Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia

Knapp, Howard H; Schrott, Helmut G.; Madelenat, P.; Knopp, Robert H.; Chin, Byong Han; Gaziano, J. Michael; Donovan, Joanne M.; Burke, Steven K.; Davidson, Michael

doi:10.1016/s0002-9343(01)00638-6

Cited by 187 publications

(143 citation statements)

References 27 publications

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“…10,12,13 However, limited information has been available in evaluating a potentially effective first 2-week therapeutic approach for the treatment of patients with hypercholesterolemia using 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor; this issue may be important for patients with acute coronary syndrome. The time course of changes in lipid and lipoprotein levels in the first 2 weeks of therapy with HMG-CoA reductase inhibitor in healthy subjects as well as patients, 6,7 and the rapid reduction in CRP with an 8-week cerivastatin treatment in patients with primary hypercholesterolemia have been demonstrated recently; 11 however, limited data are available in patients with hypercholesterolemia following a 2-week statin therapy. In addition, it is uncertain whether the rapid effect of simvastatin on lipid profile as well as on CRP is generally applicable to other statin agents.…”

Section: Introductionmentioning

confidence: 97%

Rapid effects of simvastatin on lipid profile and C‐reactive protein in patients with hypercholesterolemia

Chen

et al. 2003

Clinical Cardiology

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SummaryBackground: Rapid lowering of low-density lipoprotein (LDL) cholesterol levels as well as C-reactive protein (CRP) by administration of drugs may produce early benefit to the coronary endothelium in patients with coronary heart disease and reduce angina and coronary events after revascularization. Limited information has been available in evaluating a potentially effective first 2-week therapeutic approach for the treatment of patients with hypercholesterolemia using a statin.Hypothesis: The study was undertaken to investigate whether a rapid LDL cholesterol and CRP reduction can be achieved by 2-week simvastatin therapy using a common lipid-lowering protocol in patients with hypercholesterolemia.Methods: Forty-two patients were randomly assigned to 20 or 40 mg/day of simvastatin. Blood samples were drawn at Day 0 and at Day 14 for measuring lipid profile, CRP levels, and hepatic enzymes in all patients.Results: The results showed that both doses of simvastatin (20 and 40 mg) induced significant reductions in total cholesterol (TC, 25 and 38%) and LDL cholesterol (31 and 46%)

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Section: Introductionmentioning

confidence: 97%

Rapid effects of simvastatin on lipid profile and C‐reactive protein in patients with hypercholesterolemia

Chen

et al. 2003

Clinical Cardiology

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“…41 Both combinations of colesevelam with simvastatin reduced mean serum LDL-c by 42% from baseline. Colesevelam 3.8 g + simvastatin 10 mg reduced LDL-c by an additional 16% compared to simvastatin 10 mg monotherapy.…”

Section: Combination With Statinsmentioning

confidence: 97%

“…[40][41][42] No significant interaction has been shown during colesevelam and fenofibrate co-administration or after a 4-hour dosing interval. 43 Although studies have not evaluated any interaction between colesevelam and ezetimibe, significant further reduction in LDL-c levels occurs with combined colesevelamezetimibe therapy.…”

