failure, and a composite outcome that comprised each individual outcome.

The cohort included 73,264 adult first-time users of ADHD medications from 1998 to 2020. At baseline, 26,357 (36%) were prior users (42% women; median age, 30 years), 31,211 (43%) were on less than 1 DDD per day (47% women; median age, 31 years), and 15,696 (21%) were on 1 or more DDD per day (47% women; median age, 33 years). The control group included 145,456 individuals (45% women, median age, 31 years). The patients receiving treatment for ADHD were followed for a median of 6.5 years (Q1-Q3, 2.7-10 years).

In the comparison of individuals with 1 or more DDD per day with prior users, an association was observed for an increased 10-year risk for stroke (risk ratio [RR], 1.2; 95% CI, 1.0-1.5; number needed to harm [NNH], 258), heart failure (RR, 1.7; 95% CI, 1.3-2.2; NNH, 204), and the composite outcome (RR, 1.3; 95% CI, 1.1-1.5; NNH, 116), but not for acute coronary syndromes (RR, 1.1; 95% CI, 0.8-1.4).

In analysis that compared individuals with 1 or more DDD per day with those with less than 1 DDD per day, the RRs were 1.1 (95% CI, 0.8-1.3), 1.2 (95% CI, 1.0-1.4), 1.4 (95% CI, 1.0- 1.7), and 1.2 (95% CI, 1.0-1.4) for an association with 10-year risk for acute coronary syndromes, stroke, heart failure, and the composite outcome, respectively.

Participants with 1 or more DDD per day and less than 1 DDD per day had an increased 10-year risk for the composite outcome with RRs of 1.7 (95% CI, 1.5-1.9) and 1.4 (95% CI, 1.3-1.5), respectively, compared with the matched background population without ADHD.

Individuals who were aged older than 40 years and those who were concomitantly treated with psychopharmaceuticals or nonsteroidal anti-inflammatory drugs had the highest standardized 10-year absolute risk for stroke, heart failure, and composite outcome.

Limitations of the study include the lack of information in the registers on smoking, physical activity, eating habits, blood pressure, and heart rate. Also, exposure was not included continuously as a time-varying variable in the statistical analyses, and unmeasured confounding is possible.

“Greater attention to cardiovascular risk factors at initiation of treatment and to cardiovascular symptoms during treatment may be warranted in patients with ADHD, with particular focus on those taking a higher dosage for extended periods,” the researchers wrote.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on The Cardiology Advisor