D28-12 Reveal 2.0 Risk Scores Are Associated With Specific and Early Periods of Clinical Worsening in Pulmonary Arterial Hypertension

Rationale

Patients with pulmonary arterial hypertension (PAH) require close monitoring due to risk of clinical worsening (CW). Risk stratification in PAH is associated with CW, and patients with higher risk scores probably need more frequent follow-up visits to prevent CW; however, optimal follow-up intervals - those which balance clinical need with patient burden - are uncertain and often subjectively determined. Guideline statements recommend follow up intervals of 3-6 months after the first assessment, acknowledging that these intervals should be individualized. We aimed to identify CW timepoints after index visit.

Methods

Using a harmonized patient dataset from major FDA registration trials in PAH, available through the Pulmonary Hypertension Outcome Risks Assessment (PHORA) database, Kaplan-Meier (KM) curves were developed to determine the probability of a no clinical worsening event (PNCW) at 100 days (as defined in parent trials) based on REVEAL 2.0 risk stratification. Kernel-smoothed hazard functions were used to identify the time points at which the instantaneous PNCW risk was highest for each risk strata. At each of these “peak risk” moments, both the hazard rate (the immediate risk at that moment) and the time-varying hazard ratio (how much higher the risk is compared to the typical risk level for each group) are reported.

Results

Data from 3175 patients was included. Patients with REVEAL 2.0 risk scores of 9 or 10 or greater had an initial CW point of 31 and 29 days, with PNCW of 0.995 (95%CI 0.0.97,0.997) and 0.989 (95%CI 0.979,0.999) respectively, whereas patients with risk scores of 6-8 had CW points of 72, 83, and 87 days, respectively. Those with a risk score of 5 or less had a CW point at 94 days (PNCW 0.996, 95%CI 0.993-1). Hazard rate curves demonstrated significant early CW peaks (at ∼30 days) for patients with risk score of 9 or greater, with several regular peaks at approximately 20-30 day intervals thereafter. Significant CW peaks were seen for all patients at days 83-94.

Conclusions

In PAH, patients’ REVEAL 2.0 risk scores are associated with specific timepoints of CW risk within 100 days of the index visit. Patients with high-risk scores are at a substantial risk of clinical worsening at approximately 30 days, whereas lower risk patients’ CW risk appears later, at around 80-90 days. These timepoints may be considered when determining optimal follow-up intervals for PAH patients, based on their initial REVEAL 2.0 risk score.

This abstract is funded by: NIH