Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) are set to revolutionize the treatment of hypercholesterolemia in the management of atherosclerotic risk, but numerous reports have detailed unprecedented barriers to access for these drugs. To overcome these challenges, our group created a model to facilitate provision of this new therapy for patients who qualify according to FDA criteria. This report details the real-world follow-up experience of PCSK9i use in a large patient cohort structured to ensure rigor in data collection, analysis, and interpretation. The 271 patients approved and actively followed in our PCSK9i clinic between July 2015 and August 2018 represent a 97% approval rate from insurance, with 28% of prescriptions requiring at least one appeal. Over 50% of patients were statin intolerant. On average, there was a median lapse of 15 days between initial visit and insurance approval. PCSK9i therapy was affordable for most patients, with an average monthly out-of-pocket expense of $58.05 (median $0). Only 2.3% of patients were unable to initiate or continue therapy due to cost. Reductions from baseline in LDL cholesterol and Lp(a) were comparable to published reports with median reductions of 60% and 23% at one year, respectively. PCSK9i therapy was well tolerated overall, though 9% of patients reported adverse events, and 5% of patients discontinued due mostly to musculoskeletal and flu-like symptoms. Our practice model demonstrates that PCSK9i therapy can be accessed easily and affordably for the majority of eligible patients, resulting in dramatic improvement in lipid profile results. Moreover, our registry data suggest that results from the prospective clinical trials of PCSK9i on LDL and Lp(a) reduction and on tolerability are applicable to a real-world cohort.

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Rapid regulation of relaxation is essential to allow the heart to alter stroke volume in response to stress. Inasmuch as Ca2+ transport by the sarcoplasmic reticulum (SR) is an important determinant of relaxation, the purpose of this study was to examine developmental differences in the ability of isoproterenol to alter relaxation time and to determine if these differences were associated with age-related changes in Ca2+ transport by the SR in isolated, perfused adult and newborn guinea pig hearts. Control values of the time constant of isovolumic relaxation (tau) were 37.8 +/- 5.9 ms in adult hearts (n = 8) and 31.6 +/- 5.3 ms in newborn hearts (n = 6). With maximum isoproterenol stimulation, the decrease in tau was significantly greater in adult (51.1 +/- 8.8%, mean +/- SD) compared with that in newborn (26.3 +/- 3.1%, P less than or equal to 0.0001) hearts. Ca2+ uptake, Ca2(+)-dependent adenosinetriphosphatase activity, and Ca2+ pump density were all significantly greater in SR vesicles isolated from adult hearts compared with values measured in SR vesicles from newborn hearts. We conclude that developmental differences in the capacity of the SR to sequester Ca2+ may contribute to age-related differences in the functional response of the heart to isoproterenol.