Niacin with statins

F Before initiating statin therapy, it is recommended to have baseline measurements of the lipoprotein profile and LFTs. If the LFTs are more than three times the upper limit of normal (ULN), statins should be avoided. If the LFTs are less than three times the ULN, statin therapy can be initiated, but the patient should be monitored closely. If LFTs become elevated, reversal of the transaminase elevation is common upon discontinuation of the statin. Some experts also recommend obtaining a baseline creatine kinase (CK) level. If the CK level is more than 10 times the ULN while on a statin, the statin should be discontinued. The combination of a statin with niacin or a fibrate should be used cautiously because of an increased risk of myopathy. Although most statins are taken at dinner or bedtime, atorvastatin can be taken at any time of the day due to its longer T /i ( 14 hours). Lovastatin should be taken with food because this increases its bioavailabilty. 

Niacin (11) is the most potent HDL-raising drug (20-30%) on the market, and also provides some reduction in TG and LDL-C levels. Clinical studies with niacin as monotherapy or in combination with statins have yielded marked reductions in... 

Statins Yes Reduces LDL Ila Ik with niacin Myositis, liver dysfunction, rhabdomyolysis with cerivastatin... 

Bile acid-sequestering resins Yes Reduces LDL n. Severe 11, with statin or niacin GI distress, hyperchloremic acidosis... 

Combination therapy with niacin and a statin has also been shown to produce clinical and angiographic benefits. Brown et al. (56) evaluated the effects of simvastatin in combination with niacin on patients with documented coronary disease in the HATS trial and demonstrated a significant reduction in nonfatal MI or death from cardiovascular causes compared to placebo, albeit with a relatively small number of patients. In the treatment arm, HDL cholesterol increased by 26% over the three years of treatment and was also associated with a slight regression (0.4%) in coronary mean percent stenosis in the proximal arteries by invasive arteriography the placebo arm experienced a 3.9% increase in stenoses. 

It is not yet clear whether the combination of statin and niacin will increase the incidence of diabetes. This is of significance as recent meta-analysis has shown that the association of incidence of diabetes with statin therapy remains uncertain. In particular the authors of the meta-analysis recommended that future statin trials should be designed to investigate whether statin treatment is associated with increased risk of induced diabetes (Rajpathak et al. 2009). Evaluation of the longer term impact of niacin s effect on insulin resistance and glucose metabolism awaits the results of longer-term clinical trials. Perhaps this may elicit or refute the diabetogenic effect of niacin. 

The impact of niacin in insulin sensitivity is important as the majority of those who needs to be treated with niacin will have a degree of insulin resistance (individuals with metabolic syndrome and type 2 diabetes). Furthermore, recent meta-analyses suggest that statin administration is associated with the degree of insulin resistance. 

Angiographic regression of coronary lesions with niacin-statin combination therapy (P<0.001 vs. placebo) clinical events reduced by 70% (P=0.03)... 

Helsinki Heart Study (15) have all demonstrated the benefit of lipid lowering using various hypolipidemic agents for prevention of initial cardiac events. Secondary prevention trials have unequivocally shown that lipid lowering therapy not only reduces acute coronary events and other clinical endpoints, but also results in angiographic improvement. These studies have used different classes of drugs (statins, fibrates, niacin, bile acid resins—alone and in combination) in both hyper- and normo-cholesterolemic patients with established CAD. 

Another treatment for cholesterol is niacin. The use of niacin predates the statins. Niacin is also known as nicotinic acid or vitamin B3. The name, niacin comes from nicotinic ac id and vitamin and was coined to avoid confusion and so that people would not think that the vitamin contained nicotine or that tobacco products contained vitamins. Niacin inhibits lipoprotein synthesis by preventing the secretion of very low density lipoprotein from the liver. Very low density lipoprotein is a precursor of low density lipoproteins (LDL). However there are several adverse side effects with niacin including flushing, warm skin, itching rash, constipation, nausea, hearthum, and problems with liver function. Because of these side effects, niacin is often used in a controlled release form [17] and even in this form is unsuitable for many patients. 

In general, niacin reduces LDL cholesterol from 5% to 25%, reduces triglycerides by 20% to 50%, and increases HDL cholesterol by 15% to 35% (Table 9-8). Niacin has been shown to reduce CHD events and total mortality31 as well as the progression of atherosclerosis when combined with a statin.31... 

Some patients, in particular those with genetic forms of hypercholesterolemia (Table 9-2), will require three or more drugs to manage their disorder. Regimens using a statin, resin, and niacin were found to reduce LDL cholesterol up to 75%.42 These early studies were conducted with lovastatin, so larger reductions would be expected with the more potent statins available today. 

Primary hypercholesterolemia (familial hypercholesterolemia, familial combined hyperlipidemia, type Ila hyperlipoproteinemia) is treated with BARs, statins, niacin, or ezetimibe. 

Regimens intended to increase HDL levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of hepatotoxicity or myositis. 

Crestor Astra-Zeneca) and lovastatin + niacin (Advicor Kos Pharmaceutical) — that can also cause rhabdomyolysis remain on the market. Although scientists agree that the other statins "seem to have essentially identical safety profiles and benefif-risk rafios," FDA said the ADRs associated with Baycol "have been reported significantly more frequently than for other approved statins." ... 

This combination is sometimes useful in treating patients with familial combined hyperlipidemia who are intolerant of niacin or statins. However, it may increase the risk of cholelithiasis. 

In a small (81 patients) retrospective analysis, patients on lipidlowering medication (statins, fibrates, or niacin derivatives) at the time of PCI had a significantly lower incidence of adverse events during the procedure, such as emboli and dissections, as compared to those not taking such agents (57). A high-total cholesterol, low-density lipoprotein, or ratio of low to high-density lipoprotein were also associated with increased adverse events,... 

It is well established that HMG-CoA reductase inhibitors and bile acid sequestrants can be used together safely, with a greater reduction in LDL cholesterol than is obtainable when either drug is used alone. Unfortunately, bile acid sequestrants are often poorly tolerated, which limits the usefulness of this combination. Relatively low doses of niacin, when used in combination with statins, produce a very attractive effect on the lipoprotein profile (Gardner et al., 1996 Stein et al., 1996) the ability of niacin to substantially increase HDL cholesterol is additive, with the profound reduction in LDL cholesterol produced by the statin, and there is also a moderate reduction in triglycerides. However,... 

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