I recently viewed a social media post that was so replete with misinformation, that it made my head spin. It was from an individual (not a physician) who was pontificating about how statin therapy was harmful and had no use in medicine. He did have a background in a field that involves musculoskeletal wellness, but the nature of his expertise was far from the subject about which he dogmatically spoke. This caused me to ponder this issue more broadly. In an age of easy access to information, the spread of medical misinformation has become an increasingly pervasive issue. Many individuals, perhaps with a profession tangential to management of medical illness, or just individuals “who have done their own research” may hold strong convictions about the efficacy of certain treatments—like the rejection of statins, despite overwhelming evidence supporting their benefit in reducing cardiovascular risk. These individuals often speak with an air of certainty, presenting themselves as experts on topics far outside their specific scope of training.
This phenomenon, where individuals without formal expertise promote their personal beliefs as if they are irrefutable truths, is not only a source of frustration for those with legitimate knowledge, but also dangerous for the public. It can foster confusion, harm, and mislead those seeking reliable, evidence-based healthcare advice. In this post, we will explore the psychological underpinnings of this dogmatic mindset, examine the role of disinformation, and underscore why credentials and experience matter when it comes to health and wellness.
The Psychology of Dogmatism
Psychologists have long been interested in the nature of dogmatism—an unwavering belief in one’s views, despite contrary evidence. According to Rokeach (1960), dogmatic individuals are highly resistant to change in their beliefs, which they consider absolute and unquestionable. The phenomenon is linked to a need for cognitive closure, a psychological desire for certainty and decisiveness in thinking. This is especially pronounced in domains like health and wellness, where individuals may seek to simplify complex medical topics to fit their own worldview.
A study by Clarke et al. (2014) found that dogmatic people often reject conflicting evidence because it creates discomfort. In this context, when an allied health professional specializing in musculoskeletal health, for instance, dismisses statins despite extensive evidence showing their life-saving benefits, it is often because acknowledging the complexity of medical science would challenge their own entrenched beliefs. Instead, they lean into simplifications, becoming more vocal in their certainty, regardless of their expertise or understanding of the broader body of evidence.
Disinformation: Intentions and Nefarious Influences
While some individuals may honestly believe they are helping others by promoting their views, others are more motivated by personal interests—be they financial, ideological, or political, or just to receive more “likes” on social media. The spread of health disinformation is often driven by a mix of unqualified individuals selling products or services, or by individuals with ideological agendas that reject mainstream medical consensus.
According to Lewandowsky, Ecker, and Cook (2017), disinformation is most effective when it plays on emotional triggers and confirmation bias. In the case of statins, for example, the narrative that “big pharma is pushing dangerous drugs” can be very alluring to people who are already skeptical of the medical establishment. For someone with no expertise in cardiology, this narrative is easy to latch onto, and the allure of challenging perceived authority figures makes their message more appealing.
When such figures speak dogmatically, they manipulate others into trusting them over professionals, leading to potentially harmful consequences, such as people foregoing statins or other evidence-based treatments. This is especially pernicious when the individuals promoting disinformation are well-spoken and confident, leveraging their charisma to sway public opinion.
The Nuance of Expert Knowledge
Experts in any field, particularly in healthcare, understand that knowledge is complex and evolving. Medical professionals, from doctors to dietitians, engage with continuous learning and critical thinking, taking into account the nuances of individual health and the broader context of scientific discovery. Statins, for instance, are not a one-size-fits-all solution. For some patients, alternative approaches may be appropriate, and for others, statins may be life-saving. A nuanced approach considers the individual’s overall health, history, and needs—rather than offering blanket statements.
In contrast, the non-expert who speaks dogmatically often ignores these complexities. Their message is reduced to simple slogans: “Statins are bad!” or “You don’t need them, try this herb!” This oversimplification does not only lack scientific merit—it actively harms the conversation by offering false certainty in an area where uncertainty is the norm.
A study by Gervais et al. (2017) highlights the importance of expertise in framing health messages. They found that lay individuals were far more likely to overestimate the certainty of their opinions, while experts were more likely to present information in a way that acknowledged uncertainty and context. The more nuanced and evidence-based approach is often less palatable in the age of soundbites, but it is ultimately more beneficial to public health.
