In an invited editorial published in the current issue of Trends in Cardiovascular Medicine, researchers from Florida Atlantic University’s Schmidt College of Medicine urge practicing cardiologists to achieve lower LDL cholesterol levels beginning with the highest doses of the most potent statins, namely rosuvastatin and atorvastatin. The authors emphasize that high-potency statins should be the primary pharmacologic in the treatment of cardiovascular disease as adjuncts to therapeutic lifestyle changes.
The researchers emphasize that therapeutic lifestyle changes will be effective in the absence and presence of adjunctive therapies in treating and preventing cardiovascular diseases. Lifestyle changes of proven benefit include avoidance or cessation of cigarette smoking, achieving and maintaining healthy body weight and blood pressure, regular physical activity, and restricting alcohol consumption.
Despite the proven effectiveness of therapeutic lifestyle changes, approximately 40% of adults in the United States have metabolic syndrome, a constellation of risk factors including obesity, hypertension, dyslipidemia, and insulin resistance. These individuals have a cardiovascular risk equivalent to those with prior heart attacks or strokes, yet many are underdiagnosed and undertreated.
The authors also underscore that only about 21% of Americans meet the minimum daily requirement for physical activity, and that meaningful increases in physical activity are possible at any age, including among older adults.
Based on the robust totality of randomized trial data and their meta-analyses, the authors conclude that statins – particularly rosuvastatin and atorvastatin – have the strongest and most consistent body of evidence supporting their prescription in treatment and prevention in both men and women including older adults.
Because most patients tend to stay on their initially prescribed statin dose, the authors recommend that cardiologists consider starting therapy with the highest dose of these agents and titrating down if necessary. They also highlight that the benefits of statins and aspirin are at least additive and potentially synergistic. Most secondary prevention patients should be prescribed aspirin. In primary prevention, however, individual clinical judgments are necessary, and aspirin should be considered after statins – and if the residual risk of occlusion exceeds that of major bleeding, predominantly gastrointestinal.
“Practicing cardiologists may wish to consider that all adjunctive drug therapies to therapeutic lifestyle changes should be added only after achieving maximal doses of statins. Further, statins have the largest and most persuasive body of evidence of any pharmacological adjunctive therapy in treatment and prevention of cardiovascular disease,” said Charles H. Hennekens, M.D, FACC, senior and corresponding author and the first Sir Richard Doll Professor of Medicine and Preventive Medicine, and interim chair, Department of Population Health, Schmidt College of Medicine.
The researchers offer cautious views of adjunctive therapies such as ezetimibe and evolocumab, which tend to be used more widely than optimal. For example, in the IMPROVE-IT trial, the addition of ezetimibe to simvastatin showed only a minor benefit, while the FOURIER trial demonstrated evolocumab’s efficacy in secondary prevention only in patients with familial hypercholesterolemia already on maximal statin doses. While FOURIER was a completed trial of secondary prevention, ILLUMINATE is an ongoing trial in high-risk primary prevention patients with familial hypercholesterolemia.
“These findings suggest that such therapies may be more appropriately reserved for select high-risk patients who have not achieved LDL goals with statins alone,” said Hennekens.
The authors also discuss the role of omega-3 fatty acids, noting that earlier trials were positive but later tended to show no net benefit. The authors opine that this may have been due to widespread statin use. They note that in REDUCE-IT, a large-scale randomized trial, icosapent ethyl was the only omega-3 fatty acid to demonstrate significant added benefits when added to evidence-based doses of high potency statins. Patients assigned at random to icosapent ethyl, a purified form of eicosapentanoic acid, experienced a significant 25% reduction in major cardiovascular events, with a number needed to treat of just 21.
Hennekens also reflected on the enduring relevance of Benjamin Franklin’s 1736 observation that “an ounce of prevention is worth a pound of cure.”
First author of the editorial is John Dunn, a third-year medical student in the Schmidt College of Medicine.
- FAU -
About the Charles E. Schmidt College of Medicine:
Florida Atlantic University’s Charles E. Schmidt College of Medicine is one of approximately 159 accredited medical schools in the U.S. The college was launched in 2010, when the Florida Board of Governors made a landmark decision authorizing FAU to award the M.D. degree. After receiving approval from the Florida legislature and the governor, it became the 134th allopathic medical school in North America. With more than 170 full and part-time faculty and more than 1,300 affiliate faculty, the college matriculates 80 medical students each year and has been nationally recognized for its innovative curriculum. The college offers M.S. (thesis and non-thesis) and Ph.D. programs in biomedical science, along with a certificate in genomics and precision medicine. Taught by top researchers, the curriculum combines cutting-edge coursework with hands-on learning, preparing graduates for careers in medicine, research, industry, and academia. To further Florida Atlantic’s commitment to increase much needed medical residency positions in Palm Beach County and to ensure that the region will continue to have an adequate and well-trained physician workforce, the FAU Charles E. Schmidt College of Medicine Consortium for Graduate Medical Education (GME) was formed in fall 2011 with five leading hospitals in Palm Beach County. The consortium currently has five Accreditation Council for Graduate Medical Education (ACGME) accredited residencies including internal medicine, surgery, emergency medicine, psychiatry, and neurology, and five fellowships in cardiology, hospice and palliative care, geriatrics, vascular surgery, and pulmonary disease and critical care medicine. The college also manages the Florida Atlantic University Medical Group, offering comprehensive primary care, and the Marcus Institute of Integrative Health specializes in integrative pain management, precision therapies, and mental health. A 2023 partnership with Broward Health expands academic medicine, clinical training, and research opportunities.
About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, Florida Atlantic serves more than 30,000 undergraduate and graduate students across six campuses located along the Southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, Florida Atlantic embodies an innovative model where traditional achievement gaps vanish. Florida Atlantic is designated as a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report, and holds the designation of “R1: Very High Research Spending and Doctorate Production” by the Carnegie Classification of Institutions of Higher Education. Florida Atlantic shares this status with less than 5% of the nearly 4,000 universities in the United States. For more information, visit www.fau.edu.
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