Real-World Effectiveness of Preventive Pharmacological Therapy in Patients With Urolithiasis: A Retrospective Cohort Study

Rationale & Objective Data supporting the efficacy of preventive pharmacological therapy (PPT) to reduce urolithiasis recurrence are based on clinical trials with composite outcomes that incorporate imaging findings and which have uncertain clinical significance. This study sought to evaluate if the use of PPT leads to fewer symptomatic stone events. Study Design Retrospective cohort study. Setting & Participants: Medicare enrollees with urolithiasis who completed 24-hour urine collections that revealed hypercalciuria, hypocitraturia, low urine pH, or hyperuricosuria. Exposure PPT (thiazide diuretics for hypercalciuria, alkali for hypocitraturia or low urine pH, or uric acid lowering drugs for hyperuricosuria) categorized as, 1) adherent to guideline-concordant PPT, 2) nonadherent to guideline-concordant PPT, or 3) untreated. Outcome Symptomatic stone event occurrence (emergency department [ED] visit or hospitalization for urolithiasis or stone-directed surgery). Analytical Approach Cox proportional hazards regression. Results Among 13,942 patients, 31.0% were prescribed PPT. Compared to no treatment, concordant/adherent PPT use was associated with a significantly lower hazard of symptomatic stone events for patients with hypercalciuria (hazard ratio [HR], 0.736 [95% confidence interval (CI), 0.593 to 0.915]) and low urine pH (HR, 0.804 [CI, 0.650 to 0.996]) but not for patients with hypocitraturia or hyperuricosuria. These associations were largely driven by significantly lower rates of ED visits after initiating PPT among the concordant/adherent group versus untreated patients. Patients with hypercalciuria had adjusted two-year predicted probabilities of a visit of 3.8% [95% CI, 2.5% to 5.2%%] and 6.9% [95% CI, 6.0% to 7.7%] for the concordant/adherent PPT and no-treatment groups, respectively. Among patients with low urine pH, these probabilities were 4.3% [95% CI, 2.9% to 5.7%] and 7.3% [95% CI, 6.5% to 8.0%] for the concordant/adherent PPT and no-treatment groups, respectively. Limitations Potential bias from the possibility that patients prescribed PPT had more severe disease than untreated patients. Conclusion Patients with urolithiasis and hypercalciuria who were adherent to treatment with thiazide diuretics as well as those with low urine pH adherent to prescribed alkali therapy had fewer symptomatic stone events than untreated patients.