It should be noted that there is far less data about primary than about secondary prevention as most trials recruit patients either with overt coronary heart disease or who are at high risk for it.
Although older adults clearly benefit from aggressive statin therapy to a greater extent than younger patients, they are much less likely to receive a statin prescription than their younger counterparts. Possible reasons for the fact that older patients tend to receive fewer statin prescriptions than younger patients include:. It is clear that multiple studies support the use of statin therapy in elderly patients with, or at risk for, heart disease.
How should a clinician choose which statin to use? Before proceeding, a brief discussion reviewing the distinguishing pharmacological features of statins is warranted. In the United States there are presently six statins available: lovastatin Mevacor , pravastatin Pravachol and simvastatin Zocor —all available generically and by brand name; and atorvastatin Lipitor , lovastatin Mevacor , and rosuvastatin Crestor which are available by brand name only.
In general, rosuvastatin, atorvastatin and simvastatin are considered to be the most potent statins and fluvastatin, pravastatin and lovastatin less potent. Some authors, however, place simvastatin in the less potent group and pravastatin in the more potent group.
Statins have been found to have coronary heart disease and stroke lowering capabilities which do not directly correlate either with their LDL lowering or their HDL raising effects. In recognition of the pleiotropic effects of at least one statin, rosuvastatin, the U. Rosuvastatin is the most potent statin and has the longest half-life. Factoring in its low incidence of adverse effects and relatively low rate of drug-drug interactions further raises the potential usefulness of rosuvastatin for use in older adults, as will be further elucidated below.
Lipophilic statins penetrate muscle more easily than hydrophilic statins and are associated with a higher incidence of adverse effects, particularly myopathy, although reports of muscle toxicity, including rhabdomyolisis have been reported with all statins.
Hydrophilic statins include pravastatin and fluvastatin. Protein binding also plays a role in the potential for adverse effects of statins. Statins other than pravastatin are highly protein bound.
Decreases in serum protein levels, often seen in frail older adults may result in higher concentrations—and higher toxicity. Pravastatin, fluvastatin and rosuvastatin, the hydrophilic statins , are also the three statins not metabolized by the Cytochrome p 3A4 enzyme CYP3A4 , though fluvastatin and, to a lesser extent, rosuvastatin, which is largely excreted unchanged, 3 are metabolized by CYP2C9.
Pravastatin is not metabolized by the cytochrome P system at all and has the lowest risk of drug-drug interactions of all the statins. The medications most likely to affect statin metabolism and thereby increase the risk of adverse effects such as myopathy include, but are not limited to: amiodarone; fluconazole, ketoconazole and other azole anti-fungals; the non-dihydropyridine calcium channel blockers- diltiazem and verapamil; cyclosporine; danazol; the anti-arrhythmic dronedarone; erythromycin and other macrolide antibiotics; nefazodone; phenytoin; and the protease inhibitors.
Grapefruit juice also inhibits CYP 3A4 and can potentiate statin myotoxicity. The potential for toxicity works both ways. Statins co-administered with warfarin can result in elevated INRs.
They can also contribute to phenytoin and digoxin toxicity when given with these medications. While statins as a class of drugs are generally safe, they are associated with two primary types of adverse effects: asymptomatic elevation of liver enzymes, and myopathies.
There is no evidence that the incidence of these two side effects are associated with each other; that is, patients with elevations of liver enzymes are not more likely to experience myopathies, or vice versa. All statins are associated with elevations of alanine aminotransferase ALT and aspartate aminotransferase AST up to three times the upper limit of normal.
For patients with persistent elevations of liver enzymes, discontinuation or lowering the statin dose almost always effects a return of liver enzyme levels to normal.
Myopathy is the most common side effect associated with the use of statins and, since the withdrawal of cerivastatin Baycol from the market in after its use resulted in a large number of cases of rhabdomyolisis, myopathy is also the side effect of most concern to clinicians. Definitions of the term myopathy vary. Myopathy —a general term referring to any disease of muscles; myopathies can be acquired or inherited and can occur at birth or later in life.
Myalgia —muscle ache or weakness without creatine kinase CK elevation. Myositis —muscle symptoms with increased CK levels. Rhabdomyolysis — muscle symptoms with marked CK elevation typically substantially greater than 10 times the upper limit of normal [ULN] and with creatinine elevation usually with brown urine and urinary myoglobin.
For the purposes of this review, myopathy is used in this more general sense of any muscle-related disorder.
Older age, along with small size, female gender, preexisting liver, renal or endocrine disease are all patient-dependent risks for statin induced myopathy. Any statin can cause any muscle symptom-- from mild myalgias to rhabdomyolisis.
Fluvastatin and pravastatin, two relatively low potency statins that are not metabolized by CYP3A4, carry the lowest risk of rhabdomyolisis; high dose simvastatin 80 mg carries the highest risk. Along with high dosing, drug-drug interactivity highly impacts the myopathic potential of statins. When statins which are metabolized by CYP3A4 atorvastatin, lovastatin, and simvastatin , are given with CYP3A4 inhibitors, their metabolism is decreased, and the potential for toxicity increases.
