Moderate-dose Statin Research Articles

Fenofibric Acid

Fenofibric acid activates peroxisome proliferator-activated receptor alpha to modify fatty acid and lipid metabolism. Fenofibric acid is the first member of the fibric acid derivatives (fibrates) class approved for use as combination therapy with HMG-CoA reductase inhibitors (statins). In three randomized, double-blind, multicenter, phase III trials in adult patients with mixed dyslipidemia, up to 12 weeks' treatment with once-daily fenofibric acid 135 mg plus a low- or moderate-dose statin (atorvastatin 20 or 40 mg, rosuvastatin 10 or 20 mg, or simvastatin 20 or 40 mg) improved high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels to a significantly greater extent than statin monotherapy, and improved low-density lipoprotein cholesterol (LDL-C) levels to a significantly greater extent than fenofibric acid monotherapy. In a 52-week, open-label, multicenter, extension study, HDL-C, TG, and LDL-C levels continued to improve, or were maintained, during combination therapy with once-daily fenofibric acid 135 mg plus a moderate-dose statin (atorvastatin 40 mg, rosuvastatin 20 mg, or simvastatin 40 mg). Once-daily fenofibric acid 135 mg plus a statin was generally as well tolerated as monotherapy with fenofibric acid 135 mg/day or the corresponding statin dosage in the three phase III trials in patients with mixed dyslipidemia. The incidence of adverse events was similar between the combination therapy group and both monotherapy groups. In the extension trial, once-daily fenofibric acid 135 mg plus a moderate-dose statin (atorvastatin 40 mg, rosuvastatin 20 mg, or simvastatin 40 mg) for up to 52 weeks was generally well tolerated.

Effect of Intensive Statin Therapy on Clinical Outcomes Among Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome: PCI-PROVE IT: A PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Substudy

The goal of this analysis was to determine whether intensive statin therapy, compared with moderate-dose statin therapy, leads to a reduction in major adverse cardiovascular events (MACE) among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). When compared with moderate-dose statins, intensive statin therapy reduces MACE among patients with ACS. The role of intensive statin therapy specifically among patients who undergo PCI for ACS is unknown. Outcomes were compared in 2,868 patients who underwent PCI for ACS just prior to enrollment in the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial, which randomized patients to either atorvastatin 80 mg or pravastatin 40 mg daily. The incidence of the primary composite end point of all-cause mortality, myocardial infarction, unstable angina leading to hospitalization, and revascularization after 30 days and stroke was evaluated, as was the incidence of target vessel revascularization (TVR) and non-TVR during follow-up. Treatment with 80 mg atorvastatin reduced the incidence of the composite end point (21.5% vs. 26.5%, hazard ratio: 0.78, 95% confidence interval: 0.67 to 0.91, p=0.002) and lowered the incidence of both TVR (11.4% vs. 15.4%, p=0.001) and non-TVR (8.0% vs. 10.5%, p=0.017) compared with 40 mg pravastatin. After adjusting for on-treatment serum low-density lipoprotein cholesterol and C-reactive protein concentrations, the odds of TVR with high-dose statin therapy remained significant (odds ratio: 0.74, p=0.015) while the odds of non-TVR did not (odds ratio: 0.92, p=0.55). Among patients with ACS who undergo PCI, intensive statin therapy reduces MACE compared with moderate-dose statin therapy. The reduction in the incidence of TVR was independent of low-density lipoprotein cholesterol and C-reactive protein lowering and may therefore be due, at least in part, to a pleiotropic effect of high-dose statin therapy. (PROVE IT-TIMI 22; NCT00382460).

Lipid-Lowering Therapy for the Primary Prevention of Cardiovascular Disease in the Elderly

Although HMG-CoA reductase inhibitors (statins) have been shown to reduce the risk of cardiovascular events in patients aged 65-80 years who have clinical cardiovascular disease, fewer data are available for elderly patients without cardiovascular disease. Treatment guidelines recommend a low-density lipoprotein cholesterol goal of <100 mg/dL for those with cardiovascular disease or diabetes mellitus but vary in their recommendations for primary prevention. Moderate-dose statins have been shown to be effective and safe in properly selected elderly patients up to the age of 80 years. High-dose statins have also been shown to be effective and reasonably safe in patients without significant co-morbidities up to the age of 75 years. With advancing age, the potential for benefit from cholesterol-lowering treatment needs to be weighed against the increasing risk of muscle and hepatic toxicity, as well as competing causes of morbidity and mortality.

Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease

We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20 to 40 mg/day in IDEAL and atorvastatin 10 mg/day in TNT) in patients with clinically evident coronary heart disease or a history of myocardial infarction. The outcome measurement in the present research was CVE occurring after the first year of the trial. After adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p <0.001 for trend across quintiles of TGs). Patients in the highest quintile had a 63% higher rate of CVEs than patients in the lowest quintile (hazard ratio 1.63, 95% confidence interval 1.46 to 1.81) and the relation of TGs to risk was apparent even within the normal range of TGs. The ability of TG measurements to predict risk decreased when high-density lipoprotein cholesterol and apolipoprotein B:apolipoprotein A-1 were included in the statistical analysis, and it was abolished with inclusion of further variables (diabetes, body mass index, glucose, hypertension, and smoking; (p = 0.044 and 0.621, respectively, for trend across quintiles of TGs). Similar results were obtained in patients in whom low-density lipoprotein cholesterol had been lowered to guideline-recommended levels. In conclusion, even slightly increased TG levels are associated with higher risk of recurrence of CVEs in statin-treated patients and should be considered a useful marker of risk.

Long-Term Efficacy of Adding Fenofibric Acid to Moderate-Dose Statin Monotherapy in Patients with Persistent Elevated Triglycerides

Synopsis: NCEP ATP III recommends the addition of a fibrate or niacin to LDL-C lowering treatment to achieve the secondary non-HDL-C goal for patients with triglycerides ≥200 mg/dl who are at their LDL-C goal. Limited long-term efficacy and safety data exist concerning the addition of a fibrate to a statin in patients with mixed dyslipidemia.

Efficacy and safety of fenofibric acid in combination with a statin in patients with mixed dyslipidemia: Pooled analysis of three phase 3, 12-week randomized, controlled studies

Patients with mixed dyslipidemia often require combination therapy to manage multiple lipid abnormalities. To evaluate fenofibric acid in combination with a statin across three studies of patients with mixed dyslipidemia. As prospectively planned, data were pooled from three randomized, double-blind, phase 3 studies of patients with low-density lipoprotein cholesterol (LDL-C) ≥130mg/dL, triglycerides (TG) ≥150mg/dL, and high-density lipoprotein cholesterol (HDL-C) <40mg/dL (men) or <50mg/dL (women). A total of 2715 patients were randomly assigned to 12-week treatment with fenofibric acid 135mg monotherapy; low-, moderate-, or high-dose statin (rosuvastatin, simvastatin, or atorvastatin, depending on study) monotherapy; or fenofibric acid + low- or moderate-dose statin. The primary efficacy comparisons were mean percent change in HDL-C and TG (combination therapy vs. statin) and LDL-C (combination therapy vs. fenofibric acid). Fenofibric acid + low-dose statin increased HDL-C (18.1% vs. 7.4%) and reduced TG (-43.9% vs. -16.8%) versus low-dose statin monotherapy and reduced LDL-C (-33.1% vs. -5.1%) versus fenofibric acid monotherapy (P <.001 for all). Fenofibric acid + moderate-dose statin increased HDL-C (17.5% vs. 8.7%) and reduced TG (-42.0% vs. -23.7%) versus moderate-dose statin monotherapy and reduced LDL-C (-34.6% vs. -5.1%) versus fenofibric acid monotherapy (P <.001 for all). Combination therapy was generally well tolerated, and safety profiles were similar to monotherapies. No rhabdomyolysis was reported. In patients with mixed dyslipidemia, combination therapy simultaneously improved multiple lipid abnormalities more effectively than fenofibric acid or statin monotherapies.