Why Credentials and Experience Matter
Someone, for example, may be highly trained in the manipulation of the spine to address musculoskeletal issues. However, they are not trained to diagnose or treat systemic conditions like high cholesterol, heart disease, or diabetes. These are areas that require extensive education in physiology, pharmacology, and clinical care—subjects that go far beyond the scope of their training.
Credentials matter because they signify a level of education and expertise that equips individuals to make informed, evidence-based decisions. The role of a licensed physician, trained in internal medicine, family medicine, endocrinology or cardiology, involves years of education and practical experience in understanding complex biological systems, interpreting research, and providing care based on the best available evidence. However well-intentioned, often the pontificators in social media do not have the same training or understanding to offer medical advice on matters like statin therapy.
This difference in training explains why it’s essential to turn to professionals with the appropriate credentials when seeking advice about complex medical issues. It is important to understand that while an individual can help with musculoskeletal issues, they should not be presenting themselves as authorities on drugs that affect the cardiovascular system or other areas outside their expertise.
Conclusion
In conclusion, while it is tempting to trust confident voices that offer simplified solutions to complex health problems, it is essential to remember that dogmatism is not a substitute for expertise. The psychological appeal of certainty can easily overshadow the need for nuance and evidence-based care. Disinformation can be damaging when it undermines the credibility of legitimate experts, and individuals who speak authoritatively on topics they don’t fully understand should be approached with caution.
When it comes to health, knowledge and credentials matter. Medical professionals, who have the proper education and experience, are trained to navigate the complexities of human physiology and evidence-based medicine. It is crucial to rely on their expertise rather than the dogmatic declarations of individuals without the necessary qualifications. This is especially important in a rapidly changing political world which seems to have fostered a disdain for expertise. Always prioritize evidence over opinion, and remember that complexity and uncertainty are hallmarks of genuine medical knowledge.
References
• Clarke, C. E., et al. (2014). The relationship between cognitive closure and dogmatism. Journal of Research in Personality.
• Gervais, S. J., et al. (2017). The role of expertise in health messaging: A meta-analysis. Journal of Health Communication.
• Lewandowsky, S., Ecker, U. K. H., & Cook, J. (2017). Beyond Misinformation: Understanding and Coping with the Spread of False Beliefs. Psychological Science in the Public Interest.
• Rokeach, M. (1960). The Open and Closed Mind: Investigations into the Character of Human Belief. Basic Books.
As cardiovascular disease remains a leading cause of morbidity and mortality worldwide, optimizing lipid management is crucial for reducing atherosclerotic cardiovascular disease (ASCVD) risk. While statins are the cornerstone of lipid-lowering therapy, many patients require additional interventions to achieve target lipid levels or may not tolerate statins. This review examines the evidence for non-statin lipid-lowering therapies, including pharmacological agents, nutraceuticals, and dietary interventions.
Importance of MACE Data
When evaluating lipid-lowering therapies, it’s critical to focus on major adverse cardiovascular events (MACE) data rather than solely on lipid level changes. MACE typically includes a composite of cardiovascular death, non-fatal myocardial infarction (“heart attack”) and non-fatal stroke. Some studies also include hospitalization for unstable angina or coronary revascularization[13] (procedure to open clogged vessels). MACE endpoints provide a more clinically relevant measure of a therapy’s impact on patient outcomes compared to surrogate markers like LDL-C levels alone.
Pharmacological Agents
Ezetimibe
Mechanism: Ezetimibe inhibits intestinal cholesterol absorption by targeting the Niemann-Pick C1-Like 1 (NPC1L1) protein[5].
Efficacy: Ezetimibe typically reduces LDL-C by 15-20% when used as monotherapy (used alonea) and provides an additional 23-24% reduction when added to statin therapy[5][23].
Outcomes: The IMPROVE-IT trial demonstrated that adding ezetimibe to simvastatin in patients with recent acute coronary syndrome (emergency when blood flow to heart is reduced) reduced LDL-C by 24% and lowered the risk of cardiovascular events by 6.4% over 7 years[28].
Pleiotropic effects (not the primary effect or intention of drug) : Some studies suggest ezetimibe may have anti-inflammatory properties and improve endothelial function, though these effects are less well-established than for statins[42].
Bempedoic Acid
Mechanism: Bempedoic acid inhibits ATP citrate lyase (ACL), reducing cholesterol synthesis upstream of HMG-CoA reductase[21].
Efficacy: In statin-intolerant patients, bempedoic acid reduces LDL-C by 21% compared to placebo[21].
