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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statins reduce coronary and cerebrovascular mortality and morbidity in middle-aged individuals. Until recently, their efficacy and safety in elderly people had not yet been firmly established. PROSPER was a controlled, randomised study involving 2,804 men and 3,000 women aged 70-82, with a history of, or risk factors for cardiovascular disease. Their baseline cholesterol level was 135-350 mg/dl; they were randomised to either 40 mg pravastatin per day, or matching placebo. Average follow-up was 3.2 years. The primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Pravastatin lowered LDL-cholesterol (-34%), and reduced the incidence of the primary endpoint (-15%; CI 95%: 3-26%; p = 0.014). Coronary death and non-fatal myocardial infarction risk was also reduced (-19%; p = 0.006), and mortality from coronary disease fell by 24% (p = 0.043). The risk for stroke, however, was unaffected (p = 0.8), whereas the incidence of transient ischemic attacks was reduced by 25%, which was (marginally) insignificant (p = 0.051). Pravastatin had no effect on cognitive functions or incapacity. New cancers were more frequent amongst pravastatin-treated individuals (+25%; p = 0.020). However incorporation of this new data in a meta-analysis of all pravastatin and all statin trials revealed no overall increase of cancer risk.
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PMID:[The PROSPER Study (PROspective study of pravastatin in the elderly at risk)]. 1263 40

HMG-CoA reductase inhibitors (statins) have been established as the dominant treatment for coronary heart disease (CHD). This dominance is based on an impressive body of clinical trial evidence showing significant benefits in primary prevention of cardiovascular events in individuals at risk for CHD and in secondary prevention of such events in patients with CHD and high or normal plasma cholesterol levels. There is, however, significant room for improvement in the treatment of CHD with respect both to drug efficacy and to the disparity between evidence-based medicine and actual clinical practice particularly in relation to treatment strategies for the elderly. Current statins fall short of requirements for 'ideal' lipid-lowering treatment in several respects; 'super' statins and other agents currently in development may satisfy more of these requirements. Moreover, available therapies are not applied optimally, because of physician nonacceptance and/or patient noncompliance; thus, the majority of patients with CHD or its risk factors still have cholesterol levels that exceed guideline targets. There is also evidence that older patients with CHD, or at high risk of CHD, are undertreated - possibly because of concerns regarding the increased likelihood of adverse events or drug interactions or doubts regarding the cost effectiveness of statin therapy in this population. This group is of particular clinical relevance, since it is showing a proportionate rapid expansion in most national populations. To address their potential healthcare needs, the ongoing Pravastatin in the Elderly at Risk (PROSPER) study is assessing the effects of pravastatin in elderly patients (5804 men and women aged 70-82 years) who either have pre-existing vascular disease or are at significant risk for developing it, with the central hypothesis that statin therapy (pravastatin 40 mg/day) will diminish the risk of subsequent major vascular events compared with placebo. After a 3.2-year treatment period, a primary assessment will be made of the influence of statin treatment on major cardiovascular events (a combination of CHD death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Optimal deployment of the currently available agents and of newer agents (no matter how well they satisfy requirements for ideal treatment) ultimately depends on the establishment of an evidence base and may require far-reaching educational programmes that change the way risk factor management is viewed by caregivers and patients alike.
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PMID:Statin therapy in the elderly: does it make good clinical and economic sense? 1264 82

Statins inhibit cholesterol biosynthesis and protect against ischaemic stroke. It has become increasingly apparent that the beneficial effects of statin therapy may extend beyond lowering of serum cholesterol. The present study was done to explore possible pleiotropic statin effects at the level of the cerebral vascular smooth muscle. Lovastatin, lovastatin acid, simvastatin and pravastatin, were added to segments of the rat basilar artery and effects on contraction and Ca2+ handling were examined. Pravastatin had no effect on contraction. Simvastatin, lovastatin, and, to a lesser degree, lovastatin acid, caused relaxation (IC50=0.8, 1.9 and 22 micromol/l) of both intact and denuded arteries precontracted with 5-HT or high-K+. This effect was not reversed by mevalonate, suggesting that it was not related to cholesterol or isoprenoid metabolism. Relaxation was associated with a reduction of the intracellular Ca2+ concentration measured with Fura 2 and with a reduced Mn2+ quench rate, suggesting a direct effect on ion channels in the smooth muscle cell membrane. Current measurements in isolated and voltage clamped basilar artery muscle cells demonstrated that both lovastatin and lovastatin acid inhibit L-type Ca2+ current. We propose that lipophilicity is an important factor behind the effects of statins on vascular tone and that Ca2+ current inhibition is the likely mechanism of action.
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PMID:Lovastatin induces relaxation and inhibits L-type Ca(2+) current in the rat basilar artery. 1296 37