Atorvastatin is less affected by CYP3A4 inhibitors than lovastatin or simvastatin. In addition to CYP3A4 effects, the risk for myopathy is also compounded when statins are given with other medications which cause myopathy. Cyclosporin and danazol fit into this category as well as being CYP3A4 inhibitors. In efforts to synergize lipid lowering effects, non-statin lipid lowering agents are often co-administered with statins.
Unfortunately some of these medications such as niacin and fibric acid derivatives also cause myopathy—fenofibrate less so than gemfibrozil. Alternatively, according to the NLA, statin therapy should be discontinued in patients who develop intolerable muscle symptoms regardless of CK level.
For most patients, myopathy symptoms induced by statin therapy resolve relatively quickly; however, the results of the PRIMO study showed that it may take up to 2 months for resolution of symptoms. While myopathy caused by statins can be mild and can be reversed when the medication is discontinued, it may present as rhabdomyolysis or severe muscle damage. These studies have shown that in patients with a prior statin intolerance, the use of another statin is both well tolerated and efficacious.
An alternative option is the use of nonstatin lipid-lowering agents in place of statin therapy. The use of fibrates and niacin as monotherapy has been associated with myopathy.
Therefore, bile acid resins may be the optimal choice in those patients without triglyceride abnormalities who cannot tolerate statin therapy. Alternatives with a lower potential to induce myopathy have been explored, including the use of fluvastatin extended release, low-dose rosuvastatin, every-other-day dosing of atorvastatin or rosuvastatin, and twice weekly rosuvastatin, though these regimens are not approved by the FDA.
Studies have not shown a correlation between intramuscular CoQ 10 levels and statin-induced myopathy. Additionally, randomized, controlled trials evaluating the use of CoQ 10 as prevention have yielded equivocal results. This agent contains lovastatin and has been tolerated in those patients with an aversion to standard statin treatment. Clinical studies have not yielded significant results.
Additionally, the role of vitamin D has been somewhat controversial, as low levels are associated with both myalgia and poor muscle function. Studies evaluating vitamin D supplementation as prevention have been limited in their design and require validation through a larger randomized, double-blind, placebo-controlled trial. Educating the patient on the warning signs and risks of myopathy can prevent serious complications.
While many patients may self-treat their symptoms with analgesics or pain relievers, any sudden unexplained muscle weakness or other symptoms should be conveyed to their physician.
Statins play a vital role in the prevention of atherosclerotic cardiovascular complications, and statin therapy continues to be a mainstay in treating patients with dyslipidemia. While some patients may elect to discontinue therapy after consulting their health care provider, many patients may be able to continue statins with proper management of the adverse effects. Pharmacists in the inpatient and outpatient setting may be directly involved in the monitoring of medication therapy and tolerability, and therefore should be aware of the signs and symptoms of statin-associated myopathy.
Proper assessment of patients will assist in the recognition of patients at risk. Knowledge of the currently available statins and their properties will enable pharmacists to provide appropriate recommendations for individualized treatment regimens. Once patients are initiated on statin therapy, pharmacists have the opportunity to monitor patient adherence, treatment response, and medication safety, in addition to providing ongoing patient education on statin therapy and its adverse effects.
Pharmacists should continue to counsel patients on the risk and warning signs of statin-associated myopathy, as the incidence underscores the need for pharmacists to play a direct role in the monitoring of statin therapy in the inpatient and outpatient setting. Updated April Accessed September 21, Narrative review: statin-related myopathy.
Ann Intern Med. Evidence-based management of statin myopathy. Curr Atheroscler Rep. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients—the PRIMO study. Cardiovasc Drugs Ther. For consumers. FDA: Limit use of 80 mg simvastatin. Updated June Accessed January 10, The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis.
Curr Opin Lipidol. Risk factors and drug interactions predisposing to statin-induced myopathy. It is advisable to monitor patients for signs and symptoms of muscle pain, tenderness or weakness, particularly during both the initial months of statin therapy and subsequent dose increases. Patients with additional risk factors e.
Statin treatment should be discontinued immediately if an elevated CK level is found i. The risk of myopathy or rhabdomyolysis with simvastatin alone is dose related; the incidence, determined from clinical trials, is approximately 0. This risk is increased with concomitant fibrates, as they alone can cause myopathy. Both had significant co-morbidity. To minimise the likelihood of interactions, lower starting doses of simvastatin and atorvastatin should be used in patients already on fibrates, cyclosporin, amiodarone, verapamil, and other potent CYP 3A4 inhibitors.
Diltiazem should not be co-prescribed with high doses of simvastatin or atorvastatin; and for all concurrent therapy, there should be closer monitoring.
0コメント