The safety and efficacy of achieving very low LDL-cholesterol concentrations with high dose statin therapy

PURPOSE OF REVIEW: The benefits of lipid lowering with statins are established in patients with or at risk for coronary artery disease. Recent trials with high doses of potent statins have examined treating to very low levels of LDL-cholesterol. Concerns have been raised about the safety of this strategy. This review examines the safety and efficacy of treating to very low LDL-cholesterol. RECENT FINDINGS: Four clinical trials, Treating to New Targets (TNT) and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) in stable coronary artery disease and Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT)-TIMI 22 following acute coronary syndromes, have examined intensive statin therapy compared to moderate statin therapy. These trials and a meta-analysis demonstrated that intensive statin therapy reduces cardiovascular events. Subsequent analyses from these trials suggest that very low levels of LDL-cholesterol can be achieved safely and may improve clinical outcomes. A note of caution regarding hemorrhagic events following stroke with intensive statin therapy was raised by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial despite impressive reductions in cardiovascular events. SUMMARY: A growing body of evidence suggests progressive benefit for lowering LDL-cholesterol aggressively with intensive statin therapy in coronary artery disease. Future trials will be needed to define whether there is a level of LDL-cholesterol beyond which further benefit is not seen or safety concerns emerge.     

Statin therapy for prevention and treatment of acute and chronic cardiovascular disease: update on recent trials and metaanalyses

PURPOSE OF REVIEW: To summarize the evidence from recent clinical trials and metaanalyses on the efficacy of statin therapy to reduce death, myocardial infarction and stroke, and to review the effects of statins in patients with low LDL cholesterol, diabetes, end-stage renal disease, and acute coronary syndrome. RECENT FINDINGS: In large metaanalyses of randomized controlled trials relative risk reductions from statins compared with placebo for patients with manifest or with risk factors for coronary artery disease were 13% for overall mortality, 26% for fatal and nonfatal myocardial infarction, and 18% for fatal and nonfatal stroke. Evidence from large trials suggests that patients with type II diabetes compared with patients without diabetes have similar risk reductions from statins for cardiovascular events, but this benefit is not seen in patients with diabetes and end-stage renal disease. In patients with acute coronary syndrome, early treatment with high-dose atorvastatin reduces cardiovascular morbidity after the first 4 months following the event, but the impact on mortality endpoints remains less clear. Results from recent trials in patients with stable coronary artery disease or type II diabetes suggest that statins provide benefit at considerable low LDL cholesterol levels. Therefore, target values for LDL cholesterol of less than 1.8 mmol/l (<70 mg/dl) should be considered for all patients with coronary artery disease or equivalent coronary risk. SUMMARY: For patients at high risk of coronary artery disease there is growing evidence for the concept of 'the lower, the better' regarding LDL cholesterol levels. Ongoing trials are further investigating the safety of lower target values in patients at various risk of coronary artery disease.     

Lipid management after acute coronary syndrome

PURPOSE OF REVIEW: Despite advances in medical therapy and percutaneous revascularization, patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events. Interventions targeting atherogenic lipoproteins may favorably modify this risk. RECENT FINDINGS: Two randomized clinical trials, MIRACL and PROVE-IT, demonstrated efficacy of early, intensive statin therapy after acute coronary syndrome. Recent observational and meta-analyses corroborate the findings of these trials. The benefit of intensive statin treatment appears to apply broadly to elderly as well as younger patients, and to patients with or without diabetes or metabolic syndrome. Randomized trials demonstrating the efficacy of early, intensive statin treatment after acute coronary syndrome employed fixed statin dosages, and there does not appear to be an initial or achieved LDL-cholesterol level below which benefit is absent. As such, broad application of intensive statin therapy after acute coronary syndrome may be preferable to titration of statin dose to achieve specific LDL goals. Low HDL-cholesterol predicts risk after acute coronary syndrome; therefore, pharmacologic interventions to raise HDL concentration or mimic its function may help reduce that risk. SUMMARY: Early, intensive statin therapy is safe and effective after acute coronary syndrome. Future research will determine whether drugs that raise or mimic HDL-cholesterol are effective adjuncts to statin therapy.     

