Statin therapy

Cannon CP et al (2006) Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol 48 438-445... 

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

To control risk factors and prevent major adverse cardiac events, statin therapy should be considered in all patients with ischemic heart disease, particularly in those with elevated low-density lipoprotein cholesterol. In the absence of contraindications, angiotensin-converting enzyme inhibitors should be considered in ischemic heart disease patients who also have diabetes melli-tus, left ventricular dysfunction, history of myocardial infarction, or any combination of these. Angiotensin receptor blockers... 

All ACE-I + diuretic or ARB blood pressure lowering Peridopril 2-8 mg daily Indapamide 1.25-5 mg daily Statin therapy ... 

Baseline CK should be obtained in all patients prior to starting statin therapy. Follow-up CK should only be obtained in patients complaining of muscle pain, weakness, tenderness, or brown urine. Routine monitoring of CK is of little value in the absence of clinical signs or symptoms. Patient assessment for symptoms of myopathy should be done 6 to 12 weeks after starting therapy... 

Ezetimibe reduces LDL cholesterol by an average of 18% (Table 9-8). However, larger reductions can be seen in some individuals, presumably due to higher absorption of cholesterol. These individuals appear to have a blunted response to statin therapy. Ezetimibe lowers triglycerides by 7% to 9% and modestly increases HDL cholesterol. 

Compared with monotherapy, combination therapy is relatively unstudied in terms of the effects on CHD event reduction and may reduce patient compliance through increased side effects and increased costs. When used appropriately and with proper precautions, however, they are effective in normalizing lipid abnormalities, particularly in patients who cannot tolerate adequate doses of statin therapy for more severe forms of dyslipidemia. 

Damas JK, Boullier A, Waehre T, et al. Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy. Arterioscler Thromb Vase Biol 2005 25 2567-2572. 

Apolipoprotein AIV (apo AIV) is produced in the intestine and is found in chylomicrons, VLDL and HDL. It may modulate enzymes involved in lipoprotein metabolism and may serve as a saturation signal [49]. In a study with 144 participants the apo AIV His360Glu polymorphism showed no significant effect on cholesterol lowering in response to statin therapy [50]. 

Ezetimibe interferes with the absorption of cholesterol from the brush border of the intestine, a novel mechanism that makes it a good choice for adjunctive therapy. It is approved as both monotherapy and for use with a statin. The dose is 10 mg once daily, given with or without food. When used alone, it results in an approximate 18% reduction in LDL cholesterol. When added to a statin, ezetimibe lowers LDL by about an additional 12% to 20%. A combination product (Vytorin) containing ezetimibe 10 mg and simvastatin 10, 20, 40, or 80 mg is available. Ezetimibe is well tolerated approximately 4% of patients experience GI upset. Because cardiovascular outcomes with ezetimibe have not been evaluated, it should be reserved for patients unable to tolerate statin therapy or those who do not achieve satisfactory lipid lowering with a statin alone. 

Topol EJ. Intensive statin therapy - a sea change in cardiovascular prevention. N Engl ] Med 2004 350 1562. ... 

Murphy Ml, Dominiczak MH. Efficacy of statin therapy possible effect of phenytoin. Postgrad Med J 1999 75 359-60. 

Evidence-based pharmacotherapy provides a succinct appreciation of the benefits of a drug, but rarely takes into account the patient s quality of life. Eor instance, intensive statin therapy is recommended because it reduces the incidence of cardiovascular death (odds ratio 0.86), myocardial infarction (odds ratio 0.84), and stroke (odds ratio 0.82) however, the increased risks for any adverse event (odds ratio 1.44), for abnormalities on liver function testing (odds ratio 4.48), for elevations in CK (odds ratio 9.97) and for adverse events requiring discontinuation of therapy (odds ratio 1.28) are less often taken into account by the prescriber. This example emphasises that individualisation is of the utmost importance to keep an acceptable benefit/risk ratio (Clin Ther 2007 29 253-60). The benefits of evidence-based pharmacotherapy may be obtained whenever concordance/compliance of the patient is adequate. However, concordance rate is slightly higher than 30% for chronic conditions, such as hypertension (Curr Hypertens Rep 2007 9 184-9), indicating that the patient has to be educated about the use of drugs, and therapy has to be individualised. 

Contemporary management of lipid disorders The evolving importance of statin therapy. Clin Courier 1998 28(No.35) l-7. 

In 14 asymptomatic patients statin therapy worsened left ventricular diastolic function co-enzyme Q10 supplementation produced improvement. There were several limitations of this study, including a small sample size and the lack of a control arm, but the patients did serve as contemporary controls for themselves. Because baseline concentrations of co-enzyme Q10 do not predict dysfunction, routine concomitant co-enzyme Q10 administration, especially in patients at risk, may be prudent (5). 

Emerging data associate statins with a reduced risk of Alzheimer s disease however, two women had significant cognitive impairment temporally related to statin therapy (18). One took atorvastatin, and the other first took atorvastatin then simvastatin. Cognitive impairment and dementia as potential adverse effects associated with statins has been reviewed (17). 

Rajabally YA, Varakantam V, Abbott RJ. Disorder resembling Guillain-Barre syndrome on initiation of statin therapy. Muscle Nerve 2004 30(5) 663-6. 

Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients—the PRIMO Study. Cardiovasc Drugs Ther 2005 19(6) 403-14. 

Chazerain P, Hayem G, Hamza S, Best C, Ziza JM. Four cases of tendinopathy in patients on statin therapy. Joint Bone Spine 2001 68(5) 430-3. 

Noel B, Panizzon RG. Lupus-hke syndrome associated with statin therapy. Dermatology 2004 208(3) 276-7. 

Rondina MT, Muhlestein JB. Early initiation of statin therapy in acute coronary syndromes a review of the evidence. J Interv Cardiol. 2005 18 55-63. 

Schwartz GG, Olsson AG. The case for intensive statin therapy after acute coronary syndromes. Am J Cardiol. 2005 96 45F-53F. 

Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005, 352(l) 20-28. 

Ziajka, P. E., Reis, M., Kreul, S., and King., H. (2004) Initial low-density lipoprotein response to statin therapy predicts subsequent low-density lipoprotein response to the addition of ezetimibe. Am. J. Cardiol. 93, 779-780. 

Wienbergen H, Gift AK, Schiele R, et al. MITRA PLUS Study Group. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003 92 285-288. 

T ble 1 Design features (A) and major cardiovascular endpoints (B) in controlled trials of statin therapy... 

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