Researchers Weigh In on Applicability of New Cholesterol Guidelines in Subpopulations

Despite the release of new cholesterol guidelines this week, questions remain as to how much evidence really exists in certain subpopulations. Several coauthors of the new guidelines discussed the evidence supporting cholesterol lowering in women, the elderly, and minorities during a session entitled “Clinical Lipidology: Controversies in Cardiovascular Risk Reduction.” The American College of Cardiology (ACC) and American Heart Association (AHA) guidelines base treatment on a 10-year risk for atherosclerotic cardiovascular disease (ASCVD),¹ a shift from the previous guidelines’ overall emphasis on “treat to target.” The new guidelines recommend treatment with statins for 4 “statin benefit groups”¹:

1. Individuals with clinical ASCVD
2. Individuals with primary elevations of low-density lipoprotein cholesterol (LDL-C) greater than or equal to 190 mg/dL
3. Individuals 40 to 75 years of age with diabetes with LDL-C 70 mg/dL to 189 mg/dL
4. Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL-C between 70 mg/dL and 189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher

For years, women were vastly underrepresented in clinical studies in heart disease, said C. Noel Bairey Mertz, MD, FACC, director, Barbra Streisand Women’s Heart Center, director, Preventive and Rehabilitative Cardiac Center, Women’s Guild chair in women’s health, and professor of medicine, Cedars-Sinai Heart Institute. Dr Mertz discussed the evidence for use of statin therapy in primary prevention. Despite the fact that larger numbers of women than men have cardiovascular disease (CVD), the majority of clinical trials historically enrolled mostly white middle-aged men. Most of what is learned is garnered through subgroup analyses, which is inherently based on small sample sizes, lower precision, and wide confidence intervals. Dr Mertz also referred several times to the criticisms of Rita F. Redberg, professor and director, women’s cardiovascular services, professor of medicine, University of California, San Francisco, who co-wrote an op-ed piece in The New York Times² that sharply criticized the new ACC/AMA guidelines. Dr Redberg wrote that the guidelines will lead to a 70% increase in the number of healthy people for whom statins are recommended and pointed to a lack of evidence for statin use in certain subgroups of women. Dr Mertz asked rhetorically, “Should we withhold treatment for women due to low precision in a trial that was not designed to answer this question?” She added that “The absence of specific data not the same as negative data.”

Dr Mertz stated that some of the strongest evidence for use of statins in women comes from the JUPITER trial published in 2008, which had 6801 women and 11,001 men. This primary prevention trial found that rosuvastatin significantly reduced cardiovascular events in individuals who have elevated levels of the inflammatory biomarker high-sensitivity C-reactive protein but who do not have high levels of LDL-C. The trial was stopped early due to the substantial treatment effect. She concluded her presentation by stating, “It’s time to stop comparing women to men.” Funding for breast cancer research is $674 million for 40,000 deaths annually, while women’s CVD research funding is $173 million for 419,000 annual deaths.

Another presenter, Jennifer G. Robinson, MD, MPH, professor, Department of Epidemiology, Division of Cardiology, University of Iowa, spoke about the available evidence for lipid lowering in the elderly population. The new ACC/AHA guidelines include a risk calculator to help determine the 10-year risk for ASCVD.¹ The calculator is based on age, race, gender, total cholesterol level, high-density lipoprotein cholesterol, systolic blood pressure, and whether someone has diabetes, smokes, or is currently being treated for high blood pressure. The maximum age for the calculator is 79 years.¹ The elderly population is a high-risk group that can benefit from statins, she said. Dr Robinson also referred to the JUPITER trial, noting that there is strong evidence for statin therapy to reduce ASCVD risk for those over the age of 75 years with clinical ASCVD. There is less evidence for high-intensity statin therapy. For those without clinical CVD over 75 years of age, clinical judgment is required. Among JUPITER participants aged 50 to 69 years, the hazard ratio (HR) was .51 for the primary end point of first-ever myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death. For those aged 70 to 79 years, the HR was .61. The data were less accurate in the group that was 75 to 79 years of age, she said. Dr Robinson said more data are needed through an increased representation in clinical trials to determine the benefit in this high-risk population.

Karol Watson, MD, PhD, FACC, cardiologist, Geffen School of Medicine, director, Center for Cholesterol and Hypertension Management, associate professor of medicine, University of Southern California, Los Angeles, spoke about the available data in ethnic populations. JUPITER has some evidence, she said. She said that the degree of risk determines the benefit with statins, not ethnicity or gender. She added that there are many confounding factors. In minority populations, there is less screening, and fewer individuals are aware of their health status. One of the common issues she sees is that patients are believed to have statin intolerance because they have elevated levels of creatinine kinase. However, there are genetic differences by race. Among African Americans, the creatinine kinase levels are higher at baseline. Regarding the Asian population, there are differences in statin metabolism versus non-Asians. Data suggest that the lipid-lowering efficacy of statins is achieved at lower doses, she told attendees. Many treatment-related issues vary by race, she added, such as adherence and access to therapies. In her conclusion, Dr Watson noted that statins are effective in a broad range of patient populations and there is no evidence of decreased efficacy by race or ethnicity; however, healthcare providers should be aware that unique aspects of race and ethnic groups may affect treatment decisions.

References

1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published online November 2013]. Circulation. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a.citation.
2. Don’t give more patients stains. The New York Times. The Opinion Pages. November 13, 2013. http://www.nytimes.com/2013/11/14/opinion/dont-give-more-patients-statins.html?hp&rref=opinion.