DOI: 10.1097/01.NT.0000454998.70120.26
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Issn Print: 1533-7006
Publication Date: 2014/09/18
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Excerpt
Midodrine seems to improve important clinical outcomes in patients with symptomatic orthostatic hypotension and recurrent reflex syncope, though the quality of research on the drug's effectiveness is lacking, according to a new meta-analysis.
“Overall, the quality of the evidence supporting the results is low/moderate, which means that our confidence in the effect estimate is limited and the true effect may be substantially different,” the researchers reported.
Midodrine, which received fast-track approval in 1996, became the subject of controversy a decade later when the US Food and Drug Administration (FDA) threatened to withdraw the drug from the market because it said post-marketing studies to confirm the drug's clinical benefits had not been completed.
The FDA reversed course following an outcry from patients and prescribing physicians. Around the same time the agency reached an agreement with Shire — the pharmaceutical company that holds the new drug application for midodrine under the brand name ProAmatine — to carry out the post-marketing studies.
According to background information in the new meta-analysis, symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) — also known as neurally mediated syncope — “are two conditions that cause significant morbidity.”
Although the two conditions “differ from a pathophysiological point of view, the absence of an adequate vasoconstrictive response plays a central role in both,” the authors of the paper, published in the Aug. 22 online edition of Neurology, wrote. “Furthermore, these conditions overlap in a significant proportion of patients presenting to the emergency department for transient loss of consciousness.”
Midodrine hydrochloride, an alpha ladrenergic receptors agonist, is recommended for the treatment of SOH and RRS in most clinical practice guidelines, noted the researchers from the Hospital Aleman in Buenos Aires, Argentina. Even so, they noted, published evidence on the drug's effectiveness was less than ideal, relying on surrogate markers to determine effect. The drug had been approved by the FDA under an accelerated approval process for drugs that treat serious or life-threatening illnesses.
“Although an optimal assessment of the evidence addressing midodrine's potential benefits requires evaluation of its effects on symptoms and side effects, most of the trials have focused on surrogate outcomes such as changes in blood pressure, heart rate or laboratory studies (tilt test),” lead author Ariel Izcovich, MD, and his team wrote.
“Four recently published systematic reviews evaluating midodrine for the treatment of SOH or vasovagal syncope failed to adequately assess all the existing evidence.
