Anagrelide-Associated Cardiomyopathy in Polycythemia Vera and Essential Thrombocythemia.

Introduction: Anecdotal reports of “idiopathic” cardiomyopathy (ICM) in patients receiving anagrelide therapy have surfaced but not formally studied. We undertook a tertiary-center comprehensive study of ICM that was diagnosed in the setting of either polycythemia vera (PV) or essential thrombocythemia (ET).

Methods: Standard criteria were used for the diagnosis of both ET and PV. A diagnosis of ICM required echocardiogram documentation of a reduced left ventricular systolic ejection fraction (EF < 50%) as well as the absence of both coronary artery disease and other causes of cardiomyopathy. In order to avoid specific drug selection bias, we queried the entire Mayo Clinic Rochester database first for the diagnosis of ‘polycythemia’, ‘thrombocytosis’, or ‘thrombocythemia’ and subsequently cross-referenced the results with the diagnosis of either ‘cardiomyopathy’ or ‘heart failure’.

Results: Initial data inquiry yielded a total of 434 patients whose medical histories were thoroughly reviewed for the presence of an echocardiogram-documented ICM that post-dated a diagnosis of either ET or PV. Nine such patients (7 females; age range 46–78 years) were identified. Anagrelide therapy, at standard doses (median 2 mg/day), was temporally associated with ICM in 4 of the 9 patients while treatment in the remaining 5 patients consisted of either phlebotomy alone (3 patients) or other cytoreductive agents (2 patients). A similar database inquiry at Mayo Clinic Jacksonville identified 2 more patients with ICM that was temporally associated with anagrelide treatment. A normal echocardiogram was documented in 3 of the 6 patients with anagrelide-associated ICM at 2, 15, and 39 months prior to treatment (table 1).

Anagrelide therapy was immediately discontinued when ICM was diagnosed in 5 of the 6 patients and after further worsening of EF on continued anagrelide therapy in the sixth patient (first patient in table 1). All 6 patients with anagrelide-associated ICM experienced symptomatic improvement after drug discontinuation but the corresponding improvement in EF, after a period of 0.2–16 months, was often suboptimal (table 1). In contrast, ICM not associated with anagrelide therapy remained unchanged both in terms of symptoms and EF in all 5 cases.

Conclusion: Anagrelide-induced cardiomyopathy might occur in some patients with either PV or ET. Prompt recognition and drug discontinuation has the potential to adequately reverse the situation in some but not all patients.