Stroke is a heterogeneous disorder with significantly high morbidity and mortality. The relationship between serum cholesterol level and the incidence of stroke remains controversial. Recent evidence from primary and secondary prevention trials suggests that treatment with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors may reduce the incidence of stroke in patients with coronary artery disease (CAD). In this review, we attempt to outline and describe the potential mechanisms of HMG-CoA reductase inhibitors in the prevention of stroke. In addition to their lipid-lowering action HMG-CoA reductase inhibitors appear to exert their beneficial effects by various nonlipid-lowering mechanisms including anti-inflammatory effects, effect on endothelial function and coagulation cascade. Treatment with HMG-CoA reductase inhibitors is associated with decreased progression, plaque stablization and even regression of atheromatous plaque in the carotid arteries. HMG-CoA reductase inhibitors also inhibit the coagulation cascade at various levels such as activation of prothrombin, factor V, factor X and liberation of tissue factor in response to vascular injury. Inhibition of fibrinolysis occurs secondary to inhibition of plasmin generation. Pravastatin therapy is associated with a reduction in the size of aortic atheroma which is an independent risk factor for stroke. Lastly, left ventricular dysfunction after acute myocardial infarction is associated with an increased risk of stroke and HMG-CoA reductase inhibitors may indirectly decrease the incidence of stroke by reducing coronary events. Most of these effects are independent of the cholesterol-lowering effects of HMG-CoA reductase inhibitors. In conclusion, HMG-CoA reductase inhibitors may have a role in primary prevention of stroke in patients with CAD.
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PMID:How do HMG-CoA reductase inhibitors prevent stroke? 1472 94

Statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals but their efficacy and safety in elderly people has not been confirmed. Several clinical trials including the Cholesterol and Recurrent Events (CARE) and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), have sub-analysed their results for the 'elderly' cohort, but the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial is the first trial to specifically evaluate the benefits of statin therapy on vascular risk in elderly men and women. The results have shown that pravastatin, given for 3 years, reduced the risk of coronary heart disease in elderly individuals. Within this same time frame, there was no significant benefit on the risk reduction of stroke but there was a trend to reduce the risk of transient ischemic attacks. It was discovered that those patients with the lowest baseline high-density lipoprotein cholesterol gained the most benefit from the intervention. Drug interactions between pravastatin and the concomitant medications seen in this elderly cohort, was not a significant clinical issue. Therefore, PROSPER extends to elderly individuals the treatment strategy currently used in middle-aged people.
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PMID:Preventing the next event in the elderly: the PROSPER perspective. 1498 Feb 31

The role of cholesterol in coronary heart disease (CHD) and stroke in elderly persons is controversial. Statin studies have generally included mostly middle-aged men, been targeted at either primary or secondary prevention, and lasted 5-6 years. In contrast, the PROspective Study of Pravastatin in the Elderly at Risk was a double-blind, randomized, placebo-controlled primary and secondary prevention trial that examined the effects of pravastatin 40 mg/d on the risk of CHD, cerebral vascular events, and cognitive function over 3 years in 5804 high-risk elderly persons (mean age 75 years; 52% women). Pravastatin therapy significantly improved lipid levels: low-density lipoprotein cholesterol (-34%), high-density lipoprotein cholesterol (+5%), and triglycerides (-13%) and produced no adverse effects on liver function tests or myopathy. Moreover, pravastatin reduced the primary end point (CHD death, nonfatal myocardial infarction, and stroke) by 15% (p=0.014), including 24% reduction in CHD death (p=0.043) and 19% reduction in combined CHD death and nonfatal myocardial infarction (p=0.006). Although transient ischemic attacks fell by 25% (p=0.05) with pravastatin, there were no significant reductions in stroke or improvements in cognitive function. These results demonstrate the benefits of pravastatin in primary and, particularly, secondary prevention in elderly populations and further support the benefits of statin therapy in high-risk elderly persons.
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PMID:A prospective study of pravastatin in the elderly at risk: new hope for older persons. 1513 25

