Stroke statins

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. ... 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Jonsson N, Asplund K. Does pretreatment with statins improve clinical outcome after stroke A pilot case-referent study. Stroke 2001 32 1112-1115. 

Favorable outcome of ischemic stroke in patients pretreated with statins. Stroke 2004 35 1117-1121. 

Yoon SS, Dambrosia J, Chalela J, Ezzeddine M, Warach S, Haymore J, Davis L, Baird AE. Rising statin use and effect on ischemic stroke outcome. BMC Med 2004 2 4. 

Montaner J, Chacon R Krupinski J, et al. Safety and efficacy of statins in the acute phase of ischemic stroke the mistics trial. Stroke 2004 35 293. 

Gertz K, Laufs U, Lindauer U, Nickenig G, Bohm M, Dirnagl U, Endres M. Withdrawal of statin treatment abrogates stroke protection in mice. Stroke 2003 34 551-557. 

Hyperlipidemia has not clearly been established as a risk factor for stroke, although it is a modifiable risk factor for coronary heart disease. Recent studies show that statin use may reduce the incidence of a first stroke in high-risk patients (e.g., hypertension, coronary heart disease, or diabetes) including patients with normal lipid levels. A recent meta-analysis showed a 25% risk reduction for fatal and non-fatal strokes with statin use.4 Patients with a history of MI, elevated lipid levels, diabetes, and... 

The National Cholesterol Education Program considers ischemic stroke or TIA to be a coronary risk equivalent and recommends the use of statins in... 

There is some evidence that statins can reduce the risk of stroke and even senile dementia. Consequently, there is current clinical discussion as to whether statins should be recommended for all patients with an increased risk of stroke and possibly for protection against senile dementia. 

Statins are a group of cholesterol lowering drugs that have been shown to be beneficial as published in 1997. In patients with ischaemic heart disease, the number of stroke events was reduced by 30% compared with placebo. 

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. 

The statins may lower the risk of CHD by decreasing inflammation, an important component of atherogene-sis. Lovastatin decreased elevated plasma levels of C-reactive protein, a marker for cellular inflammation, and acute coronary events in patients with relatively low plasma cholesterol levels. Recent studies also suggest that use of statins may decrease the risk of stroke, dementia, and Alzheimer s disease and may improve bone... 

Drugs to lower cholesterol called statins reduce the risk of a heart attack by 20-30 percent and stroke by about 17 percent. 

Although it is not exactly clear how much these agents can reduce the risk of a major cardiac event (e.g., infarction, stroke), these drugs will probably remain the first choice for people with certain hyper-lipidemias (e.g., increased triglycerides). These drugs are likewise advocated for mixed hyperlipidemias that are common in metabolic disorders such as type 2 diabetes mellitus (see Chapter 32).32,141 Certain fibrates can be used with other drugs, such as statins, to provide more comprehensive pharmacologic control of certain lipid disorders.30,147... 

The 4S (16), CARE (17), and LIPID (18) studies demonstrated a reduction in stroke in patients with known CHD. However, manifest CHD was necessary for inclusion in these trials. The HPS (I I) showed a reduction in subsequent vascular events (but not recurrent stroke) in patients who had previous stroke but no previous clinical manifestations of CHD—from 23.6% to 18.7% (P = 0.001). At this time, guidelines usually support statin therapy in patients with previous stroke, although it is noted that stroke patients included in HPS were younger, less likely to be hypertensive, and differed in other features from usual stroke patients. 

Should all people with diabetes receive a statin The answer is an emphatic yes in those who already have CHD, stroke, or peripheral arterial disease. Guidelines differ on whether all those with diabetes but no clinical vascular disease should also be treated. This is recommended in many countries, whereas others suggest an individual approach based on the estimated risk of future events. 

The reduction in stroke observed in long-term statin trials despite the lack of association between cholesterol levels and stroke in most epidemiological and observational studies. 

These elfects on cerebrovascular events and on intermittent claudication suggest that simvastatin and other elfective lipid-lowering treatments may have a general antiatherosclerotic elfect not limited to the coronary bed. Definitive evidence on the elfects of statin therapy in stroke prevention and peripheral vessel disease is likely to be provided by the Heart Protection Study (MRC/BHF Heart Protection Study Collaborative Group, 1999). As noted above, this UK study has randomized over 20,000 patients aged up to 80 to simvastatin 40 mg or placebo, and the 5-year treatment period is scheduled for completion in 2001. Among these patients are 3288 patients with a history of cerebrovascular disease. Because of its size and the broad array of patient types randomized, this study should also provide reliable evidence of the elfect of simvastatin on coronary morbidity and mortality in women, elderly patients, patients with low levels of LDL and HDL cholesterol, patients with peripheral vascular disease, and diabetic patients with or without coronary disease (MRC/BHF Heart Protection Study Collaborative Group, 1999). 

Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease and stroke systemic review and meta-analysis. Br. Med. J., 2003, 326, 1423-1430. 

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