Add-on therapy for hypercholesterolemia: a pilot comparison of two gastrointestinally-acting agents in statin-treated patients

Both colesevelam hydrochloride (colesevelam) and ezetimibe monotherapy have been reported to lower low-density lipoprotein cholesterol (LDL-C) approximately 15-17% in patients with hypercholesterolemia. When statin therapy is inadequate to reach desired LDL-C goals, the choice of add-on therapy, while multifactorial, must consider efficacy of additional LDL-C reduction. To provide pilot study data in assessing the relative potential of ezetimibe or colesevelam to further reduce LDL-C in statin-treated patients. Fourteen patients with hypercholesterolemia, who at baseline were on treatment with a stable regimen of low- to moderate-dose statin therapy, were randomized to receive colesevelam HCl 3.75 g/day or ezetimibe 10 mg/day as add-on therapy (AOT). At the end of 6 weeks, each patient was crossed over to the alternative AOT. LDL cholesterol fell an additional 21.0% on colesevelam (P < .001) and 28.3% on ezetimibe (P <.001) with a 7.3% difference between AOTs (P <.02). Non-high-density lipoprotein cholesterol (non-HDL-C) fell an additional 15.1% on colesevelam (P <.001) and 25.6% on ezetimibe (P <.001) with a 10.5% difference between AOTs (P <.001). The non-HDL-C/HDL-C ratio fell an additional 15.3% on colesevelam (P <.01) and 22.8% on ezetimibe (P <.001) with a 7.5% difference between AOTs (P <.02). Zero of 10 and six of 10 secondary prevention patients reached an LDL-C level of <70 mg/dl on colesevelam and ezetimibe respectively (P <.005). Colesevelam HCl and ezetimibe are both effective AOTs in patients on statin therapy. The superior further improvement in the lipid panel with ezetimibe compared to colesevelam was demonstrated in this placebo uncorrected crossover pilot study.

Is a statin as part of a polypill the answer?

Statins are a necessary component of a polypill. Almost all patients have the potential to benefit from low-density lipoprotein cholesterol reduction with statins, although absolute benefits due to the reduction in coronary heart disease and stroke vary by risk level. The reduction in coronary heart disease and stroke from antihypertensive therapy is additive to the reduction in risk from statins. Used in combination with antihypertensive therapy, a moderate-dose statin would be expected to reduce cardiovascular risk by at least 50%, and a high-dose statin would be expected to reduce risk by at least 60% over an approximately 5-year period. A polypill containing aspirin in addition to a statin and antihypertensive therapy would be appropriate for most men over age 55 years, but not for high-risk women until age 65 years and moderately high-risk women until age 75 years. Polypills in development hold great promise for reducing the global burden of cardiovascular disease.

Long-term safety and efficacy of fenofibric acid in combination with statin therapy for the treatment of patients with mixed dyslipidemia

Co-administration of a fibrate and statin is an effective treatment option for patients with multiple lipid abnormalities, yet adequate long-term safety and efficacy data are lacking. To evaluate the long-term safety and efficacy of fenofibric acid combined with statins in adults with mixed dyslipidemia. Three large, 12-week, phase three, double-blind, randomized, controlled trials evaluated fenofibric acid 135 mg combined with a low- or moderate-dose statin compared to fenofibric acid or statin monotherapy, and a subsequent 52-week open-label extension study evaluated fenofibric acid 135 mg combined with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg). This prespecified analysis integrated results from these studies to assess the long-term safety and efficacy of combination therapy. Across the controlled studies and the extension study, 2201 patients received at least one dose of fenofibric acid + statin for a median duration of 364 days. The most common adverse events were headache, upper respiratory tract infection, nasopharyngitis, and back pain, with the incidence of all adverse events being similar across all combination therapy treatment groups. Rhabdomyolysis or treatment-related death was not reported in any group. Combination therapy resulted in sustained improvements in multiple lipid parameters, including triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Long-term fenofibric acid + statin combination therapy was generally well tolerated and resulted in comprehensive and sustained improvements in multiple lipid parameters in adults with mixed dyslipidemia.

LDL reduction: How low should we go and is it safe?

