Uso de inhibidores de PDE5 vinculado a un aumento del riesgo de glaucoma

Men who used the PDE5 inhibitor tadalafil (Cialis) for lower urinary tract symptoms (LUTS) had an increased likelihood of developing glaucoma-related clinical events, according to a large retrospective study.

Rates of glaucoma, ocular hypertension, and open-angle glaucoma were significantly higher in men with a history of tadalafil prescriptions for LUTS. These patients were also significantly more likely to initiate treatment for glaucoma as compared with men who did not use a PDE5 inhibitor.

The findings do not prove that PDE5 inhibition can cause glaucoma but add to existing evidence linking the drug class to ophthalmic conditions, reported Chien-Chih Chou, MD, PhD, of Taichung Veterans General Hospital in Taiwan, and colleagues in the British Journal of Ophthalmology.

Importancia de la evaluación oftalmológica

These findings do not contraindicate tadalafil use but highlight the importance of baseline ophthalmic assessment and regular follow-up, particularly in patients with pre-existing glaucoma, ocular hypertension, a family history of glaucoma, high myopia, or those requiring long-term therapy, the authors concluded.

Opiniones de especialistas

According to Stephen Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, the «interesting hypothesis-generating analysis» has a number of limitations that should be kept in mind when considering the findings.

We know tadalafil is used not just for LUTS, but also for ED [erectile dysfunction]. Thus, whether it is the medicine itself or the fact that these men were deemed to need tadalafil is unknown.

For example, systemic hypertension is a risk factor for both ED and glaucoma. While the investigators adjusted for hypertension, they did not adjust for severity of hypertension. Thus, perhaps patients with more severe hypertension also had ED, and this severe hypertension drove the excess glaucoma risk.

Also, the absolute effect — if real — was small. A less than 0.8% increased risk over 5 years. To suggest all men with LUTS starting tadalafil need ophthalmic examination and routine follow-up for a 0.8% increased risk is a huge burden on our health system.

In short, there are many reasons to be cautious in interpreting these results, but they do raise some interesting hypotheses that should be prospectively tested in future clinical studies.

Conflictos en la investigación

The findings also conflict with a study reported at the recent Association for Research in Vision and Ophthalmology meeting. Using the same clinical database as the Taiwanese group, investigators at the University of Miami showed a protective effect against glaucoma in men prescribed PDE5 inhibitors for ED.

Efectos fisiológicos de los inhibidores de PDE5

Inhibition of PDE5 increases intracellular levels of cyclic guanosine monophosphate, leading to smooth-muscle relaxation and vasodilation within target tissues. The physiologic effects have been linked to several systemic adverse effects, including headache, flushing, sensorineural hearing loss, and orthostatic hypotension, Chou and colleagues noted in their background information.

Ocular adverse effects also have been reported among users of PDE5 inhibitors, including rare but serious events such as retinal detachment, retinal vascular occlusion, and ischemic optic neuropathy. However, the association between PDE5 inhibition and glaucoma remains controversial. Moreover, the likelihood of ocular events appears to correlate with treatment intensity.

Investigación adicional necesaria

In theory, PDE5 inhibitor-induced vasodilation may cause transient elevation of intraocular pressure (IOP), but clinical studies have not consistently demonstrated IOP elevation with chronic use. In addition, some studies have suggested that PDE5 inhibition may enhance choroidal and retrobulbar blood flow, which could be protective or have a neutral effect on the long-term clinical course of glaucoma.

To add evidence related to tadalafil use for LUTS and glaucoma risk, Chou and colleagues analyzed data from the TriNetX Analytics Network. They identified men who initiated LUTS treatment with tadalafil during January 2012 to December 2022 and a comparator group of men who did not use a PDE5 inhibitor during the same time period. After propensity matching, the investigators analyzed data for two 36,927-patient cohorts.

Analyses showed small but statistically significant differences in rates of ocular hypertension among men treated with tadalafil (174 vs 137 events, HR 1.32, 95% CI 1.06-1.65), in addition to rates of open-angle glaucoma (166 vs 130 events, HR 1.33, 95% CI 1.05-1.67). Tadalafil users were also significantly more likely to initiate treatment for glaucoma (797 vs 624 events, HR 1.33, 95% CI 1.20-1.47).

A 5-year Kaplan-Meier survival analysis showed that tadalafil users had a greater cumulative probability of glaucoma (3.93% vs 3.16%, P<0.001), ocular hypertension (0.61% vs 0.47%, P=0.014), and glaucoma treatment (2.76% vs 2.05%, P<0.001). The cumulative probability for normal-tension glaucoma and primary angle-closure glaucoma did not differ significantly between tadalafil users and non-users.

Stratification by age and race showed that tadalafil users over 50 and white men had a significantly increased risk of glaucoma (HR 1.29, 95% CI 1.18-1.41, and HR 1.16, 95% CI 1.04-1.29). Stratification by comorbidities showed a consistent pattern of increased glaucoma risk associated with tadalafil use in men with hypertension, hyperlipidemia, type 2 diabetes, obesity, and chronic kidney disease.

Disclaimer: Esta información no sustituye el consejo médico. Siempre consulte con un profesional de salud antes de tomar decisiones sobre su tratamiento o salud.

Fuente: https://www.medpagetoday.com/ophthalmology/generalophthalmology/122498