Pharmacoeconomics of PCSK9 inhibitors in 103 hypercholesterolemic patients referred for diagnosis and treatment to a cholesterol treatment center

BACKGROUND: PCSK9 inhibitor therapy has been approved by the FDA as an adjunct to diet-maximal tolerated cholesterol lowering drug therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) with suboptimal LDL cholesterol (LDLC) lowering despite maximal diet-drug therapy. With an estimated ~24million of US hypercholesterolemic patients potentially eligible for PCSK9 inhibitors, costing ~ $14,300/patient/year, it is important to assess health-care savings arising from PCSK9 inhibitors vs ASCVD cost. METHODS: In 103 patients with HeFH, and/or ASCVD and/or suboptimal LDLC lowering despite maximally tolerated diet-drug therapy, we assessed pharmacoeconomics of PCSK9 inhibitor therapy with lowering of LDLC. For HeFH diagnosis, we applied Simon Broome’s or WHO Dutch Lipid Criteria (score >8). Estimates of direct and indirect costs for ASCVD events were calculated using American Heart Association (AHA), U.S. DHHS, Healthcare Bluebook, and BMC Health Services Research databases. We used the ACC/AHA 10-year ASCVD risk calculator to estimate 10-year ASCVD risk and estimated corresponding direct and indirect costs. Assuming a 50$8,904,361 ($4,328,623 direct,$4,575,738 indirect), the median 10-year risk of a new CVD event was calculated to be 13.1 % with total cost $1,654,758. Assuming a 50$4,452,180 would have been saved in the past; and future 10-year savings would be $1,123,345. CONCLUSION: In the 61 CVD patients, net costs/patient/year were estimated to be$7,000 in the past, with future 10-year intervention net costs/patient/year being $12,459, both below the$50,000/year quality adjusted life-year gained by PCSK9 inhibitor therapy

Thrombophilia in Klinefelter Syndrome With Deep Venous Thrombosis, Pulmonary Embolism, and Mesenteric Artery Thrombosis on Testosterone Therapy: A Pilot Study

We compared thrombophilia and hypofibrinolysis in 6 men with Klinefelter syndrome (KS), without previously known familial thrombophilia, who had sustained deep venous thrombosis (DVT)–pulmonary emboli (PE) or mesenteric artery thrombosis on testosterone replacement therapy (TRT). After the diagnosis of KS, TRT had been started in the 6 men at ages 11, 12, 13, 13, 19, and 48 years. After starting TRT, DVT-PE or mesenteric artery thrombosis was developed in 6 months, 1, 11, 11, 12, and 49 years. Of the 6 men, 4 had high (&gt;150%) factor VIII (177%, 192%, 263%, and 293%), 3 had high (&gt;150%) factor XI (165%, 181%, and 193%), 1 was heterozygous for the factor V Leiden mutation, and 1 was heterozygous for the G20210A prothrombin gene mutation. None of the 6 men had a precipitating event before their DVT-PE. We speculate that the previously known increased rate of DVT-PE and other thrombi in KS reflects an interaction between prothrombotic, long-term TRT with previously undiagnosed familial thrombophilia. Thrombophilia screening in men with KS before starting TRT would identify a cohort at increased risk for subsequent DVT-PE, providing an optimally informed estimate of the risk/benefit ratio of TRT. </jats:p