Treatment Of Mixed Hyperlipidemia Research Articles

Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders

Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge. Pancreatic triglyceride lipase (PTL) and Niemann–Pick C1-like 1 (NPC1L1) have been identified as crucial proteins in the transport of triglycerides and cholesterol. Here, cinaciguat, a known agent used in the treatment of acute decompensated heart failure, was identified as a potent dual inhibitor targeting PTL and NPC1L1. We presented in vitro evidence from surface plasmon resonance analysis that cinaciguat interacted with PTL and NPC1L1. Furthermore, cinaciguat exhibited potent PTL-inhibition activity. Fluorescence-labeled cholesterol uptake analysis and confocal imaging showed that cinaciguat effectively inhibited cholesterol uptake. In vivo evaluation showed that cinaciguat significantly reduced the plasma levels of triglycerides and cholesterol, and effectively alleviated high-fat diet–induced intestinal microbiota dysbiosis and metabolic disorders. These results collectively suggest that cinaciguat has the potential to be further developed for the therapy of mixed hyperlipidemia.

Colesevelam

Colesevelam hydrochloride (Cholestagel, WelChol is an orally administered, non-absorbable, polymeric, bile-acid-binding agent with a higher affinity for glycocholic acid in vitro and greater capacity for binding bile acids in vivo than other bile-acid-binding agents. In randomized controlled trials in patients with primary hypercholesterolemia, colesevelam monotherapy reduced mean serum low-density lipoprotein-cholesterol (LDL-C) levels by 9-19%. In combination with an HMG-CoA reductase inhibitor (statin) or fenofibrate, colesevelam induced additive reductions in LDL-C 10-16% greater than those achieved by monotherapy with a statin (in patients with primary hypercholesterolemia) or fenofibrate (in patients with mixed hyperlipidemia). Colesevelam was generally well tolerated, with a relatively low incidence of gastrointestinal adverse events and a high compliance rate. Thus, colesevelam provides a useful addition to primary therapy with statins in the treatment of primary hypercholesterolemia, or fenofibrate in the treatment of mixed hyperlipidemia.

Comparison of the efficacy and safety of atorvastatin and fenofibrate in the treatment of mixed hyperlipidemia

Comparison of the efficacy and safety of atorvastatin and fenofibrate in the treatment of mixed hyperlipidemia

Treatment of mixed hyperlipidemia in coronary artery disease patients with fluvastatin and bezafibrate in monotherapy and combination

Treatment of mixed hyperlipidemia in coronary artery disease patients with fluvastatin and bezafibrate in monotherapy and combination

Comparison of the efficacy of atorvastatin and micronised fenofibrate in the treatment of mixed hyperlipidemia

Comparison of the efficacy of atorvastatin and micronised fenofibrate in the treatment of mixed hyperlipidemia

Comparison of the Efficacy of Atorvastatin and Micronized Fenofibrate in the Treatment of Mixed Hyperlipidemia

To evaluate and compare the influences of micronized fenofibrate and atorvastatin on serum lipid profile, including lipoprotein(a) levels, and on fibrinogen levels in a large group of patients with primary mixed hyperlipidemia (serum total and low-density lipoprotein cholesterol levels > 240 and 160 mg/dl, respectively, and serum triglyceride level > 200 mg/dl). This was a 16-week, open-label, parallel-design study conducted in our lipid clinic. After a 6-week dietary baseline phase, we implemented a treatment phase, during which patients received 10 mg/day atorvastatin (n = 45) or 200 mg/day micronized fenofibrate (n = 46) for 16 weeks. Patients were assigned to one of the drugs in sequential orders. Serum lipid profiles, including levels of lipoprotein(a) and fibrinogen, as well as muscle and liver enzymes, were measured during screening, and during weeks -4, -2, 0, 8, and 16 of the treatment period. Atorvastatin was more effective than was micronized fenofibrate at lowering levels of total and low-density lipoprotein cholesterol, whereas fenofibrate was more effective at lowering levels of triglycerides, and raising levels of high-density lipoprotein cholesterol and apolipoprotein A1. However, micronized fenofibrate could significantly decrease plasma fibrinogen levels, whereas atorvastatin evoked a small increase. Both atorvastatin in small doses and micronized fenofibrate are effective for improving serum lipid profiles of patients with mixed hyperlipidemia. However, there are considerable differences between the two drugs concerning their influences on plasma fibrinogen levels.

Cerivastatin in the treatment of mixed hyperlipidemia: the right study

The ceRIvastatin Gemfibrozil Hyperlipidemia Treatment (RIGHT) study—a multicenter, randomized, double-blind, placebo-controlled study—compared the lipid-lowering effects of cerivastatin, once daily at doses of 0.1, 0.2, and 0.3 mg with those of twice-daily gemfibrozil 600 mg in 751 patients with primary mixed hyperlipidemia. Randomization to the first 16 weeks of treatment followed an initial 4-week washout period and subsequent 6-week diet-controlled, placebo run-in phase. Patients continued to receive study medication for a further 36 weeks, with those previously on placebo switched to 0.1 mg/day cerivastatin at the end of week 16. Additional cholestyramine therapy was permitted at week 36 in patients with uncontrolled low-density lipoprotein (LDL) cholesterol levels. Cerivastatin achieved significant dose-dependent reductions in LDL cholesterol of 15–24% after 16 weeks of treatment, compared with reductions of 7.5% with gemfibrozil. Over this period both cerivastatin (0.3 mg) and gemfibrozil (1,200 mg) significantly decreased levels of triglycerides (20.3% vs 50.3%, respectively) and very low-density lipoprotein (VLDL) cholesterol (30.8% vs 47.1%, respectively), as well as increasing high-density lipoprotein (HDL) cholesterol (11.3% vs 13.3%, respectively). The reductions in LDL cholesterol and other atherogenic lipids and lipoproteins at 16 weeks were sustained in the subsequent 36-week double-blind continuation phase, during which time <10% of patients received additional cholestyramine therapy. Both study drugs were well tolerated, with the incidence of adverse events similar to that of placebo treatment. Clinically significant increases in hepatic transaminases and creatine phosphokinase occurred at a similar low frequency of around 1%. This study demonstrated that cerivastatin is a safe, well-tolerated, and effective treatment for lowering elevated LDL cholesterol and triglycerides in patients with mixed hyperlipidemia.