Regular Users of PDE5Is May Have Increased Risk For Ocular Adverse Events

Mahyar Etminan, PharmD, MSc

New findings suggest regular users of phosphodiesterase type 5 inhibitors (PDE5Is) might have an increased risk for ocular adverse events, including serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION).

For each individual outcome, data show the usage of PDE5Is was independently associated with an increased risk in older men.

“The findings suggest individuals who regularly use PDE5Is need to be cognizant of ocular adverse events associated with these drugs and alert their physicians if they experience any visual deficits,” wrote study author Mahyar Etminan, PharmD, MSc, Collaboration for Epidemiology of Ocular Diseases (CEPOD), Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia.

Previously, small case reports and small epidemiologic studies quantified the risk of ocular adverse events associated with the use of PDE5Is, with conflicting results. However, no epidemiologic data on the risk of SRD and RVO were previously available.

The current, large cohort study quantified the risk for SRD, RVO, and ION associated with the use of PDE5Is using data obtained from the PharMetrics Plus database (IQVIA) from January 2006 - December 2020.

Investigators created a cohort of new users of PDE5Is, including sildenafil, tadalafil, vardenafil, and avanafil, who did not use any of the drugs in the year prior to study entry. They were followed up until the diagnosis of SRD, RVO, or ION, or termination of health coverage.

Additionally, investigators defined cases as a composite of any of the 3 outcomes, examining each separately and randomly identified 4 patients as controls.  They calculated adjusted incidence rate ratios (IRR) with 95% CIs, controlling for hypertension, coronary artery disease, smoking, and diabetes, as well as sleep apnea for the ION outcome.

A total of 213,033 men receiving PDE5Is made up the cohort. The case-control analysis consisted of a total of 1146 cases of SRD (n = 278), RVO (n = 628), and ION (n = 240) and 4584 controls. The mean age for each group was 64.6 years.

Patients with SRD, RVO, and ION were more likely to have hypertension, diabetes, cardiovascular disease, or sleep apnea, compared to control.

Data show the adjusted IRR for the composite end points of any of the 3 outcomes was 1.85 (95% CI, 1.41 - 2.42; incidence, 15.5 cases per 10,000 person-years). The adjusted IRR for SRD as an individual outcome was 2.58 (95% CI, 1.55 - 4.30), with an incidence of 3.8 cases per 10,000 person-years.

Further, the adjusted IRR for RVO was 1.44 (95% CI, 0.98 - 2.12), with an incidence of 8.5 cases per 10,000 person-years and the adjusted IRR for ION was 2.02 (95% CI, 1.14 - 3.58), with an incidence of 3.2 cases per 10,000 person-years.

When the primary analysis was restricted to cases without hypertension, diabetes, or coronary artery disease, data show the IRR remained elevated at 2.12 (95% CI, 1.34 - 3.43).

Additionally, a dose-response analysis comparing risk of those taking ≥5 prescriptions compared to those taking ≤5 prescriptions showed a dose-response association for the overall analysis (IRR, 2.90; 95% CI, 1.15 - 3.81 versus IRR, 1.74; 95% CI, 1.10 - 6.77).

The study, “Risk of Ocular Adverse Events Associated With Use of Phosphodiesterase 5 Inhibitors in Men in the US,” was published in JAMA Ophthalmology.