Statin use in acute coronary syndromes: cellular mechanisms and clinical evidence

PURPOSE OF REVIEW: Review the cellular mechanisms and clinical evidence for the use of statins in patients with unstable coronary syndromes. RECENT FINDINGS: Clinical trials of statin therapy in acute coronary syndromes demonstrate a rapid improvement in endothelial function, improved perfusion to ischemic myocardium, and an early reduction in cardiovascular events. The early benefit of statin therapy is related to a combination of molecular mechanisms that involve the oxidized LDL receptor (LOX-1), endothelial localized nitric oxide synthase, inflammatory cytokines, interstitial collagenases, and tissue factor expression. In human atheroma, 3 months' use of statin (pravastatin) therapy reduced the content of oxidized LDL, inflammatory cells (macrophage, T cells) infiltrates, and improved plaque stability by increasing the collagen content of the fibrous cap. SUMMARY: The antiatherothrombotic effects of statin therapy appear to have important clinical relevance to patients with impaired myocardial perfusion and acute coronary syndrome.     

Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.     

Statins – Do we really know all mechanisms of action of this group of drugs?

The role of statins in the treatment and prevention of cardiovascular diseases, such as coronary artery disease, acute coronary syndromes, diabetes or stroke is well established. However, there are still many questions regarding the role of statins in patients with heart failure (HF)/cardiomyopathy (CM), hypertension, atrial fibrillation (AF) and chronic kidney disease (CKD). As for patients with HF/CM inhibition of inflammation, reducing endothelial dysfunction might comprise part of the underlying mechanisms leading to the improvement of left ventricular function and exercise tolerance in these groups of patients. Therefore the candidates for statin therapy with HF/CM should be in New York Heart Association class II or III and should have normal or increased levels of lipids. We should avoid reducing lipids levels in these patients. At present, it is also difficult to unequivocally assess the impact of statins on blood pressure (BP). However, according to most available studies, the impact of statins on the decrease in BP is slight, but significant, especially among patients with hypertension. Moreover statins significantly reduce cardiovascular events in patients with hypertension. Although the results of trials concerning the use of statins in CKD patients are conflicting, it is suggested that the benefits of statin use outweigh the drawbacks in patients with early-stage CKD, when the benefits can be effectively predicted. However, available large randomized clinical trials suggest a lack of efficacy in patients on renal replacement therapy. We also needs further data on the role of statins on AF, however the existing studies suggest beneficial impact of statins in these patients.     

Cardiovascular disease with diabetes or the metabolic syndrome: should statins or fibrates be first line lipid therapy?

PURPOSE OF REVIEW: Subgroups with diabetes or with features of the metabolic syndrome have been increasingly highlighted in large clinical endpoint trials with lipid therapy. This review will focus on the results of trials with statins or fibrates and examine the strength of the evidence for major cardiovascular event reduction with each kind of therapy in these high-risk subgroups that typically have low-to-moderate levels of LDL cholesterol. RECENT FINDINGS: Of six statin trials in populations with moderately increased LDL cholesterol only one, the Heart Protection Study, has shown that statin therapy will significantly reduce the major coronary heart disease events of non-fatal myocardial infarction or coronary heart disease death in diabetes. None of these trials has shown that statins have a particular predilection for reducing cardiovascular events in individuals with higher levels of body weight or other features of the metabolic syndrome. There are far fewer trial data with fibrates than with statins. However, the Veterans Affairs High Density Lipoprotein Intervention Trial has shown that a fibrate can significantly reduce major cardiovascular events, most particularly coronary heart disease death, in those with diabetes as well as those without diabetes who have insulin resistance. Indeed, all fibrate trials show that this therapy appears to selectively benefit the individual with obesity and features of the metabolic syndrome. SUMMARY: Based principally on evidence from the Veterans Affairs High Density Lipoprotein Intervention Trial and the cumulative experience with statins, trial data would thus far suggest that the patient with a modest increase in LDL cholesterol who has diabetes or features of the metabolic syndrome might be likely to achieve more substantial cardiovascular benefit from fibrate than from statin therapy.     

Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis

Background:

Statins were initially used to improve cardiovascular outcomes in people with established coronary artery disease, but recently their use has become more common in people at low cardiovascular risk. We did a systematic review of randomized trials to assess the efficacy and harms of statins in these individuals.

Methods:

We searched MEDLINE and EMBASE (to Jan. 28, 2011), registries of health technology assessments and clinical trials, and reference lists of relevant reviews. We included trials that randomly assigned participants at low cardiovascular risk to receive a statin versus a placebo or no statin. We defined low risk as an observed 10-year risk of less than 20% for cardiovascular-related death or nonfatal myocardial infarction, but we explored other definitions in sensitivity analyses.

Results:

We identified 29 eligible trials involving a total of 80 711 participants. All-cause mortality was significantly lower among patients receiving a statin than among controls (relative risk [RR] 0.90, 95% confidence interval [CI] 0.84–0.97) for trials with a 10-year risk of cardiovascular disease < 20% [primary analysis] and 0.83, 95% CI 0.73–0.94, for trials with 10-year risk < 10% [sensitivity analysis]). Patients in the statin group were also significantly less likely than controls to have nonfatal myocardial infarction (RR 0.64, 95% CI 0.49–0.84) and nonfatal stroke (RR 0.81, 95% CI 0.68–0.96). Neither metaregression nor stratified analyses suggested statistically significant differences in efficacy between high-and low-potency statins, or larger reductions in cholesterol.

Interpretation:

Statins were found to be efficacious in preventing death and cardiovascular morbidity in people at low cardiovascular risk. Reductions in relative risk were similar to those seen in patients with a history of coronary artery disease.Although statins are known to improve survival and relevant clinical outcomes in high-risk populations,¹ evidence of their clinical benefit in lower risk populations is more equivocal. Initially, low-risk populations were defined by the absence of known coronary artery disease (and their treatment was termed “primary prevention”). However, it was subsequently recognized that these populations included both patients at very high risk of coronary artery disease (e.g., those with severe peripheral vascular disease) and those at very low risk (e.g., those aged < 40 years who have no diabetes or hypertension and have low-density lipoprotein cholesterol level of less than 1.8 mmol/L). Accordingly, current guidelines for the use of statins are based on the projected risk of an atherosclerotic event rather than solely on the presence or absence of known coronary artery disease.^2,3Results of the recent JUPITER study (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)⁴ have renewed enthusiasm for the use of statins in people without a history of coronary artery disease and have generated further controversy as to whether high-potency statins such as rosuvastatin and atorvastatin lead to better clinical outcomes than low-potency statins such as pravastatin, simvastatin, fluvastatin and lovastatin. We did a systematic review of randomized trials to assess the efficacy and harms of statins in people at low cardiovascular risk, including indirect comparisons of high-potency and low-potency statins.     

Menopausal Hormone Therapy and Coronary Heart Disease: Reconciling Divergent Findings from Observational Studies and Clinical Trials

Randomized clinical trials of menopausal hormone therapy have shown increased risks of coronary heart disease in the first few years after randomization, and neutral or increased risk over the full trial period. These results diverge substantially from the protective associations of menopausal hormone use with coronary heart disease found in observational studies. In common with many other studies, conventional analyses in the Women’s Health Initiative Observational Study cohort of estrogen plus progestin users showed an association with reduced risk of coronary heart disease even after adjustment for potential confounders. However, upon allowing risk to vary by time since initiation, the hazard ratios did not differ significantly from those observed in the clinical trial. In analyses combining clinical trial and observational data the hazard ratios were 1.58 (1.12, 2.24) within the first 2 years after initiation, 1.19 (0.87, 1.63) between 2 and 5 years, and 0.63 (0.59, 1.26) after 5 years. Similar analyses for estrogen alone also reconciled trial and observational data. These findings were confirmed in novel re-analyses of the Nurses’ Health Study when investigators for the first time included outcomes occurring in the interval between the biennial study cycles. The key towards understanding the underestimation of coronary heart disease in observational studies of menopausal hormone therapy appears to lie in the time-dependent nature of coronary heart disease risk rather than differences in study populations. Observational studies typically do not capture early events in current users and the data mostly reflect the experience of long-term users who have survived the early risk, while clinical trials by design capture early events very efficiently and mainly reflect short-term use.     

