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Use of medications for attention deficit-hyperactivity disorder (ADHD) was not associated with increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis of 19 studies showed, although the researchers cautioned that a modest risk increase could not be completely ruled out.

Among over 3 million people, there were no statistically significant associations between ADHD medication use and any CVD risks among children and adolescents (relative risk [RR] 1.18, 95% CI 0.91-1.53), young or middle-age adults (RR 1.04, 95% CI 0.43-2.48), or older adults (RR 1.59, 95% CI 0.62-4.05) over a median follow-up ranging from 0.25 to 9.5 years, reported Le Zhang, MPH, of the Karolinska Institutet in Stockholm, and co-authors.

When looking at specific cardiovascular outcomes, there were no statistically significant associations between use of ADHD medications and cardiac arrest or arrhythmias (RR 1.60, 95% CI 0.94-2.72), cerebrovascular diseases (RR 0.91, 95% CI 0.72-1.15), or myocardial infarction (RR 1.06, 95% CI 0.68-1.65), they noted in .

Zhang and team also found no statistically significant associations for stimulants (RR 1.24, 95% CI 0.84-1.83) or nonstimulants (RR 1.22, 95% CI 0.25-5.97).

"Overall, our meta-analysis provides reassuring data on the putative cardiovascular risk with ADHD medications," they wrote.

While there were also no associations between use of ADHD medications and any CVD in people with pre-existing CVD (RR 1.31, 95% CI 0.80-2.16) and in women (RR 1.88, 95% CI 0.43-8.24), Zhang and co-authors noted that the point estimates were higher when compared to those without pre-existing and for women versus men. They said further research is needed to determine possible associations in these groups.

Similarly, they said that they could not rule out the possibility of a modest risk increase of some CVDs, such as cardiac arrest or tachyarrhythmias, with use of ADHD medications.

"In clinical practice, specific individuals with ADHD might be particularly prone to negative cardiovascular outcomes," Zhang and team wrote. "Therefore, clinicians should discuss with their patients and families the possible cardiovascular risk of ADHD medication in light of the latest evidence, and they should rigorously follow clinical guidelines that suggest monitoring of blood pressure and heart rate at baseline and each medication review."

In , Roy C. Ziegelstein, MD, of Johns Hopkins University School of Medicine in Baltimore, noted that the study's findings "should make us question whether these medications -- which have raised understandable concern about CVD risk in the past -- may actually be safe in this regard."

"The truth is, we have been wrong before with respect to medications and CVD risk, often in the other direction," he added, highlighting the use of two antiarrhythmic drugs -- encainide and flecainide -- for myocardial infarction survivors, which were later found to increase the risk of death from arrhythmias.

"Healthcare professionals must exercise caution and not slavishly adhere to consensus guidelines or follow conclusions from meta-analyses when treating individual patients," he concluded. While these data are "reassuring in many ways, healthcare professionals must carefully weigh these factors when prescribing ADHD medications, especially to older adults, individuals with established CVD, and those with other comorbidities that increase CVD risk."

For this systematic review and meta-analysis, Zhang and colleagues included 19 studies published from 2007 to 2021, which included 3,931,532 participants, including children, adolescents, and adults (60.9% male) from six countries or regions (U.S., South Korea, Canada, Denmark, Spain, and Hong Kong). Most were cohort studies (n=14), and the median follow-up time ranged from 0.25 to 9.5 years (median 1.5 years).

Zhang and team acknowledged that "heterogeneity was high and significant for most analyses," which was the study's main limitation. They also noted that they could not compare the associations of CVD with specific ADHD medications, or analyze dose-response associations.

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