Hyperlipidemias and Atherosclerotic Cardiovascular Disease ________________________________________
STATIN DOSES REQUIRED TO REDUCE LDL TO BASELINE GOAL
Agent
Percent Reduction in LDL Necessary to Reach Goal 20% to 25% 26% to 30% 31% to 35% 36% to 40% 41% to 50% 51% to 55%
Rosuvastatin Atorvastatin Simvastatin Lovastatin Pravastatin Fluvastatin
— — — —
— —
—
5 mg
10 mg 40 mg 80 mg a
20–40 mg
10 mg 20 mg 40 mg 40 mg 80 mg
20 mg 40 mg 80 mg 80 mg
80 mg
10 mg 20 mg 20 mg 40 mg
— — — —
— — — —
10 mg 20 mg
— —
Pitavastatin — a Increasing to 80 mg is not routinely recommended. Reserve for patients who have been taking this dose for more than 12 consecutive months without evidence of myopathy. Source: [14; 24; 109; 141] Table 5 — 1–4 mg —
Statins are well absorbed through the gastrointestinal system and are metabolized in the liver by cytochrome P450. Metabolites are eliminated through the bile and excreted in the feces and, to a much lesser extent, by the kidneys. These drugs should not be used in patients with active liver disease and should be used cautiously at lower doses in patients with kidney disease [109]. Statins are effective in the prevention of ASCVD [67; 150; 151]. In a 2009 review and meta-analysis, these drugs are referred to as “the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments” [152]. Analysis of the risk-benefit ratio of statins after one year of treatment reveals that an estimated 1,587 cases of fatal and non-fatal cases of ASCVD were prevented against 3.4 cases of rhabdomyolysis [140; 153; 154]. Randomized controlled trials across differing risk categories of patients have shown that statins confer significant relative risk reductions in cardiovascular events and all-cause mortality [235]. Adverse Effects Dizziness (7%), diarrhea (4.5%), nausea/vomiting (3%), and abdominal cramps (3%) are among the most frequently reported adverse effects. Statins are contraindicated during pregnancy and lactation [128]. Statins are associated with hepatotoxicity and elevated transaminases in 1% to 2% of patients [128]. However, in 2014, the FDA concluded that the rate of liver injury associated with statin use is rare enough that routine liver enzyme screening while using statins is not needed. It is recommended that liver enzyme tests be performed before statin use begins and then only if there are symptoms of liver damage, including extreme fatigue, loss of appetite, right upper abdominal discomfort, dark urine, or jaundice [155; 156].
The FDA has also noted a small increase in the risk for type 2 diabetes while taking statins. It is noted that there may be a need to assess blood sugar levels after beginning statin use, especially in those with other risk factors [156]. The incidence of myopathy, characterized by muscle pain, weakness, and grossly elevated creatine kinase levels (>10 times the upper limit of normal), with the use of a statin alone is reported in 0.1% to 0.2% of patients [128]. Yet, studies have indicated that the occurrence of statin-induced myopathy may be much higher than originally reported, as high as 10% to 15% of patients treated with statins [140; 157]. A deficiency in coenzyme Q10 (CoQ10), a product of the HMG-CoA reductase pathway selectively inhibited by statins, has been proposed as a possible mechanism of statin-related myotoxicity. Although CoQ10 serum levels are below normal in patients taking statins, there is no direct correlation between myotoxicity and CoQ10 levels in muscle cells. Furthermore, studies of supplementation with CoQ10 to prevent myopathy in patients taking statins have not found conclusive evidence of effectiveness [140; 158; 159; 160]. Alternatively, other studies have shown that the inhibition of HMG-CoA reductase by statins inhibits mitochondrial function, increases intracellular calcium, and activates apoptosis (i.e., programmed cell death) [161]. This latter mechanism is being further investigated and may play a crucial role in the development of lipid-lowering drugs with an even higher safety profile [140]. The occurrence of rhabdomyolysis, defined as skeletal muscle necrosis with release of potentially toxic muscle cell components into the general circulation, has been rarely reported. Possible complications of rhabdomyolysis include myoglobinuric acute renal failure, disseminated intravascular coagulation, hyperkalemia, and cardiac arrest. The risk of myopathy or rhabdomyolysis increases with higher statin plasma levels, which can be the result of higher doses, decreased hepatic clearance, or drug interactions [109; 156; 162].
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MDAK1526
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