Use of PCSK9 Inhibitors in Solid Organ Transplantation Recipients.

Standard lipid-lowering therapies in solid organ transplantations pose challenges due to interactions with immunosuppressants. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid-lowering therapies with potential promise in this population. We describe PCSK9i as an efficacious and safe option for management of hypercholesterolemia in solid organ transplantations. (Level of Difficulty: Advanced.).

Application of PCSK9 Inhibitors in Practice.

PCSK9i (protein convertase subtilisin/kexin type 9 inhibitors) 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 Food and Drug Administration 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 because of cost. Reductions from baseline in LDL (low-density lipoprotein) cholesterol and Lp(a) (lipoprotein [a])were comparable to published reports with median reductions of 60% and 23% at 1 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.

Cardiac Rehabilitation for Adults With Congenital Heart Disease: Physical and Psychosocial Considerations.

Owing to significant medical advances, it is now estimated that more than 90% of persons born with congenital heart disease (CHD) will reach adulthood. Medically appropriate physical activity represents an opportunity to improve physical functioning as well as quality of life and psychosocial outcomes. By reviewing published CHD research and clinical recommendations, herein we first summarize how adults with CHD are known to be less physically active and have reduced exercise capacity compared with healthy peers. Cardiopulmonary exercise testing is important for routine clinical management and before the onset of an exercise program. Physiological anomalies are common in adults with CHD, although very few necessitate activity restrictions, and positive results from exercise training have been demonstrated. In recent decades, the focus has thus shifted from restriction of exercise to promotion of exercise. Adults with CHD also face unique psychosocial challenges associated with living with a chronic cardiac condition, many of which may influence exercise behaviours. However, much less is known about participation of adults with CHD in cardiac rehabilitation (CR) programs, which differ from exercise training in their comprehensive, interdisciplinary approach to management of chronic disease and that might be uniquely poised to meet the physical and psychosocial needs of adults with CHD. Initial CR outcomes have been positive and with no reported adverse events. This review summarizes the unique physical and psychosocial considerations that may guide the provision of CR to adults with CHD.

Discordant response of low-density lipoprotein cholesterol and lipoprotein(a) levels to monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9.

BACKGROUND: Clinical trials testing proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated an unanticipated but significant lipoprotein (a) (Lp(a))-lowering effect, on the order of 25% to 30%. Although the 50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C) achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR) preservation, the mechanism for Lp(a) lowering is unknown. OBJECTIVE: We sought to characterize the degree of concordance between LDL-C and Lp(a) lowering because of PCSK9i in a standard of care patient cohort. METHODS: Participants were selected from our Center for Preventive Cardiology, an outpatient referral center in a tertiary academic medical center. Subjects were included in this study if they had (1) at least 1 measurement of LDL-C and Lp(a) before and after initiation of the PCSK9i; (2) baseline Lp(a) > 10 mg/dL; and (3) continued adherence to PCSK9i therapy. They were excluded if (1) they were undergoing LDL apheresis; (2) pre- or post-PCSK9i LDL-C or Lp(a) laboratory values were censored; or (3) subjects discontinued other lipid-modifying therapies. In total, 103 subjects were identified as taking a PCSK9i and 26 met all inclusion and exclusion criteria. Concordant response to therapy was defined as an LDL-C reduction >35% and an Lp(a) reduction >10%. RESULTS: The cohort consisted of 26 subjects (15 females, 11 males, mean age 63 ± 12 years). Baseline mean LDL-C and median Lp(a) levels were 167.4 ± 72 mg/dL and 81 mg/dL (interquartile range 38-136 mg/dL), respectively. The average percent reductions in LDL-C and Lp(a) were 52.8% (47.0-58.6) and 20.2% (12.2-28.1). The correlation between %LDL and %Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 (P < .01). All subjects except for 1 had a protocol-appropriate LDL-C response to therapy. However, only 16 of the 26 (62%; 95% confidence interval 41%-82%) subjects had a protocol-concordant Lp(a) response. Although some subjects demonstrated negligible Lp(a) reduction associated with PCSK9i, there were some whose Lp(a) decreased as much as 60%. CONCLUSIONS: In this standard-of-care setting, we demonstrate moderate correlation but large discordance (∼40%) in these 2 lipid fractions in response to PCSK9i. The results suggest that pathways beyond the LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the potential to significantly lower Lp(a) in select patients, although confirmation in larger multicenter studies is required.

Central vein hardware: cannot live with it, cannot live without it.

Central vein catheters for dialysis have become an integral and unavoidable access modality for providing hemodialysis therapy despite all their major drawbacks. We report a clinical decision dilemma that every nephrologist will encounter while considering an ideal dialysis access for the steadily aging dialysis population.

Retrospective analysis of catheter recirculation in prevalent dialysis patients.

Catheter recirculation (CR) occurs when blood returning from the venous limb of the catheter re-enters the arterial limb of the catheter without passage through the circulation. Adequacy of dialysis is influenced by the degree of access recirculation. In this study we evaluate factors influencing the degree of dialysis central venous catheter (CVC) recirculation in prevalent hemodialysis patients. This is a retrospective study of all patients undergoing hemodialysis via a catheter at the Wake Forest University Outpatient Dialysis Facilities from September 1, 2006 to May 15, 2007. CR was correlated to catheter type, catheter brand, site of placement, catheter length, time on dialysis, time on the current catheter, and was measured via ultrasound dilution technique. A total of 165 catheters were identified. Seventy-one catheters were in the right internal jugular position, 43 in the left internal jugular position, 13 in the right subclavian, one in the left subclavian, eight in the right femoral, two in the left femoral, and four in the trans-lumber position. CR was 6.3 +/- 7.5% in symmetric tip catheters (n = 14), 6.0 +/- 8.3% in split-tip catheters (n = 102), 8.4 +/- 11.7% in step-tip catheters (n = 10), and 23.0 +/- 8.2% in temporary catheters (n = 3), respectively. These results are borderline significant if temporary catheters are included (p = 0.052); however, the overall p-value is only 0.80 for tunneled dialysis catheters. There was no correlation between CR and time on dialysis (p = 0.66) or time on the current catheter (p = 0.48). The current study suggests that the CVC recirculation is independent of catheter brand, type, time on dialysis, or time on current catheter.