Impact of statin use on cardiovascular and hematologic outcomes among patients with myeloproliferative neoplasms

Abstract Introduction: Myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a group of hematopoietic stem cell disorders associated with an increased risk of cardiovascular disease (CVD), including arterial thrombosis and heart failure (HF). Statin use in the general population for primary and secondary prevention has been shown to reduce adverse cardiovascular (CV) events. Additionally, prior epidemiologic studies have showed an association between statin use and decreased risk of incident MPNs. However, the role of statins in preventing major adverse CV events (MACE) and hematologic progression has not been systematically assessed in MPNs and remains unclear. Methods: The analysis of a multicenter retrospective registry of MPN patients with ≥ 1 transthoracic echocardiogram (TTE) after diagnosis of MPN at Massachusetts General Hospital, New York University Langone Health, and University of Chicago from 2010 to 2024 was performed. Patients treated with statins at the time of the first TTE were compared with patients without statin use. CV outcomes were arterial thrombosis, HF hospitalization, and all-cause death. Hematologic progression was defined as progression to secondary MF or acute leukemia. Multivariable logistic regression was performed to estimate propensity score (PS) of statin use and inverse probability treatment weighting (IPTW) was performed to assess association between statin use and outcomes. Competing-risk regression and Cox proportional hazards regression were utilized. Among patients on statins, a subgroup analysis was performed to assess the effect of high-intensity statin use (rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg) compared with low or medium intensity statins. Multivariable competing-risk regression and Cox proportional hazards regressions were utilized to compare high vs. low-intermediate intensity statin. Results: A total of 669 patients (267 PV, 234 ET, 168 MF) were included in the study, of whom 294 (43.9%) were treated with statins, 338 (50.5%) were female, 561 (83.9%) were White race, and 488 (72.9%) had class I indication for statin therapy per cardiology guidelines. The median time of follow-up was 37.7 months (IQR 12.1, 85.3). Patients treated with statins were older (mean 74.5 vs. 68.4 years, p < 0.001), more likely to have class I statin indication (85.0% vs. 63.5%, p < 0.001), less likely to be female (45.6% vs. 54.4%, p = 0.024), and less likely to have MF (18.0% vs. 30.7%, p < 0.001). There was no difference in canonical driver mutation (JAK2, CALR, or MPL) or presence of non-phenotypic driver mutations. Patients treated with statins had higher rates of prior CVD and CV risk factors including HF (18.0% vs. 10.4%, p = 0.004), coronary artery disease (36.7% vs. 12.3%, p < 0.001), and diabetes (20.7% vs. 9.3%, p < 0.001). After IPTW, co-morbidities and patient characteristics were well-balanced. After IPTW, statin use was associated with lower risk of arterial thrombosis (14.4% vs. 20.9%; SHR 0.70, 95% CI 0.54 – 0.92) and HF hospitalization (18.1% vs. 23.9% SHR 0.77, 95% CI 0.61 – 0.98) but not hematologic progression (13.0% vs. 14.1%; SHR 0.96, 95% CI 0.72 – 1.29) or death (37.6% vs. 41.5%; HR 1.04, 95% CI 0.87 – 1.24). Among patients with statin use, there was no difference in arterial thrombosis (SHR 1.07, 95% CI 0.56 – 2.00), HF hospitalization (SHR 0.89, 95% CI 0.50 – 1.57), hematologic progression (SHR 0.91, 95% CI 0.43 – 1.95) or death (HR 0.83, 95% CI 0.51 – 1.35) in high-intensity statin treated patients compared with low- or intermediate intensity statin use. Conclusions: In patients with MPNs, statin use was associated with a reduced risk of arterial thrombosis and heart failure hospitalization, but not with hematologic progression or all-cause mortality. Notably, the intensity of statin therapy did not correlate with clinical outcomes among statin-treated patients. These findings suggest that statins may provide meaningful cardiovascular protection in individuals with MPN, yet appear to be underutilized even among those with established clinical indications. Further prospective studies are warranted to better define the role of statins and optimize cardiovascular risk management in this population.