Interview with Dr. Paul Thompson on the Role of Coenzyme Q10 (CoQ10) in Statin-Associated Myopathy

Paul D. Thompson, MD

Although serious statin-associated myopathy is rare, muscle-related complaints are generally held to be the most common and clinically significant adverse effects of statin therapy. The mechanism by which statins may affect muscle is unknown, and a number of explanations have been proposed. One theory that has attracted wide interest relates statin-associated muscle complaints to depletion of coenzyme Q10 (CoQ10). The role of CoQ10 in statin-associated myopathy is the subject of a recently published systematic review by Leo Marcoff and APOLLO Steering Committee member Paul D. Thompson.¹ In this interview, Dr. Thompson discusses the prevalence of statin-related muscle complaints, theories about their causation, and the conclusions of his and Dr. Marcoff’s review of the evidence on the role of CoQ10.

Interview with Dr. Michael Davidson on the Safety of Lipid-Modifying Therapy

Michael H. Davidson, MD, FACC, FACP

The National Lipid Association has issued 2 reports on the safety of lipid-modifying drug therapy: the Report of the National Lipid Association’s Statin Safety Task Force, published in April 2006,¹ was followed recently, in March 2007, by the Report of the National Lipid Association’s Safety Task Force: the Nonstatins.² In this interview, APOLLO Steering Committee member Dr. Michael H. Davidson, a participant in both NLA task forces, reviews the evidence regarding the safety of lipid-modifying therapy—including standard and intensive statin therapy, nonstatin agents, and combination therapy—and what it means for clinicians and their patients.

Interview with Dr. Peter Tóth: Bad News/Good News: the Latest on HDL

Peter P. Tóth, MD, PhD, FAAFP, FAHA, FACC

Among the notable clinical trials whose results were presented at the recent 56th Scientific Session of the American College of Cardiology (held March 24-27, 2007, in New Orleans), 2 trials of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib were of particular interest to lipidologists and preventive cardiologists. In the Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation (ILLUSTRATE) and the Rating Atherosclerotic Disease Change by Imaging With a New CETP Inhibitor (RADIANCE 1) trial, torcetrapib demonstrated a remarkable ability to raise high-density lipoprotein cholesterol (HDL-C) levels yet failed to produce the anticipated beneficial effect on clinical efficacy end points. HDL and its potential role in preventive therapy were evaluated in another trial presented at the ACC meeting, Effect of Reconstituted High-Density Lipoprotein on Atherosclerosis: Safety and Efficacy (ERASE). In this editorial–interview, APOLLO Steering Committee member Dr. Peter P. Tóth discusses the background and results of these trials and their implications for the present and future role of HDL-related therapies in the management of cardiovascular disease (CVD) and CVD risk.

Interview with Dr. Douglas Thompson on The National Growth and Health Study

Douglas Thompson, PhD*

In 1985, the National Growth and Health Study (NGHS), sponsored by the National Heart, Lung, and Blood Institute (NHLBI), was undertaken to examine racial differences in the development of obesity in pubescent girls and identify possible psychosocial, socioeconomic, and environmental correlates of those differences.1 The study was also designed to examine correlations between the development of overweight and obesity during childhood and cardiovascular disease risk factors such as blood pressure and serum lipids. The study included 1166 white and 1213 black girls aged 9 or 10 years who were followed up annually to the age of 18 years, with additional information obtained through telephone interviews at ages 21 to 23 years. Data from the NGHS have been analyzed in a number of reports, of which the most recent, examining the correlation between childhood overweight and cardiovascular risk factors, was published in February 2007 in The Journal of Pediatrics.2 APOLLO interviewed Douglas R. Thompson, PhD, of the Maryland Medical Research Institute, the lead author of that report.

Interview with Dr. Daniel Rader on FH

Daniel J. Rader, MD*

The study of homozygous familial hypercholesterolemia (FH), which is quite rare, has given researchers insight into the association between high cholesterol levels and risk for cardiovascular disease. At present, treatment options for this disorder are limited in range and efficacy. A recent study involving use of a microsomal triglyceride transfer protein (MTP) inhibitor provides a potentially new direction for approaching treatment of FH. APOLLO interviewed one of the study’s coauthors, Dr. Daniel J. Rader of the University of Pennsylvania School of Medicine in Philadelphia, and discussed with him the implications of this study both for future treatment options for patients with FH and for other patients with hypercholesterolemia.

