Medical expulsive therapy or bust?

Whether or not medical expulsive therapy (MET) is a sound recommendation for patients with kidney or ureteral stones is a matter of debate. MET still has a role in the management of some patients, according to AUA guidelines for the management of ureteral calculi. But a large, multicenter study in The Lancet (2015; 386:341–9) found no evidence supporting the use of MET with the alpha-blocker tamsulosin or the calcium channel blocker nifedipine. The lead author of that study told Urology Times that, based on the results, these drugs should no longer be recommended or used to reduce the risk of intervention required to remove stones in people with ureteric colic.

Related: New study supports MET for larger ureteric stones

So, what is a urologist to do? We asked two experts in stone disease to answer the important questions regarding MET use in this patient population. The experts are Stephen Y. Nakada, MD, professor and chairman of urology at the University of Wisconsin School of Medicine and Public Health in Madison, and Glenn M. Preminger, MD, professor and chief of urologic surgery at Duke University Medical Center, Durham, NC.

Dr. Preminger helped to write the AUA’s guidelines on ureteral calculi management. Neither physician has conflicts of interest related to this topic.

Why the recent controversy?

In a recent study, researchers at the University of Michigan Medical School reviewing 55 kidney stone studies found moderate evidence to support use of alpha-blockers for larger stones (≥5 mm). Published online Dec. 1 in The BMJ, first author John M. Hollingsworth, MD, said that The Lancet’s results prompted the researchers to study 1,136 subjects in the United Kingdom.

Why the discrepancy with these and other studies? Dr. Nakada thinks that while the therapeutic benefit of MET may be in question, the varying designs of the studies, including different endpoints, might also contribute to the variable nature of the findings.

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Dr. PremingerDr. Preminger said the use of varying endpoints is the primary reason for the diversity of MET study outcomes.

“When they determined whether the treatment was successful or not, the study in The Lancet used intention to treat as their endpoint… as opposed to many other studies that performed imaging studies to specifically document whether or not the ureteral stone was still present. Many argue that The Lancet study was flawed because they never definitively proved whether or not the stone had passed,” Dr. Preminger said.

Next: Which patients are most likely to benefit?

Which patients are most likely to benefit?

Studies have shown that MET seems beneficial in certain stone patients but not in others.

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The most recent meta-analysis by Hollingsworth et al in TheBMJ highlighted when MET is most beneficial, according to Dr. Preminger.

“Besides being more effective to facilitate the passage of distal ureteral calculi, MET appears to be most beneficial in larger stones-5 mm or greater. This finding makes sense because if you have a stone that’s only 3 mm to 4 mm, chances are that stone is going to pass whether [or not] you prescribe MET,” Dr. Preminger said. “I would offer that you should use MET in stones 5 mm or greater, and it’s a toss-up whether you use it for smaller stones.”

Dr. NakadaDr. Nakada said he’s more likely to recommend surgical intervention for stones approaching 1 cm with obstruction and symptoms, rather than wait out MET therapy. He does, however, usually prescribe MET for patients with smaller distal stones and for patients who have a history of passing stones.

Both urologists prescribe tamsulosin because, they say, that’s the drug most used in studies. But all three commonly prescribed alpha-blockers-doxazosin, terazosin, and tamsulosin-have been shown to have similar efficacy in this off-label use, according to Dr. Nakada.

“We prefer tamsulosin. We’ve found that it’s well tolerated in males and females,” Dr. Preminger said. “It’s still our routine that when a patient is seen in the emergency department in our institution, if the patient is able to be sent home and doesn’t need emergent treatment, we will routinely give them tamsulosin, 0.4 mg daily. We’ll see the patient back in 4 to 6 weeks for follow-up imaging, and to make the decision whether or not further surgical intervention is warranted.”

Big-picture benefits, drawbacks

Generic MET doesn’t greatly impact health care costs, either positively or negatively, according to Dr. Nakada.

“The drug is not that expensive, and you would give it really for a short course-studies indicate 2 to 4 weeks,” Dr. Nakada said. “Potentially, if it were successful, this approach would lower health care expenditures because people wouldn’t need surgery.”

Where it might have greater impact is on disease-specific health-related quality of life, according to Dr. Nakada.

“If you can avoid more surgery and pass more stones, that would substantially improve the patients’ health-related quality of life related to stones. We have a large cooperative group studying this using our quality of life instrument,” he said. That study should be out in the next year.

Data already show that MET can reduce pain and time to stone expulsion (by 5 to 7 days) and emergency room visits, according to Dr. Nakada.

“Those are the historical studies and include the use of steroids. Similar findings were not identified by The Lancet study,” he said.

Drawbacks of prescribing MET are minimal.

“The side-effect profile for tamsulosin is good. Generally, less than 10% of people get any significant side effects. Anecdotally, the elderly and some women tend to struggle more with an alpha-blocker than men, with hypotension and nasal stuffiness being the main common side effects,” Dr. Nakada said.

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Dr. Preminger said that in his experience, orthostatic hypotension is more common in older patients and is less common in the age groups normally treated for kidney stones.

Next: The bottom line

The bottom line

Dr. Nakada said that while he doesn’t think The Lancet study was the last word on MET use in kidney stone patients, the findings were powerful.

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“There’s going to be a substantial North American [National Institutes of Health] study, the results of which will come out this spring. That is a direct comparison of tamsulosin to placebo. That could be the last word,” Dr. Nakada said. “That being said, I tend to lean toward The Lancet findings, because, even in my own clinical practice, I’ve not noticed a tremendous change in how patients pass stones despite using tamsulosin routinely for nearly a decade.”

Dr. Preminger said he and colleagues who wrote the AUA guidelines on the topic stand by MET’s worth.

“One of the arguments in The Lancet article was that they would not treat with MET to save their medical resources for something else,” Dr. Preminger said. “My argument would be that if treatment with tamsulosin is safe, relatively effective, and inexpensive, and it can prevent the need for ureteroscopy or shock wave lithotripsy, why not use it? We see very little downside and significant upside to medical expulsive therapy.”

According to Dr. Preminger, the AUA guidelines panel recently launched a new set of guidelines for surgical stone management, which was presented at the 2016 AUA annual meeting in San Diego.

“The guidelines support the use of MET, and I should note that this large meta-analysis that was just reported in The BMJ commented that their meta-analysis supported the guidelines. So, the two are in agreement,” Dr. Preminger said.

There is a better alternative to MET, Dr. Nakada said. That is kidney stone prevention.

“Prevention, in terms of improved diet, improved hydration status, and medical intervention represent the best possible scenario,” Dr. Nakada said. “To prevent stones in the first place is the holy grail.”

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