Statins in prevention and treatment of ischemic stroke

Based on the published data, including the results of large-scale, randomized, placebo-controlled trials, the article presents current strategies for the use of statins in primary and secondary prevention of ischemic stroke. Special attention is paid to the efficacy and advanced applications of statins in acute stroke. Based on the gross data, recommendations for the use of statins in prevention and treatment of ischemic stroke are presented.     

Women and the management of acute coronary syndrome

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in both men and women in the developed countries. Despite this fact, females are still under-represented in the majority of clinical trials. At the present time, only limited evidence is available with respect to the female-specific aspects of pathogenesis, management, and outcomes in acute coronary syndrome (ACS). Women less frequently undergo coronary intervention, and a lower proportion of women receive evidence-based pharmacotherapy, compared with men. It has been shown that women benefit from an invasive approach and coronary intervention in ACS as much as men, despite their advanced age and higher rate of bleeding complications. Also, administration of beta-blockers, ACE-inhibitors, and intensive statin therapy is associated with a comparable reduction of cardiovascular event rates in women and men. On the other hand, women may profit less than men from fibrinolytic or glycoprotein IIb/IIIa inhibitor therapy. Both sexes benefit equally from aspirin therapy, whereas contradictory data are available on the efficacy of clopidogrel in women. There is an urgent need for intensive research in the development of female-specific therapeutic strategy in ACS, even though the detailed mechanisms of sex differences are still unknown.     

Inflammatory markers and coronary heart disease

PURPOSE OF REVIEW: Despite changes in lifestyle and the use of effective pharmacologic interventions to lower cholesterol levels, coronary heart disease remains the major cause of morbidity and mortality in the developed world. Cholesterol screening fails to identify almost 50% of those individuals who will present with acute coronary syndromes. Recent evidence from laboratory and prospective clinical studies demonstrates that atherosclerosis is not simply a disease of lipid deposition, but rather is an inflammatory process with highly specific cellular and molecular responses. The clinical utility of inflammatory markers has been examined in a variety of atherothrombotic diseases. Because C-reactive protein is highly stable in stored frozen samples, and automated and robust analytical systems for its measurement are available, it has become the most widely examined inflammatory marker. RECENT FINDINGS: C-reactive protein has consistently been shown to be a useful prognostic indicator in acute coronary syndromes and is a strong predictor of future coronary events in apparently healthy individuals. In addition, C-reactive protein can identify individuals with normal lipid levels who are at increased risk for future coronary events. Because drugs such as aspirin and statins reduce inflammatory risk, C-reactive protein has the potential to guide the use of these therapies in high-risk individuals for primary prevention. SUMMARY: C-reactive protein may have a role in global risk assessment for primary prevention and in targeting those patients who will benefit from anti-inflammatory therapies. In addition, it may also be a good prognostic indicator in patients with acute coronary syndromes.     

Evidence-based management of coronary artery disease in the elderly--current perspectives

Cardiovascular disease accounts for significant morbidity and mortality in the elderly. The clinical trial data available to guide therapy in this growing population subset are relatively limited. This review will focus on treatment approaches and recommendations obtained from subgroup analyses of elderly patients from major clinical trials for the management of chronic stable angina, acute coronary syndromes (unstable angina and non-ST-segment elevation myocardial infarction), and coronary revascularization. Recent advances in the treatment of stable angina have shown that use of angiotensin-converting enzyme inhibitors and lipid-lowering therapy as adjunctive measures show benefit in the elderly by reducing the occurrence of death, nonfatal myocardial infarction, and unstable angina. However, if patients experience disabling or unstable anginal symptoms despite effective medical therapy, coronary revascularization must be considered. Several clinical trials have shown a significant reduction in major adverse cardiac events when using intravenous glycoprotein receptor antagonists periprocedurally during percutaneous revascularization approaches in elderly patients with unstable angina or non-ST-segment elevation myocardial infarction, especially when these measures are performed as soon as possible. However, the success of myocardial revascularization by a percutaneous or surgical approach is highly dependent on the patient's associated comorbidities, especially in patients over age 80 years.     