Interview with Dr. Allen Taylor on the FAME study

Allen J. Taylor, MD, FACC, FAHA*

It is well known that rates of nonadherence to prescribed drug therapy are high, with the result that for many patients, the full benefit of treatment is not realized. However, although the problem is recognized, we have not had strategies of proven effectiveness to reduce nonadherence. The first major cardiovascular clinical study testing the effectiveness of a program to promote medication compliance was recently concluded. The results of the Federal Study of Adherence to Medications in the Elderly (FAME) were presented on November 14, 2006, at the American Heart Association 2006 Scientific Sessions and simultaneously published online by JAMA.

Interview with Dr. Michael Davidson on the CHICAGO Trial

Michael H. Davidson, MD, FACC, FACP

In a late-breaking clinical trials session of the 2006 American Heart Association Scientific Sessions, researchers presented results of the Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone (CHICAGO) study. In a multiethnic, multiracial population of patients with type 2 diabetes (N = 462), the CHICAGO study compared 2 oral antidiabetic agents, the thiazolidinedione pioglitazone and the sulfonylurea glimepiride, to determine whether the thiazolidinedione had a beneficial cardiovascular effect independent of its antiglycemic effect. The primary end point was change in carotid intima-media thickness as a surrogate for progression of atherosclerosis.

Interview with Pierre Amarenco, MD on the SPARCL Trial

Pierre Amarenco, MD

In cardiovascular clinical trials, treatment with statins has consistently been shown to reduce the risk for stroke. However, since statin trials have rarely included substantial numbers of patients with a history of stroke, this evidence supports the effectiveness of statins for primary but not for secondary stroke prevention. The recently concluded Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was the first clinical study designed to evaluate the efficacy and safety of statin therapy in the secondary prevention of stroke during the early poststroke period, when the risk for recurrence is highest.

Is the FDA's Adverse Event Reporting System Broken?

Some Say It Is, but It Is Still an Essential Step in Identifying Important Adverse Events Associated With the Drugs We Prescribe

James M. McKenney, PharmD

In spite of the criticism, deserved or undeserved, that it attracts, the FDA's Adverse Event Reporting System (AERS) serves a vital purpose. The type of data that the AERS collects is essential for the identification of rare adverse drug effects. These rare adverse effects can be serious and may easily escape detection in clinical trials because they occur in fewer than 0.1% of people taking a drug. All prescribers should know how the system works and what its data mean.

Interview with Dr. Gregg Fonarow on the new AHA/ACC Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease

Gregg C. Fonarow, MD, FACC, FACP

The American Heart Association (AHA) and the American College of Cardiology (ACC) recently issued an updated revision of their guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease. The last version of the guidelines was published in 2001. The 2006 update is notable as the first set of approved guidelines that takes account of the large body of evidence that has accrued from the major cardiovascular clinical trials of the last several years.

Interview with Keith Ferdinand, MD, FACC on the ARIES, IRIS and STARSHIP trials
Keith Ferdinand, MD, FACC

At the XIV International Symposium on Atherosclerosis (ISA), held June 18-22 in Rome, results were presented from 3 North American clinical trials, ARIES, IRIS, and STARSHIP, which compared rosuvastatin and atrovastatin therapy in, respectively, African American, South Asian, and Hispanic patients. These were the first large comparative drug trials to evaluate the efficacy and safety of statins in specific minority racial and ethnic patient populations.

Interview With Steven Nissen, MD on the ASTEROID Trial
Steven Nissen, MD

The results of the ASTEROID trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound–Derived Coronary Atheroma Burden) were published in JAMA (April 5, 2006). The prospective, open-label blinded end-points trial used intravascular ultrasound (IVUS) to assess the progression or regression of atherosclerosis in receiving intensive statin therapy.

Interview with Dr. Christie Ballantyne on Metabolic Syndrome
Christie M. Ballantyne, MD

Metabolic syndrome is a cluster of clinical and biochemical abnormalities associated with the onset and progression of atherosclerotic cardiovascular disease (CVD). Adults with metabolic syndrome experience significantly greater mortality from coronary artery disease (CAD), vascular disease, stroke, and other causes in comparison with those who do not have the disorder.

