Naftopidil helps facilitate small ureteral stone passage in men
The alpha-1 blocker naftopidil facilitated spontaneous expulsion of small ureteral stones in men, highlighting its potential in medical expulsive therapy (MET) for individuals with ureteral stones, a Japanese study has shown.
“Conservative [MET] in Japan has commonly involved QS* extract and flopropione with NSAIDs** to reduce ureteral spasms that induce stone stagnation, promote stone expulsion, and alleviate renal colic,” said the researchers. “[While] the pain [may be] controlled within several hours … placement of indwelling ureteral stents may be urgently indicated when severe pain continues,” they added.
“[Our findings suggest that] for relatively small ureteral stones, administration of naftopidil in addition to … NSAIDs for pain relief [and high water intake] might be necessary,” said the researchers. This would eliminate the need for stent placement or minimally invasive management, they said.
A total of 500 men were randomized 1:1:1:1, with those in arm A only given analgesics (controls), those in arm B given daily flopropione 240 mg and QS extract 1,350 mg, those in arm C given naftopidil 50 mg alone, and those in arm D given naftopidil plus flopropione and QS extract. Patients were followed for a month. Stones were classified by location (whole, proximal, medial, or distal ureter [WU, PU, MU, or DU, respectively]) and size (<6 mm [small] or >6 mm [large]). [J Clin Med Res 2019;11:495-500]
Multivariate analysis revealed better stone passage in arm C vs arm A (hazard ratio [HR], 1.43, 95 percent confidence interval [CI], 1.00–2.03; p<0.05 [WU] and HR, 1.56, 95 percent CI, 1.01–2.39; p<0.05 [DU]) and vs arm B (HR, 2.18, 95 percent CI, 1.48–3.23; p<0.0001 [WU], HR, 2.40, 95 percent CI, 1.22–4.73; p=0.01 [PU], and HR, 2.06, 95 percent CI, 1.25–3.41; p=0.005 [DU]).
Expulsion of small stones in the WU and DU was similarly better in arm C vs arm A (HR, 1.57, 95 percent CI, 1.04–2.37; p=0.04 and HR, 1.78, 95 percent CI, 1.06–2.96; p=0.02, respectively) and vs arm B (HR, 2.00, 95 percent CI, 1.27–3.15; p=0.003 and HR, 2.10, 95 percent CI, 1.19–3.72; p=0.01, respectively).
“[These findings suggest that] naftopidil alone facilitated stone expulsion … through the overall range of ureteral stones [and distal and small] ureteral stones,” said the researchers.
The addition of naftopidil to flopropione and QS extract also facilitated stone expulsion regardless of stone size as suggested by the Cox proportional hazards model comparing arm D with arm B (HR, 1.96, 95 percent CI, 1.32–2.91; p=0.0008 [WU] and HR, 2.54, 95 percent CI, 1.30–4.98; p=0.006 [PU]).
However, given the ability of naftopidil alone to successfully facilitate ureteral stone passage, these results imply that flopropione and QS extract have negligible effects on the overall likelihood of stone passage, the researchers pointed out.
Moreover, despite evidence showing the ability of QS extract to dissolve calcium phosphate crystals, [Hifu to Hinyo 1967;30:426-431] the stones in the present study were primarily composed of calcium oxalate or a mixture of calcium oxalate and calcium phosphate, noted the researchers. “Therefore, it is likely that … the QS extract [only targeted] stones containing calcium phosphate … [hence the need to reconsider its] role for promoting stone expulsion.”
None of the large ureteral stones were passed spontaneously, suggesting the limited involvement of naftopidil in the expulsion of relatively large stones, noted the researchers. Additional interventions for symptomatic patients with large stones may thus be necessary, they added.