Lipid-lowering therapy

The development of CHD is a lifelong process. Except in rare cases of severely elevated serum cholesterol levels, years of poor dietary habits, sedentary lifestyle, and life-habit risk factors (e.g., smoking and obesity) contribute to the development of atherosclerosis.3 Unfortunately, many individuals at risk for CHD do not receive lipid-lowering therapy or are not optimally treated. This chapter will help identify individuals at risk, assess treatment goals based on the level of CHD risk, and implement optimal treatment strategies and monitoring plans. 

Bexarotene—causes severe hyperlipidemia in majority of patients treated may require concomitant lipid-lowering therapy... 

The primary goal of lipid-lowering therapies in CKD is to decrease the risk for progressive atherosclerotic cardiovascular disease (Table 76-1). 

Although the plasma concentrations of Lp(a) are, in general, refractory to conventional lipid-lowering therapy, any diet or drug that lowers LDL levels may... 

As discussed above, obesity is associated with dyslipidemia, a condition where high levels of low-density lipoprotein cholesterol (LDL-C) is common. Elevated LDL-C is strongly associated with an elevated risk of coronary artery disease and for this reason a number of lipid-lowering therapies that target LDL-C have been developed. These include bile-acid sequestrants (BAS), statins (HMG-CoA reductase inhibitors), cholesterol absorption inhibitors, and fibrates. ... 

Concomitant lipid-lowering therapy- When administering a bile acid resin and fluvastatin, administer fluvastatin at bedtime, at least 2 hours following the resin. 

Concomitant lipid-lowering therapy - Generally avoid use of lovastatin with fibrates or niacin. If lovastatin is used in combination with gemfibrozil, other fibrates, or lipid-lowering doses (1 g/day or more) of niacin, the dose of lovastatin should not exceed 20 mg/day. 

Concomitant lipid-lowering therapy-The effect of rosuvastatin on LDL-C and total-C may be enhanced when used in combination with a bile acid-binding resin. If rosuvastatin is used in combination with gemfibrozil, limit the dose of rosuvastatin to 10 mg once daily. 

Kastelein JJ (2003) The future of lipid-lowering therapy the big picture. Neth J Med 61(Suppl 5) 35—39... 

Many of the hyperlipidemic states are associated with the development of xanthomas. These lesions, which are produced by deposition of lipid in tendons or skin, may be painful or cosmetically unacceptable to the patient. Because xanthomas regress with lipid-lowering therapy, this provides another indication for treatment. 

Supplementation with the antioxidant vitamins ascorbic acid (250 mg) and mixed natural tocopherols (50 IU on alternate days) may be beneficial. Higher doses may vitiate the impact of lipid lowering therapy. Other naturally occurring antioxidants such as resveratrol, 3-catechin, selenium, and various carotenoids found in a variety of fruits and vegetables may provide additional antioxidant defense. Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Daily supplementation with up to 2 mg of folic acid plus other B vitamins is also recommended. 

Several randomized clinical trials of lipid lowering therapy with statins have been conducted in patients with acute... 

Aronow HD, Topol EJ, Roe MT, et al, Effect of lipid-lowering therapy on early mortality after acute coronary syndromes an observational study. Lancet 2001 357 1063-1068. 

Smith CS, Cannon CP McCabe CH, Murphy SA, Bentley J, Braunwald E, Early initiation of lipid-lowering therapy for acute coronary syndromes improves compliance with guideline recommendations observations from the Orbofiban in Patients with Unstable Coronary Syndromes (OPUS-TIMI I 6) trial. Am Heart J 2005 149 444-450. 

Nissen SE, Tuzcu EM, Schoenhagen R et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis a randomized controlled trial. JAMA 2004 291 1071-1080. 

Pitt B, Waters D, Brown WV et al. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators, N Engl J Med 1999 341 70-76. 

Aronow HD, Novaro GM, Lauer MS, et al. In-hospital initiation of lipid-lowering therapy after coronary intervention as a predictor of long-term utilization a propensity analysis. Arch Intern Med 2003 163 2576-2582. 

A meta-analysis was performed on randomized trials assessing lipid-lowering therapy in 698 patients with PAD who were treated with a variety of therapies, including diet, cholestyramine, probucol, and nicotinic acid, for four months to three years (8). There was a significant difference in total mortality [0.7% in the treated patients, as compared with 2.9% in the patients given placebo (p = NS)], with an additional reduction in disease progression, as measured by angiography and the severity of claudication. 

Two studies evaluated the effects of lipid-lowering therapy on clinical endpoints in the leg. The Program on the Surgical Control of the Hyperlipidemias was a randomized trial of partial ileal-bypass surgery for the treatment of hyperlipidemia in 838 patients (9). After five years, the relative risk (RR) of an abnormal ankle-brachial index value (ABI) was 0.6 (95% Cl, 0.4 to 0.9, absolute risk reduction, 15% points, p < 0.01), and the RR of claudication or limb-threatening ischemia was 0.7 (95% Cl, 0.2 to 0.9, absolute risk reduction, 7% points, p < 0.01), as compared with the control group. 

This is an adequate basis for a therapy, although the biochemical pathogenetic correlations between increased blood lipids and arteriosclerosis or other diseases are largely unknown. In any case a lipid lowering therapy will be useful only if started early and understood as long-term therapy. 

Lipid-lowering therapy may not be urgent and consideration should be given to holding therapy until any acute liver episode has passed and the patient is compensated. 

Patients must be monitored carefnlly for signs of myopathy and hepatotoxicity. Elevations of transaminases as a possible pharmacodynamic effect of lipid-lowering therapy should be considered. Liver function tests (LFTs) shonld be monitored to identify possible hepatotoxicity. Statins shonld be withheld or changed if elevations in transaminases are persistently more than three times ULN or are accompanied by other signs of liver disease that might be iatrogenic. In addition, the patient mnst be adequately monitored in order to identify ... 

Brown WV (2007) Expert commentary the safety of fibrates in lipid-lowering therapy. Am J Cardiol 99 19C-21C. 

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