Coronary artery bypass grafting (CABG): reassessing efficacy,safety, and cost

Based on randomized clinical trials begun in the 1970s showing the superiority of coronary artery bypass grafting (CABG) to medical management for patients with coronary artery disease (CAD), CABG has been routinely used to reduce angina and improve chances of survival in patients with CAD. Since CABG became a recognized standard treatment of CAD, considerable evidence has accumulated concerning the pathogenesis of CAD; the efficacy, risks, and costs of CABG; and the effectiveness of CAD risk factor reduction. To re-evaluate efficacy, safety, and cost of CABG, a MEDLINE search was performed to locate randomized trials comparing CABG vs nonsurgical management, CAD pathogenesis studies, and articles evaluating efficacy of coronary artery risk factor reduction behaviors. The extent of revascularization with CABG bore no relationship to relief of angina or survival. Randomized CABG vs medical management studies revealed that only patients with the most advanced CAD had improved survival, and this advantage vanished after 12 years. Researchers kept little coronary risk factor reduction data in the original CABG vs medical management randomized trials. However, in the Bypass Angioplasty Revascularization Intervention (BARI) study, surgically treated patients adopted lifestyles associated with lower coronary risk significantly more than patients treated with angioplasty. Factors other than revascularization cause the improvement in angina associated with CABG. Temporary survival advantages of CAD high-risk subgroups after CABG may be better explained by risk factor reduction rather than by revascularization. Using the BARI data, including lifestyle factors, a multivariate analysis of the influences determining survival and quality-of-life end points would test this hypothesis.     

Statin therapy in heart failure

PURPOSE OF REVIEW: The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors, or statins, have been shown to reduce cardiovascular morbidity and mortality among a wide spectrum of patients with established atherosclerotic vascular disease. Mounting experimental and clinical evidence also suggest a potential benefit as well as theoretical harm of statin therapy in patients with heart failure. RECENT FINDINGS: This article briefly summarizes the therapeutic properties of statins that may be of benefit to patients with heart failure and the theoretical adverse effects of cholesterol reduction in this group of patients. A number of nonrandomized clinical studies over the past several years have shown an association between statin use and reduced overall mortality. Several large-scale randomized studies designed to confirm these findings are currently under way. SUMMARY: Statin therapy appears to improve clinical outcomes in patients with both ischemic and nonischemic cardiomyopathy independently of their cholesterol-lowering properties. The theoretical adverse properties of statins in heart failure patients have not been substantiated in small to medium-sized clinical trials. Although the encouraging results of these preliminary studies suggest a role for statin therapy in heart failure, larger studies are needed to validate these findings. Several ongoing randomized trials are currently under way to evaluate the effect of statin therapy on cardiovascular outcomes in heart failure patients. The results of these studies, expected in the next several years, should provide scientific evidence for the role of statins in the treatment of failure.     

Recommendations from the Consensus Conference on Hypertension in the Elderly.

Since 1978 there have been dramatic advances in the understanding of the pathophysiologic features of unstable angina pectoris and in the availability of new therapies of proven efficacy. Coronary artery spasm has been shown to be an important mechanism of acute myocardial ischemia in patients with unstable angina, and coronary thrombosis has been established as an early event in the development of acute myocardial infarction and, possibly, sudden death. Intravenous nitrates and oral calcium antagonists have been made available and are now widely used. Acetylsalicylic acid has been shown to be of benefit. Improved techniques of myocardial preservation and the introduction of percutaneous transluminal coronary angioplasty have modified the surgical management of coronary artery disease.     

Selenium intake and cardiovascular risk: what is new?