Interview with Dr. Christopher Cannon on the IDEAL Study
Christopher Cannon, MD

The results of the Incremental Decrease in Endpoints Through Aggressive Lipid Lowering (IDEAL) study were reported at the American Heart Association’s Scientific Sessions 2005 and published simultaneously in JAMA (November 16, 2005).¹ The study compared intensive and standard lipid-lowering therapy (atorvastatin 80 mg/d vs simvastatin 20 mg/d) in patients with previous myocardial infarction (MI). The reduction of risk for the composite primary end point, major coronary events, in the intensively treated group was not statistically significant.

Repercussions: Health Care After Hurricane Katrina
Keith C. Ferdinand, MD, FACC

Socioeconomic and racial/ethnic disparities in the quality and availability of health care persist in the United States, and this has been particularly evident in New Orleans and other communities of the Gulf Coast region, including Mississippi and Alabama.

Interview with Dr. Antonio Gotto at AHA: Implications of FIELD
Antonio M. Gotto, Jr., MD, DPhil

The results of the landmark Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were presented November 14 at the American Heart Association’s Scientific Sessions 2005. Patients with type 2 diabetes mellitus are at increased risk for cardiovascular disease, partly owing to diabetic dyslipidemia, which can be responsive to fibrate therapy.

How Low Can You Go . . . Safely?
Stephen D. Wiviott, MD

The benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been observed in major primary^2-4 and secondary^3-7 prevention trials across a wide range of cholesterol levels in stable patients.

Interview with Dr. Michael Davidson at EASD: Implications of PROactive
Michael H. Davidson, MD, FACC, FACP
Athens, Greece. The results from the landmark Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) were presented at the 41st meeting of the European Association for the Study of Diabetes (EASD) 2005.

Hyperlipidemia and HIV

Alison D. Schecter, MD

HIV-AIDS is a devastating disease responsible for more than 100,000 deaths in the United States alone between 1987 and 1999.¹

Implications of ASCOT and CARDS
Christie M. Ballantyne, MD
Clinical trial evidence has established the benefit of lipid-regulating statin therapy in patients with elevated low-density lipoprotein cholesterol (LDL-C), but in a growing number of patients, cardiovascular risk is increased by the presence of the metabolic syndrome, characterized by elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C), hypertension, and insulin resistance.

Aspirin in the Primary Prevention of Cardiovascular Disease Among Women

Paul M. Ridker, MD
Julie E. Buring, ScD

Oral aspirin in dosages ranging from 75 through 325 mg/d is a proven therapy in the treatment of high-risk unstable angina and acute myocardial infarction (MI), as well as in the secondary prevention of both coronary and cerebral thrombosis.

TNT ADDS TO THE PERSPECTIVE: LOWER IS BETTER
James M. McKenney, PharmD

The much-anticipated Treating to New Targets (TNT)¹ study is the third of 5 studies that seek to answer the question, Compared with less aggressive low-density lipoprotein cholesterol (LDL-C) lowering to current treatment goals, does more aggressive LDL-C lowering provide a significant differential coronary artery disease (CAD) risk reduction?

HYPERCHOLESTEROLEMIA IN AFRICAN AMERICAN PATIENTS
Keith C. Ferdinand, MD, FACC

African Americans, when compared to the general population and other racial/ethnic minorities in the United States, have the highest overall rate of coronary heart disease mortality, sudden cardiac death, and incidence of several comorbid conditions. Particularly, there is a greater prevalence of type 2 diabetes and multiple coronary heart disease risk factors, including hypertension, renal insufficiency, and obesity, especially in African American females...

STATINS AND HDL-C
Peter P. Toth, MD, PhD, FAAFP, FACC

High-density lipoproteins (HDLs) mediate a broad variety of antiatherogenic effects within the cardiovascular system. The most important antiatherogenic function of HDLs is believed to be its ability to drive reverse cholesterol transport, a process by which HDLs are able to translocate excess cholesterol mass from cells within the subendothelial space and atheromatous plaque and deliver it back to the liver for elimination via the gastrointestinal tract...

Going Beyond LDL: ApoA-1 Milano, HDL, and Triglycerides
Antonio M. Gotto, Jr., MD, DPhil

The benefits of aggressive, long-term lipid management to reduce coronary and cardiovascular risk are well established. Despite the evidence of benefit, however, cholesterol management remains underimplemented, even in the patients at highest risk for cardiovascular events...