Relapsing and Progressive Complications of Severe Hypertriglyceridemia: Effective Long-Term Treatment with Double Filtration Plasmapheresis.

BACKGROUND: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. OBJECTIVES: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera-py refractory patients. METHODS: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients' incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. RESULTS: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587-28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340-12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa-ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7-2.6) to 0 (IQR 0.0-0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. CONCLUSION: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.

Real-world study: Escalating targeted lipid-lowering treatment with PCSK9-inhibitors and lipoprotein apheresis.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid-lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long-term LA. PATIENTS AND METHODS: In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)-hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. RESULTS: Mean LDL-C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk-adjusted LDL-C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL-C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). CONCLUSION: Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real-world study. The termination of long-term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL-C reduction.

Comparison of two types of synthetic biodegradable barriers for GTR in interproximal infrabony defects: clinical and radiographic 24-month results.

The aim of the present study was to compare the efficacy of guided tissue regeneration (GTR) using two different biodegradable barriers (polylactide acetyltributyl citrate; polydioxanon) in three- and two-walled infrabony defects. The polydioxanon barrier is an experimental GTR membrane that consists of a continuous occlusive barrier with a layer of slings on the side that is meant to face the mucoperiosteal flap. Fifteen patients provided 15 pairs of similar contralateral periodontal defects: 12 predominantly two-walled and 18 predominantly three-walled infrabony defects. Each defect was randomly assigned to treatment with polylactide acetyltributyl citrate (control) or polydioxanon (test) devices. At baseline, 6, 12, 18, and 24 months after surgery, clinical measurements were performed and standardized radiographs obtained (not at 18 months). Both treatments revealed a significant Gingival Index reduction, probing depth reduction, and vertical probing attachment level gain 24 months after surgery. Both treatments showed slight resorption of the crestal alveolar ridge after 24 months, which failed to reach statistical significance. A statistically significant bone gain within the infrabony pockets was measured for both treatment options 24 months postsurgical. Regarding Gingival Index and probing depth reduction as well as vertical probing attachment level and bone gain, there were neither statistically significant nor clinically relevant differences between test and control barriers. The use of both biodegradable barriers in GTR therapy may be recommended.