PURPOSE OF REVIEW: Selenium is an essential element with a narrow safety margin. Adequate selenium intake is needed to maximize the activity of glutathione peroxidases and other selenoproteins. This review discusses recent experimental and epidemiologic contributions on the role of selenium for the prevention of atherosclerotic cardiovascular disease. RECENT FINDINGS: Few randomized trials have evaluated the efficacy of selenium supplementation on cardiovascular endpoints. Most trials, conducted in selenium-replete populations, found no evidence of cardiovascular protection. A meta-analysis of 13 prospective cohort studies found a moderate inverse relationship between plasma/serum selenium and coronary heart disease. The interpretation of these data is complicated, however, by potential residual confounding and publication bias. In contrast, recent data from trials of selenium-containing supplements and from epidemiologic studies suggest that chronically increased selenium intake in selenium-replete populations can induce diabetes and maybe also hypercholesterolemia. SUMMARY: Current evidence is insufficient to support a protective role for selenium in cardiovascular prevention. Large high-quality randomized controlled trials and observational studies are needed across populations with different levels of selenium intake. Furthermore, subjects living in regions with high selenium intake should be aware that selenium supplements may increase their risk of diabetes and hypercholesterolemia.     

Effect of statins in stroke prevention

PURPOSE OF REVIEW: This paper reviews recent studies into the outcomes of clinical trials in which statin therapy has been used in the prevention and treatment of strokes. RECENT DEVELOPMENTS: Epidemiologic studies found no or little association between blood cholesterol levels and stroke. Randomized trials have confirmed that LDL lowering decreased the risk of stroke, in diabetic or hypertensive patients with 'normal' LDL cholesterol at baseline, and in patients with coronary artery disease, with respectively 48, 27 and 25% reduction in stroke incidence. A meta-analysis of trials showed that the greater the LDL cholesterol reduction, the greater the intima-media thickness and stroke risk reductions. Even if statins also have 'pleiotropic' effects, their main action seems to be through LDL reduction. The Heart Protection Study only included strokes that occurred 4.6 years before--a time when the stroke event rate is low and the cardiac event rate is high, and so may not have had the power to find a true effect of LDL cholesterol lowering in preventing recurrent stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial may give a definite answer because SPARCL investigators included 4732 patients with brain infarction or transient ischemic attacks and no history of myocardial infarction within 6 months of their stroke event, at a time when the expected stroke rate is very high and the myocardial infarction rate is very low. The results should be announced by mid-2006. SUMMARY: The positive effect of statins on stroke observed in trials of patients with coronary heart disease depended mainly on between-group LDL reduction, but other mechanisms could be involved. Though effective in prevention of major coronary events after a first stroke, statins have not yet been proven effective in prevention of recurrent stroke.     

Statin therapy in the elderly

PURPOSE OF REVIEW: The clinical efficacy and safety of statin therapy have been well established from a series of large-scale, randomized controlled trials. These trials, however, have predominantly recruited patients under the age of 70 years. As a consequence, the use of statins in older patients has remained controversial. RECENT FINDINGS: The results of the first trial to look exclusively at the elderly--the Prospective Study of Pravastatin in the Elderly at Risk--have added enormously to our understanding of the use of statins in the elderly. These findings, together with those from the large elderly cohort within the Heart Protection Study and the smaller elderly subgroups within the other major statin trials, have forced us to re-evaluate any systematic exclusion of elderly patients from statin therapy. SUMMARY: The collective evidence now strongly supports the use of statins in the at-risk elderly population.     

Are statins anti-inflammatory?

Large scale clinical trials demonstrate significant reductions in cardiovascular event rates with statin therapy. The observed benefit of statin therapy, however, may be larger in these trials than that expected on the basis of lipid lowering alone. Emerging evidence from both clinical trials and basic science studies suggest that statins have anti-inflammatory properties, which may additionally lead to clinical efficacy. Measurement of markers of inflammation such as high sensitivity C-reactive protein in addition to lipid parameters may help identify those patients who will benefit most from statin therapy.