Certain US Veterans More Likely to be Inappropriately Prescribed PDE5 Inhibitors

U.S. veterans with pulmonary hypertension (PH) due to left heart disease and chronic lung disease are more likely to be inappropriately prescribed phosphodiesterase-5 inhibitors (PDE5i) if they have received care both in and out of the Veterans Health Administration (VA), a study has found.

Other factors for PDE5i treatment, despite guidelines against its use in people with group 2 or 3 PH, include more severe disease and treatment at facilities with higher volumes of PH patients.

The study, “Factors Associated With Potentially Inappropriate Phosphodiesterase-5 Inhibitor Use for Pulmonary Hypertension in the United States, 2006 to 2015,” was published in Circulation: Cardiovascular Quality and Outcomes.

PDE5i are a group of pulmonary vasodilators, including Revatio (sildenafil) and Adcirca (tadalafil), that work by widening blood vessels in the lungs, thus lowering the pressure in these vessels.

PDE5i have been shown effective for pulmonary arterial hypertension (group 1), but studies have deemed them ineffective for patients with group 2 PH, which is caused by heart disease, or group 3 PH, which is caused by lung disease. Rather, evidence suggests that such medications could increase the risk of problems such as kidney disease and heart failure in these individuals.

Due to the lack of benefit and potential risks, guidelines recommend against PDE5i use for treating PH patients in group 2 or 3. Nonetheless, these medications are sometimes prescribed to individuals with these conditions.

In the new study, researchers set out to examine which factors are associated with an increased risk of inappropriate PDE5i prescriptions among U.S. veterans. They were particularly interested in whether veterans who received care from both community providers and the VA might be more likely to get such prescriptions.

“Our primary hypothesis was that veterans with group 2/3 PH initiated on PDE5i treatment via Medicare would be at increased risk for subsequently receiving potentially inappropriate prescriptions in VA,” they wrote.

To test this, the researchers examined data from 34,775 Medicare-eligible veterans with group 2 or 3 PH, who were identified from relevant national databases. The study group was 97.4% male and 79.4% non-Hispanic white; the average age was 74 years.

Of these, 1,556 (4.5%) had received VA prescriptions for PDE5i. The researchers constructed statistical models to identify factors associated with a higher likelihood of being prescribed these medications.

Supporting the researchers’ primary hypothesis, the strongest predictor of PDE5i prescriptions from the VA — a 6.5 times greater likelihood — was prior treatment elsewhere.

Individuals with more severe disease were also more likely to be prescribed PDE5i, as well as those with recent episodes of right heart failure (3.3 times more likely), and those with recent acute respiratory failure (3.7 times more likely).

Previous treatment with other pulmonary vasodilators was associated with a 3.3 times higher likelihood of PDE5i prescription, and previous right heart catheterization also increased the likelihood of such a prescription by 3.8 times.

PDE5i use was also more common in younger patients. Compared with patients 65–74, those younger than 55 were 50% more likely — and those older than 85 were half as likely — to be prescribed PDE5i.

The proportion of patients prescribed PDE5i varied from 0% to 35% at different VA facilities. VA facilities in the Northeast and Southeast were less likely than other regions to prescribe PDE5i, and facilities that saw a lower volume of patients with PH were less likely to prescribe PDE5i.

“Our findings may inform the design of multilevel interventions to deimplement guideline-discordant prescribing of PDE5i for group 2/3 PH, preventing patient harm and waste of resources,” the researchers wrote.

They stressed the importance of openly sharing data across different healthcare systems, and the need for increased education at all levels to reduce the amount of inappropriate prescriptions. In particular, they highlighted the importance of including pharmacists — who may be more familiar with medication particulars than clinicians — in making prescription decisions.

“Our study identifies previously unknown influences on potentially inappropriate PDE5i prescribing for PH and suggests concrete solutions to address them,” the researchers concluded.