High-dose statin therapy or combination statin treatment is necessary for most patients to achieve aggressive low-density lipoprotein cholesterol goals. Adding ezetimibe or bile acid sequestrants appears unlikely to increase the risk of myopathy. Although the combination of niacin or fenofibrate with moderate-dose statins appears to be reasonably safe, the safety of combination with high-dose statins has yet to be determined. To enhance patient outcomes, attention must be paid to characteristics that predict muscle and hepatic statin toxicity when considering using high-dose statin or combination statin therapy.

Abstract 3732: Long-Term Safety and Efficacy of ABT-335 (Fenofibric Acid) in Combination with Statin Therapy for the Treatment of Patients with Mixed Dyslipidemia

Background: The efficacy and safety of ABT-335 + statin combination therapy was demonstrated in three 12-week, controlled studies of patients with mixed dyslipidemia randomized to ABT-335 (135mg) + low or moderate dose rosuvastatin (R), simvastatin (S), or atorvastatin (A), or ABT-335 or statin monotherapy. A subsequent 52-week open label extension study evaluated the long-term safety and efficacy of ABT-335 combined with statins. Methods: Patients who completed 12 weeks of treatment in the 3 controlled studies were eligible to enroll in the 52-week extension study to receive ABT-335 + the moderate dose statin that was used in their initial study: R 20mg, S 40mg, or A 40mg. This was a pre-specified, integrated analysis of patients receiving ABT-335 + statin in the 12- and 52-week studies. Results: Of the 2715 randomized patients, 2316 completed the 12-week studies and 1911 enrolled in the extension study. A total of 2201 patients received at least 1 dose of ABT-335 + statin for a median duration of 364 days; 1139 patients were treated for ≥52 weeks. The incidence of adverse events (AEs) was similar across all 3 combination therapy groups (Table ). The most common AEs were headache, upper respiratory tract infection, nasopharyngitis, and back pain. Rhabdomyolysis was not reported in any group. Patients who were initially randomized to ABT-335 + statin and continued in the extension study (N=979) had sustained improvements in multiple lipids. After 12 and 52 weeks of treatment, combination therapy resulted in mean percent decreases in TG (−45.7% and −47.5%, respectively) and LDL-C (−32.2% and −37.8%), and increases in HDL-C (17.6% and 23.8%). Mean values at 12 and 52 weeks were: TG 141.2 and 136.3 mg/dL; LDL-C 101.6 and 93.5 mg/dL; and HDL-C 45.0 and 47.1 mg/dL, respectively. Conclusions: Long-term ABT-335 + statin combination therapy was generally well tolerated and resulted in comprehensive and sustained improvements in TG, HDL-C, and LDL-C in adults with mixed dyslipidemia. Summary of safety, n/N (%)

Influenza and COPD Mortality Protection as Pleiotropic, Dose-Dependent Effects of Statins

Published data on antiinflammatory and immunomodulatory effects of statins suggest they may reduce mortality risks associated with an unchecked immune response to selected infections, including influenza and COPD. We assessed whether statin users had reduced mortality risks from these conditions. We conducted a matched cohort study (n = 76,232) and two separate case-control studies (397 influenza and 207 COPD deaths) to evaluate whether statin therapy is associated with increased or decreased mortality risk and survival time using health-care encounter data for members of health maintenance organizations. For the cohort study, baseline illness risks from all causes prior to initiation of statin therapy were used to statistically adjust for the occurrence of outcomes after initiation of treatment. For moderate-dose (>/= 4 mg/d) statin users, this cohort study found statistically significant reduced odds ratios (ORs) of influenza/pneumonia death (OR, 0.60; 95% confidence interval [CI], 0.44 to 0.81) and COPD death (OR, 0.17; 95% CI, 0.07 to 0.42) and similarly reduced survival hazard ratios. Findings were confirmed with the case-control studies. Confounding factors not considered may explain some of the effects observed. This study found a dramatically reduced risk of COPD death and a significantly reduced risks of influenza death among moderate-dose statin users.

Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy

Background: Randomized trials evaluating intensive dose statin therapy have found enhanced protection against cardiovascular (CV) events compared with moderate-dose statin therapy in patients with acute coronary syndromes (ACS) or stable coronary artery disease (CAD). However, the potential for an increase in the risk of drug-induced adverse events with such therapy has not been quantified. Objective: This meta-analysis was performed to compare the incremental risks associated with intensive- and moderate-dose statin therapy. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1995 to 2006 using the following terms: acute, coronary syndrome, stable coronary artery disease, atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, and fluvastatin. Prospective, randomized controlled trials evaluating intensive- and moderate-dose statin therapy for the reduction of CV events were included in the review. The safety end points examined were elevations in creatine kinase (CK) ≥ 10 times the upper limit of normal (ULN), elevations in alanine or aspartate aminotransferase ≥3 times the ULN, rhabdornyolysis, drug-induced adverse events requiring discontinuation of therapy, and any drug-induced events. The efficacy end points examined were all-cause mortality, CV death, nonfatal myocardial infarction (MI), and stroke. Each analysis compared the effect of intensive- or moderate-dose statin therapy on statin-induced adverse events and clinical efficacy outcomes. Simple absolute risk, the number needed to treat, and the number needed to harrrn were also calculated to quantify the incremental benefit or harm associated with intensive-dose statin therapy. Results: Four trials were included in the analysis.Together, they included 27,548 patients with ACS or stable CAD followed for a mean of 3.4 years, representing 108,049 patient-years of clinical-trial experience. Intensive-dose therapy with atorvastatin or simvastatin 80 mg was associated with a significant increase in the risk for any adverse event (odds ratio [OR] = 1.44; 95% CI, 1.33–1.55; P < 0.001) and adverse events requiring discontinuation of therapy (OR = 1.28; 95% CI, 1.18–1.39; P < 0.001). Intensive-dose therapy also was associated with an increased risk for abnormalities on liver function testing (OR = 4.48; 95% Cl, 3.27–6.16; P < 0.001) and elevations in CK (OR = 9.97; 95% CI, 1.28–77.92; P = 0.028). The benefits of intensive-dose statin therapy included reductions in CV death (OR = 0.86; 95% CI, 0.75–0.99; P = 0.031), MI (OR = 0.84; 95% CI, 0.76–0.93; P < 0.001), and stroke (OR = 0.82; 95% CI, 0.72–0.94; P = 0.004). Conclusions: Although intensive-dose statin therapywas associated with a reduced risk for important CV events, it was also associated with an increased risk for statin-induced adverse events. Therefore, moderate-dose statin therapy may be the most appropriate choice for achieving CV risk reduction in the majority of individuals, whereas intensive-dose statin therapy may be reserved for those at highest risk.

Is it Time for a Cardiovascular Primary Prevention Trial in the Elderly?

Statins have been shown conclusively to reduce the risk of cardiovascular events in subjects with clinical cardiovascular disease or diabetes aged 65 to 80 years of age. However, few data are available for primary prevention of cardiovascular disease in those aged > or =70 years. A moderate-dose statin was of little benefit in a population aged 70 to 82 years when given for 3 years in the setting of suboptimally treated blood pressure. More evidence supports the use of blood pressure-lowering medications, but few data are available regarding the appropriate blood pressure target and most effective agents in the elderly. Some evidence also suggests that the elderly could experience higher mortality with antihypertensive treatment. These findings, along with greater safety concerns and an increasing number of competing risks and medical conditions with advancing age, make it imperative to carefully evaluate the risk/benefit balance from treating hypercholesterolemia and hypertension in persons aged > or =70 years. We propose a 5-year 2x2 factorial trial of primary prevention in the elderly that will (1) evaluate whether statin therapy will reduce the risk of cardiovascular events when added to the treatment of hypertension to achieve a blood pressure <140/90 mm Hg in most patients and (2) determine the most appropriate blood pressure regimen for the prevention of cardiovascular and renal events.

Cost-effectiveness of high-dose atorvastatin compared with usual-dose simvastatin: less than IDEAL?

