Phosphodiesterase type-5 (PDE5) inhibitors are approved by the US FDA for the treatment of pulmonary arterial hypertension. This class of medications is sometimes prescribed for patients with pulmonary hypertension of other etiologies despite lack of data to support efficacy. The off-label practice is potentially dangerous and also costly. Kim and colleagues recently examined data in the Veteran’s Affairs (VA) system to better understand national clinical practice patterns with respect to PDE5 inhibitor use for pulmonary hypertension.
This retrospective analysis used pharmacy prescription data from 2005-2012. The investigators restricted the cohort to subjects with outpatient prescriptions for daily use (to exclude subjects prescribed PDE5 inhibitors for erectile dysfunction). Pulmonary hypertension and its underlying etiology was defined on the basis of an International Classification of Diseases code-based algorithm and validated by chart review of a random sample.
In total, 108 777 subjects with pulmonary hypertension were identified of whom 2,790 (2.6%) received a daily prescription for a PDE5 inhibitor. Based on the algorithm-defined etiology of pulmonary hypertension, only 19% received a prescription consistent with clinical guidelines. Appropriateness could not be determined in an additional 13% of subjects due to incomplete data.
Based on the algorithm-defined etiology of pulmonary hypertension, only 19% received a prescription consistent with clinical guidelines.
Patients inappropriately prescribed PDE5 inhibitors were more likely to be older white men with cardiac disease and hypoxemic lung disease. The use of PDE5 inhibitors contrary to guidelines increased over time, from 53 prescriptions in 2005 to 748 in 2012. The investigators also performed manual chart abstraction to determine the proportion of subjects who were referred for right heart catheterization, the gold standard diagnostic test for pulmonary hypertension. Only 110/230 (48%) patient records reviewed had a documented right heart catheterization and 74/230 (32%) had an echocardiogram with evidence of pulmonary hypertension.
This study is important because it brings to light potential widespread use of PDE5 inhibitors contrary to guideline recommendations. Trials of PDE5 inhibitors in patients with pulmonary hypertension due to left heart disease (WHO Group II) have failed to show benefit. An on-going trial is investigating the use of tadalafil in subjects with pulmonary hypertension and hypoxemic lung disease (WHO Group III). Clinical practice guidelines for pulmonary hypertension do permit a trial of PDE5 inhibition in patients with WHO Groups II and III, but most subjects identified for this study were on therapy long-term.
Clinical inertia may play a role in the surprising numbers receiving the drugs outside of guidelines recommendations as nearly 40% of the prescriptions from the VA were prescribed by an outside provider but were continued by a VA provider. Unfortunately, the methods used for this study did not allow investigation of the underlying rationale for prescribing PDE5 inhibition in a given patient. The use of electronic health record and administrative data is an important approach for identifying epidemiologic trends. However, the inability to extract hemodynamic and echocardiographic data in this study increases the risk of patient misclassification, as evident by a positive predictive value for pulmonary arterial hypertension of only 42%. Despite this limitation, the findings are compelling and raise awareness of the misuse of PDE5 inhibition among patients with pulmonary hypertension in the VA system.
Source: Kim D, Lee KM, Freiman MR, et al. Phosphodiesterase-5 inhibitor therapy for pulmonary hypertension in the United States. Actual versus recommended use. Ann Am Thorac Soc. 2018;15:693–701.