Section: Drug-drug Interactionmentioning

confidence: 98%

Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

2010

Clinical Medicine Reviews in Vascular Health

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Background: Statins are recommended as first line therapy for the prevention of cardiovascular disease. Some individuals are statin intolerant or may need additional cholesterol lowering to achieve their cholesterol targets. Purpose: To review the pharmacology, clinical efficacy and safety of colesevelam mono-and combination therapy in patients with hypercholesterolemia. Data source: English-language journals from PUBMED MEDLINE (without restriction of date) using key word colesevelam. Results: Trials of colesevelam as monotherpy or in combination had baseline LDL-c levels of 130 to 202 mg/dl and triglycerides levels of 114 to 230 mg/dl. Colesevelam monotherapy reduced LDL-c by 9%-20% while increasing triglycerides 6%-25%. When added to low or moderate dose statin therapy, colesevelam decreased LDL-c an additional 6%-16%; when added to fenofibrate, colesevelam additionally decreased LDL-c by 17% and non-HDL-c by 7%; and when added to statin + niacin 2 gr additionally decreased LDL-c by 10%. The hypertriglyceridemia observed with colesevelam monotherapy was largely attenuated when colesevelam was coadministered with statins, fenofibrate, or niacin 2 gr. Coadministration of colesevelam with ezetimibe provided variable additional LDL-c reductions ranging from 0 to 20% over ezetimibe alone, and triglyceride responses were similarly variable. In diabetic individuals with modest hypertriglyceridemia, colesevelam reduced hemoglobin A1c by 0.5%. Colesevelam has fewer drug interactions than older bile acid sequestrants and is well-tolerated when used in combination with other lipid-lowering medications as well as with oral anti-diabetes medications or insulin. Conclusion: Colesevelam is an option for patients who have not achieved their LDL-c and non-HDL-c goals with statin therapy, or who are statin intolerant. Colesevelam is also an option to lower both LDL-c and glucose levels in patients with inadequately controlled diabetes.

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“…First, the relatively small scale of our research may lead to certain underestimation or loss of data associations, which may rewrite the multiple regression analysis and subsequent interpretation. Second, the research duration was not long enough to observe mid or long-term results, although longer lasting investigations unveiling parallel outcomes have demonstrated that the maximal lipid-lowering effect of statins and ezetimibe appears within 2 weeks (26)(27)(28). Third, rosuvastatin we chose in this study could not represent other kinds of statins.…”

Section: Limitationsmentioning

confidence: 99%

The effects of additional ezetimibe treatment to baseline rosuvastatin on circulating PCSK9 among patients with stable angina

Zhang

Long

2017

J. Thorac. Dis.

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Background: Blood lipid management is one of the effective strategies for coronary heart disease, and statins are the first-line lipid-lowering drugs. Low density lipoprotein cholesterol (LDL-C) drop brings about cardioprotective effects. Proprotein convertase subtilisin kexin type 9 (PCSK9) is known to increase LDL-C, thus hazarding LDL-C reduction-induced benefits. To date, how PCSK9 responds to various lipidlowering strategies has not been fully clarified. Methods:This study involves patients with stable angina and aims to explore and clarify the short-term impacts of rosuvastatin and ezetimibe, alone or in combination, on circulating PCSK9. A total of 68 patients with stable angina were enrolled and 60 eligible patients were randomly assigned into 3 groups (20 subjects in each). Patients in different groups were treated for a period of 14 days with rosuvastatin 10 mg/d, ezetimibe 10 mg/d, and rosuvastatin 10 mg/d plus ezetimibe 10 mg/d, respectively. Concentrations of blood LDL-C and PCSK9 levels were measured at baseline and at the 14 th day after treatment. Results: Both rosuvastatin and ezetimibe could reduce the LDL-C levels, and rosuvastatin displayed a stronger cholesterol-lowering effect than ezetimibe. Moreover, when combined, they yielded even greater efficacy in lowering LDL-C, as compared with either rosuvastatin or ezetimibe mono-treatment (P<0.05).Rosuvastatin therapy (alone or combined with ezetimibe) caused significant rise in circulating PCSK9.Nevertheless, no significant growth of PCSK9 levels (P=0.558) was observed during ezetimibe treatment.At the 14 th day, no difference in PCKS9 levels was observed between the rosuvastatin group and the combination-therapy group (P=0.906).Conclusions: Rosuvastatin plus ezetimibe therapy is more effective in reducing LDL-C levels as compared with either rosuvastatin or ezetimibe mono-medication. Meanwhile, such combination strategy does not further increase the levels of circulating PCSK9 compared to rosuvastatin mono-intervention, thus maintaining maximal clinical benefits from lipid-lowering.

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Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia

Cited by 187 publications

References 27 publications

Rapid effects of simvastatin on lipid profile and C‐reactive protein in patients with hypercholesterolemia

Rapid effects of simvastatin on lipid profile and C‐reactive protein in patients with hypercholesterolemia

Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

The effects of additional ezetimibe treatment to baseline rosuvastatin on circulating PCSK9 among patients with stable angina

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