Jurgens, Donald James

9513 Background: Hot flashes are a major problem in many women for which better treatment options are needed. Given the known efficacy of gabapentin for decreasing hot flashes, it was decided to evaluate pregabalin, with hopes that it would work better and/or with fewer toxicities. Methods: A three-arm, double-blinded, placebo-controlled randomized trial was developed. Women with bothersome hot flashes (at least 28/week) were randomized to receive either a placebo or target pregabalin oral doses of 75 mg bid or 150 mg bid (starting at 50 mg/d and then increasing the dose at weekly intervals to 50 mg bid, then 75 mg bid, and then, in the higher dose arm, 150 mg bid); patients were treated for 6 weeks. Hot flash numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flash diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intra-patient difference in hot flash score between baseline and week six, comparing the higher dose pregabalin arm and the placebo arm. With the planned sample size of 55 patients per arm, there was an 80% power and two-sided 5% Type I error rate to detect a difference of 0.54 standard deviations, or 1.08 hot flashes per day, or 2.7 units of hot flash score per day. Results: 207 patients were randomized between 6/20/2008 and 8/21/2008. The study arms were well balanced. Mean/median daily hot flash scores and frequencies for all pts at baseline were 15.7/13.4 and 8.3/7.7, respectively. The table shows the decreases in hot flashes from the baseline to the sixth treatment week. Larger numbers illustrate greater hot flash reductions. Toxicity information, quality of life information, and information regarding the effects of hot flashes on subjective symptoms will be available at the meeting time. Conclusions: Pregabalin reduces hot flashes in women. There appears to be similar effects with both studied doses. [Table: see text] No significant financial relationships to disclose.

Abstract 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). Interval (months) Ejection fraction (%) Sex Diagnosis Diagnosis to ICM Anagrelide treatment to ICM Pre-treatment At ICM diagnosis Off-anagrelide therapy for 0.2–16 months F PV 66 60 69 30 and then 18 with continued anagrelide therapy 28 F ET 8 6 N/A 30 N/A F PV 120 36 N/A 20 66 F PV 156 13 73 35 55 F ET 108 10 N/A 35 44 F ET 108 11 58 10 34 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.

Purpose Hot flashes are a common problem for which effective and safe treatments are needed. The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes. Patients and Methods A double-blind, placebo-controlled, randomized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo. Hot flash frequencies and scores (frequency times mean severity) were recorded daily during a baseline week and for six treatment weeks. The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 between the 150 mg twice daily target pregabalin treatment and placebo. Nonparametric Wilcoxon rank sum tests, two-sample t tests, and χ 2 tests were used to compare the primary and secondary hot flash efficacy end points between pregabalin treatments and placebo. Results Hot flash score changes available for 163 patients during the sixth treatment week compared with a baseline week decreased by 50%, 65%, and 71% in the placebo, and target 75 mg twice daily and 150 mg twice daily pregabalin arms, respectively (P = .009 and P = .007, comparing respective pregabalin arms to the placebo arm). While some toxicities were significantly more common in the pregabalin arms, being more evident with the higher dose, pregabalin was generally well tolerated by most patients. Conclusion Pregabalin decreases hot flashes and is reasonably well tolerated. A target dose of 75 mg twice daily is recommended. Its effects appear to be roughly comparable to what has been reported with gabapentin and with some newer antidepressants.