The use of statins in the management and prevention of coronary artery disease has been shown to be associated with significant reductions in the incidence of major adverse events, including death, myocardial infarction (MI), and stroke.1 Clinical practice reflects the impact of this evidence: between the EUROASPIRE I and II surveys, reported rates of statin use in Europe increased from 18.5% in 1995–96 to 57.7% in 1999–2000 among patients with coronary heart disease.2 Despite this increase, over 40% of the patients had failed to reach targeted cholesterol concentrations. Four recent trials have examined the impact of higher dose statins compared with standard dose statins in meeting more stringent low-density lipoprotein (LDL) cholesterol goals and thereby reducing cardiovascular outcomes.3 The most recent of these, the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) trial, randomized 8888 patients with a history of acute MI (AMI) to either 80 mg/day atorvastatin (the high dose treatment) or 20 mg/day simvastatin (the moderate dose treatment).4 The high dose treatment was not associated with a significant decrease in the primary outcome of a major coronary event (including death, confirmed non-fatal AMI, or cardiac arrest with resuscitation) but was associated with a reduction in secondary endpoints and non-fatal AMI. In this article, Lindgren et al . present the results of a cost-effectiveness analysis of the IDEAL study.5 This study is important for several reasons: it is the first published economic evaluation of high-dose vs. moderate-dose statin therapy; and the first study to be conducted after the introduction of generic simvastatin. The incremental cost per quality adjusted life year … Corresponding author. Tel: +1 780 407 8680; fax: +1 780 407 8368. E-mail address : pkaul{at}ualberta.ca

Managing Cholesterol in the Elderly

Statins have been shown conclusively to reduce the risk of cardiovascular events in patients aged 65–80 years with clinical cardiovascular disease. Less evidence is available for elderly patients with diabetes but without cardiovascular disease and for primary prevention with advancing age. Treatment guidelines recommend a low-density lipoprotein cholesterol goal of less than 100 mg/dl for those with cardiovascular disease or diabetes, but vary in their recommendations for primary prevention. Moderate-dose statins have been shown to be safe and effective in properly selected elderly patients. High-dose statins have also been demonstrated to be effective and reasonably safe in patients without significant comorbidities up to the age of 75. With advancing age, the potential for benefit from cholesterol treatment must be weighed against the increasing risk of muscle and hepatic toxicity.

Low-density lipoprotein cholesterol lowering in the prevention of CHD: How low should we go?

The past 12 years have seen the publication of numerous randomized placebo-controlled studies using statins to lower low-density lipoprotein cholesterol (LDLC) to assess the efficacy of cholesterol lowering on cardiovascular events. Initial studies predominantly evaluated mortality or nonfatal myocardial infarctions and coronary heart disease (CHD) death in patients with known or presumed established coronary disease and moderately elevated to very elevated serum cholesterol concentrations. Subsequent investigations studied a broader spectrum of cardiovascular events as a composite primary end point in both primary and secondary prevention strategies in subjects with lower mean entry serum LDLC concentrations. These studies have generally shown a reduction in a composite end point of cardiovascular events, although not necessarily the more restricted end points used in previous studies. Although the LDLC mantra "lower is better" has been popularized in advertising and continuing medical education and suggested as an option in "very high risk" patients by the National Cholesterol Education Program Adult Treatment Panel, the precise target level for LDLC for optimal treatment has not been rigorously defined. Serum LDLC less than 100 mg/dL seems reasonable for patients with known atherosclerosis or at high risk for atherosclerosis (diabetes or presence of multiple risk factors). Serum LDLC less than 70 mg/dL may be a reasonable goal in the setting of acute coronary syndromes, but there are many problems with the data on which this recommendation is made. Furthermore, many advocates of "lower is better" seem oblivious to the potential downsides of more aggressive lipid-lowering therapy. The LDLC target in lower risk primary prevention is less clear. What is obvious is that moderate-dose statin therapy can lower CHD risk in primary prevention and secondary prevention with minimal side effects, and with the imminent availability of several generic statins, with great cost-effectiveness.

