A study published in found that midodrine use was associated with fewer emergency department (ED) visits in heart failure patients with reduced ejection fraction (HFrEF). Frontiers of pharmacology. However, in these patients, it was also associated with an increased risk of respiratory failure, longer length of stay in the intensive care unit (ICU), increased hospitalization, and increased mortality.

These findings are based on a large study that included a total of 11,626 patients with HFrEF and left ventricular ejection fraction (LVEF) less than 50% without malignancy, non-dialysis dependence, or non-orthostatic hypotension. ing. Over the 10-year enrollment period from 2013 to his 2023, half of the group (n = 5813) received midodrine and the other half received no intervention.

Doctor using stethoscope on patient’s heart | Photo Doctor using stethoscope on patient’s heart Image credit: Joyfotoliakid – Stock.adobe.com

Midodrine, a peripheral alpha-1 agonist and antihypertensive drug approved for the treatment of orthostatic hypotension, has historically been well tolerated with few side effects. However, one large study reported adverse events in 7.9% of 3,030 patients, with common problems including arrector pili muscle reaction, gastrointestinal disturbances, cardiovascular disease, and urinary retention. Although these problems can often be managed by reducing the dose of midodrine, the off-label use of midodrine for conditions such as intradialytic hypotension and hypotension associated with heart failure has raised concerns, particularly regarding mortality. . Studies have shown an association between the use of midodrine and increased mortality in various clinical settings, questioning previous assumptions about its safety and suggesting that the level of safety of midodrine for patients with HFrEF is remains unclear.

In the current study, HFrEF patients who took midodrine had a 21% higher risk of hospitalization, a 16% higher risk of respiratory failure, and a 14% higher risk of ICU admission compared to patients who did not take midodrine. These patients had a 9% higher all-cause mortality rate and were 5% more likely to experience cardiac arrest. Conversely, midodrine use was associated with a 23% reduction in her risk of an ED visit. The researchers observed similar patterns of risk in most subgroups.

In addition to delayed detection of deterioration in heart function, the increased mortality associated with midodrine use may be due to several other factors, researchers said. Midodrine overdose can cause severe hypertension and reflex bradycardia, which is particularly problematic for HF patients taking concurrent beta-blockers, where midodrine can induce peripheral vasoconstriction. This has raised concerns about ischemic events. Additionally, midodrine use is associated with the development of supine hypertension, especially at high doses, which is associated with an increased risk of all-cause mortality and cardiovascular events.

This study has some limitations. First, randomized controlled trials in patients with advanced HFrEF are difficult, but their retrospective and observational nature may introduce bias, the researchers said. Despite efforts to mitigate this through propensity score matching, potential unknown residual confounders may also influence the results, and although transition to oral midodrine typically occurs before hospital discharge, midodrine administration The lack of distinction between inpatients and outpatients at the time may have affected the comprehensiveness of the study. Moreover, not all of the hospitalization-related outcomes were solely attributable to his HFrEF.

“Theoretically, more frequent refills could indicate a more advanced condition, requiring consultation with a cardiologist,” the researchers said. “Emphasis should be placed on monitoring lower refill frequencies to avoid late detection of deterioration in cardiac function. Use of midodrine for hemodynamic support in GDMT [guideline-directed medical therapy] Further research is needed to strengthen the available evidence. ”

reference

Wu MJ, Chen CH, Tsai SF. Safety of midodrine in heart failure patients with reduced ejection fraction: a retrospective cohort study. front pharmacol. Published online March 5, 2024. doi:10.3389/fphar.2024.1367790