Potential Link Found Between Thrombotic Events, Mortality in Patients With PV, ET

Patients with polycythemia vera (PV) or essential thrombocythemia (ET) have a greater thrombotic risk vs the general population, and a recent study published in Leukemia Research found that among patients with PV or ET who had thrombotic events (TEs), mortality risk was higher and survival was shorter compared with those who did not have TEs in the study period.

PV and ET are characterized by the overproduction of erythrocytes and platelets, respectively, and both are rare. Symptoms can include fatigue, night sweats, concentration issues, bone pain, and various clinical features that can make it difficult to accurately diagnose. Shorter overall survival and increased TE risk compared with the general population also affect patients with PV or ET.

Based on Surveillance, Epidemiology, and End Results (SEER) registry data, estimated median overall survival is 12 years and 5-year mortality is 19% for both conditions. High rates of arterial and venous TEs are a known cause of morbidity and mortality in these patients, although study authors note that few contemporary studies have assessed the effect that TEs have on mortality in patients with PV and ET.

The current study aimed to assess mortality risk in patients with high-risk PV and intermediate- to high-risk ET who experienced a TE vs those who did not experience a TE during the study period.

This retrospective, observational study included 50,405 Medicare fee-for-service (FFS) beneficiaries with PV and 124,569 with ET. All data were based on the Medicare FFS claims database, and eligible patients had either a PV or ET diagnosis and at least 1 inpatient or at least 2 outpatient claims between January 1, 2010, and December 31, 2017.

The median patient age was 73 years in the PV group and 76 in the ET cohort. A total of 6268 patients (12.4%) in the PV cohort had a history of TEs before PV diagnosis. Median follow-ups were 34.5 months for the PV cohort and 25.5 months in the ET cohort.

In the ET cohort, 23,908 patients (19.2%) had a history of TEs pre diagnosis. During follow-up, 6023 (12.0%) patients with PV and 14,156 (11.4%) with ET received hydroxyurea. In the PV cohort, 14,571 patients with PV (28.9%) underwent at least 1 phlebotomy.

Although past studies have shown that TEs are common among those with PV or ET, this study showed a particularly high occurrence of TEs despite shorter follow-up times vs previous analyses.

“Notably, most of these prior analyses included substantial proportions of low-risk patients,” the study authors wrote. “Patients included in the current analyses were generally older than previous cohort studies and had high rates of comorbidities, likely due to the age thresholds applied for eligibility for the analysis (≥ 65 years), which may have contributed to increased frequency of vascular complications.”

Of the patients with PV, 14,334 (28.4%) experienced a TE in the follow-up period, with the most common being ischemic stroke (46.0%), transient ischemic attack (TIA; 30.7%), and acute myocardial infarction (AMI; 29.9%). In the ET group, 30,478 patients (24.5%) experienced a postdiagnosis TE. Ischemic stroke (42.5%), AMI (25.9%), and TIA (24.8%) were the most common TEs in this cohort.

After adjusting for other patient characteristics, those in the PV group who experienced a postdiagnosis TE were at an increased risk of mortality than those who did not (adjusted HR [aHR], 18.6; 95% CI, 16.1-21.6; P < 0.001). Patients who experienced pre-index TEs were at an even higher risk (aHR, 34.4; 95% CI, 24.0-49.4; P < 0.001).

In the ET cohort, patients who experienced a TE post diagnosis were also at an increased risk compared with those who did not (aHR, 25.2; 95% CI, 23.1-27.5; P < 0.001). Similar to findings in the PV cohort, patients with ET who had a prediagnosis TE were at a greater risk of mortality than those who did not have a prediagnosis TE (aHR, 37.5; 95% CI, 31.7-44.3).

In both cohorts, hyperlipidemia was a common comorbidity and the authors noted it might also be associated with TE prevalence. Despite the study’s limitations, including reliance on claims data and the lack of treatment data analysis for the overall cohort, the findings suggest that mortality risk was significantly higher in patients who experienced TEs in tandem with PV or ET, they added.

“Thrombosis risk mitigation remains an important management goal in patients with PV and ET, particularly among those with a history of thrombotic events,” the authors wrote, adding, “More studies are needed to better define and understand ET and PV thrombotic event rates in various high-risk populations in a real-world setting.”

Reference

Pemmaraju N, Gerds AT, Yu J, et al. Thrombotic events and mortality risk in patients with newly diagnosed polycythemia vera or essential thrombocythemia. Leuk Res. Published online February 16, 2022. doi:10.1016/j.leukres.2022.106809