Issue Highlights

HomeCirculationVol. 113, No. 11Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published21 Mar 2006https://doi.org/10.1161/circ.113.11.1377Circulation. 2006;113:1377EPINEPHRINE QT STRESS TESTING IN THE EVALUATION OF CONGENITAL LONG-QT SYNDROME: DIAGNOSTIC ACCURACY OF THE PARADOXICAL QT RESPONSE, by Vyas et al.The diagnosis of congenital long-QT syndrome (LQTS) may not be entirely clear from a resting ECG. With exercise or catecholaminergic provocation, most healthy individuals have QT interval shortening, whereas patients with type 1 LQTS (LQT1; due to KCNQ1 mutations) may have QT prolongation. In this issue of Circulation, Vyas and colleagues sought to validate the diagnostic accuracy of an epinephrine infusion for paradoxical QT prolongation in LQT1 patients. They studied 125 genotyped untreated patients (40 LQT1, 30 LQT2, 11 LQT3, and 44 genotype-negative) and observed QT shortening with epinephrine provocation in most genotype-negative and LQT3 patients, but QT lengthening in 92% of LQT1 patients (compared with 18% of genotype-negative and 13% of LQT2 patients). The authors conclude that a paradoxical QT prolongation 30 ms in response to epinephrine challenge has a positive predictive value of 76% and negative predictive value of 96% for LQT1. The test characteristics were much poorer if patients were already on β-blocker therapy. This safe, relatively simple test may be of particular value in diagnosing patients with indeterminate LQTS and may unmask “concealed LQTS.” See p 1385.A TALE OF TWO TRIALS: A COMPARISON OF THE POST–ACUTE CORONARY SYNDROME LIPID-LOWERING TRIALS A TO Z AND PROVE IT-TIMI 22, by Wiviott et al.Several trials have reported comparisons of intensive- versus moderate-dose statin therapy in patients who present with an acute coronary syndrome. Although the bulk of the evidence has fallen in favor of early intensive-dose statin therapy, the magnitude of the treatment benefit has varied from trial to trial. To help clinicians through the complex datasets of the Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trials, Wiviott et al analyze the demographics, end point definitions, impact on low-density lipoprotein (LDL), and impact of C-reactive protein (CRP) in those two studies. Potential implications from their analysis include the benefit of early intensive therapy when combined with revascularization. The relationship of reductions in CRP to early benefit provides further support for the antiinflammatory events of statins. This type of synthesis across trials is a welcome addition to the cardiovascular literature and helps focus therapeutic decision making for clinicians. See p 1406.SAFETY OF CORONARY SIROLIMUS-ELUTING STENTS IN DAILY CLINICAL PRACTICE: ONE-YEAR FOLLOW-UP OF THE E-CYPHER REGISTRY, by Urban et al.Over the past several years, drug-eluting stents have become widely utilized in coronary interventional procedures as the revascularization modality of choice. Increased use of these stents, in turn, has markedly reduced restenosis rates as compared to rates seen with bare metal stents, resulting in a decrease in target vessel revascularization rates. A number of randomized clinical trials now have clinical and angiographic follow-up demonstrating the long-term durability of these stents. Interestingly, although these landmark trials studied only highly select patient populations with prespecified lesion characteristics, it remained unknown if these findings would extend to a heterogeneous patient population with higher-risk coronary artery lesions. In this issue of Circulation, Urban et al present data from the e-Cypher registry that examine the safety and efficacy of sirolimus-eluting stents in daily practice. See p 1434.Visit http://circ.ahajournals.org:Clinician UpdateCardiovascular Genomics. See p e450.Images in Cardiovascular MedicineA Left Atrial Appendage Thrombus Mimicking Atrial Myxoma. See p e456.Hereditary Hypertrophic Nonobstructive Cardiomyopathy Seen on Delayed Hyperenhancement Magnetic Resonance Imaging. See p e458. Download figureDownload PowerPointTime-Resolved 3-Dimensional Magnetic Resonance Velocity Mapping at 3 T Reveals Drastic Changes in Flow Patterns in a Partially Thrombosed Aortic Arch. See p e460.CorrespondenceSee p e462. Previous Back to top Next FiguresReferencesRelatedDetails March 21, 2006Vol 113, Issue 11 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.113.11.1377 Originally publishedMarch 21, 2006 PDF download Advertisement