Cardiovascular disease and its clinical sequelae remain the leading causes of morbidity and mortality in many regions of the world. Dyslipidemia is a critical risk factor to intercept in both the primary and secondary prevention of acute cardiovascular events. The prospective, placebo-controlled clinical trials conducted with statins over the course of the past 15 years have conclusively demonstrated that these drugs significantly reduce risk for fatal and nonfatal myocardial infarction, ischemic stroke, unstable angina, and frequency of myocardial ischemia, as well as cardiovascular and all-cause mortality. Of considerable interest is the fact that, even under the exquisitely controlled circumstances of a clinical trial, endpoint reductions in these trials typically occur in the range of 20% to 35%. Understandably, much attention is now being focused on deriving the pharmacologic means by which to further increase the magnitude of endpoint reduction. Epidemiologic investigation has demonstrated that the relationship between cholesterol and risk for atherosclerotic disease is a continuous one. Consequently, it is reasonable to assume that more aggressive reductions of low-density lipoprotein (LDL) cholesterol might result in even greater reductions of cardiovascular event rates and atheromatous plaque progression than heretofore observed. Two recent clinical trials, Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT), prospectively tested and confirmed the validity of more aggressive LDL cholesterol lowering in high-risk patients with established coronary artery disease.
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PMID:Low-density lipoprotein reduction in high-risk patients: how low do you go? 1529

The Prospective Pravastatin Pooling (PPP) Project was a prospectively defined collaboration of three randomized, placebo-controlled, long-term, monotherapy (40 mg/d) trials of the lipid-lowering agent pravastatin. A pooled database of 19,768 participants with a mean of 5.2 years of follow-up was created, providing the investigators with over 100,000 patient-years of experience to address questions on total and cause-specific mortality, coronary incidence, stroke, and safety. One trial (West of Scotland Coronary Prevention Study) was primary prevention and two (Cholesterol and Recurrent Events and Long-term Intervention with Pravastatin in Ischemic Disease) were secondary prevention. Pravastatin was shown to safely reduce all-cause mortality, fatal and nonfatal coronary events, and stroke events in patients with a broad range of patient characteristics.
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PMID:Lessons learned from the prospective pravastatin pooling project. 1529 3

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.
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PMID:Are Canadian guidelines for cholesterol lowering in high-risk patients optimal? 1568 8

Inflammation is pivotal in atherosclerosis, and C-reactive protein (CRP) is an inflammatory marker that predicts cardiovascular events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial compared the standard lowering of low-density lipoprotein (LDL)-cholesterol with pravastatin 40 mg/day, with the intense lowering of LDL-cholesterol with atorvastatin 80 mg/day on atheroma volume in patients with coronary artery disease, and showed that the atheroma progressed by 2.7% in the pravastatin group, and remained unchanged in the atorvastatin group. At 18 months follow-up, the CRP levels were reduced from a baseline level of 2.8 mg/l to 1.8 mg/l by atorvastatin, whereas pravastatin had little effect, and there was a good correlation between both the ultrasonographic progression of disease and the reduction in CRP levels. The Pravastatin or Atorvastatin Evaluation and Infection Therapy--Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial compared the long-term effects of the standard lowering of LDL-cholesterol with pravastatin, with the intense lowering of LDL-cholesterol with atorvastatin in patients with an acute coronary syndrome. The primary end point was the first of death, myocardial infarction, unstable angina requiring hospitalisation, revascularisation or stroke, and, at the end of 2 years, was greater in the pravastatin than the atorvastatin group (26.3 versus 22.4%, respectively). Patients with CRP levels of 2 mg/l had lower rates of recurrent myocardial infarction or death from coronary causes than patients with higher levels. Further analysis should be undertaken to assess cardiovascular risk at different levels of CRP, including assessing cardiovascular risk at different levels in men and women. Definitive results about the importance of lowering CRP levels are not likely to be obtained until the results of the Justification for Use of Statins in Primary Prevention, an Intervention Trial in Evaluating Rosuvastatin (JUPITER) study are published.
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PMID:Relating statin therapy to C-reactive protein levels. 1608 47


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