Outcomes: The CLEAR Outcomes trial showed a 13% relative reduction in MACE with bempedoic acid in statin-intolerant patients[21].
Pleiotropic effects: Bempedoic acid may have anti-inflammatory properties, as evidenced by reductions in high-sensitivity C-reactive protein (hsCRP)[21].
Colesevelam
Mechanism: Colesevelam is a bile acid sequestrant that binds bile acids in the intestine, leading to increased bile acid excretion and upregulation of LDL receptors[27].
Efficacy: Colesevelam reduces LDL-C by 15-18% as monotherapy and provides an additional 8-16% reduction when added to statin therapy[27].
Outcomes: While colesevelam improves lipid profiles, large-scale cardiovascular outcome trials are lacking[27].
Pleiotropic effects: Colesevelam has been shown to improve glycemic control in patients with type 2 diabetes, reducing HbA1c by 0.5-0.8%[22][41].
PCSK9 Inhibitors
Mechanism: PCSK9 inhibitors are monoclonal antibodies that prevent PCSK9-mediated degradation of LDL receptors, increasing LDL-C clearance from the bloodstream[40].
Efficacy: PCSK9 inhibitors can reduce LDL-C by 50-60% when added to statin therapy[40].
Outcomes: The FOURIER and ODYSSEY OUTCOMES trials demonstrated significant reductions in MACE with evolocumab and alirocumab, respectively, when added to statin therapy in high-risk patients[40].
Pleiotropic effects: PCSK9 inhibitors may have anti-inflammatory effects and improve endothelial function, though more research is needed to confirm these potential benefits[40].
Nutraceuticals and Supplements
Red Yeast Rice
Mechanism: Red yeast rice contains monacolin K, which is structurally identical to lovastatin and inhibits HMG-CoA reductase[19][24].
Efficacy: Red yeast rice can reduce LDL-C by 15-25% depending on the monacolin K content[19][24].
Outcomes: A meta-analysis of red yeast rice trials showed a 34% reduction in MACE and a 40% reduction in composite cardiac events[24].
Safety concerns: The FDA does not regulate red yeast rice products, leading to variability in monacolin K content and potential contamination with citrinin, a nephrotoxic mycotoxin[19].
Plant Sterols and Stanols
Mechanism: Plant sterols and stanols compete with cholesterol for intestinal absorption, reducing cholesterol uptake[6].
Efficacy: Consuming 2 grams of plant sterols or stanols daily can lower LDL-C by 5-15%[6][47].
Outcomes: While plant sterols and stanols improve lipid profiles, large-scale cardiovascular outcome trials are lacking[6].
Soluble Fiber
Mechanism: Soluble fiber binds bile acids in the intestine, leading to increased bile acid excretion and upregulation of LDL receptors[47].
Efficacy: Consuming 5-10 grams of soluble fiber daily can reduce LDL-C by 5-10%[47][49].
Outcomes: While soluble fiber improves lipid profiles, its direct impact on MACE has not been established in large-scale trials[49].
Efficacy: High-dose omega-3 fatty acids (4 grams daily) can reduce triglycerides by 30-50%[53].
Outcomes: The REDUCE-IT trial demonstrated a 25% relative risk reduction in MACE with 4 grams of icosapent ethyl (a highly purified EPA) in high-risk patients with elevated triglycerides[53].
Other Supplements
Several other supplements have shown potential lipid-lowering effects, though evidence for cardiovascular benefit is limited:
Berberine: May reduce LDL-C by 20-30%[10]
Garlic extract: May modestly reduce total cholesterol and LDL-C[10]
Green tea extract: May have modest LDL-C lowering effects[10]
Niacin: Can increase HDL-C and lower triglycerides, but has not shown cardiovascular benefit in recent trials[53]
Dietary Interventions
Mediterranean Diet
The Mediterranean diet, characterized by high consumption of olive oil, fruits, vegetables, whole grains, and moderate consumption of fish and poultry, has been associated with improved cardiovascular outcomes[47][56].
Efficacy: While the direct impact on lipid levels varies, adherence to a Mediterranean diet has been associated with a 30% reduction in MACE in high-risk individuals[47].
Plant-Based Diets
Vegetarian and vegan diets have been shown to improve lipid profiles and may reduce cardiovascular risk[52].
Efficacy: A meta-analysis of randomized controlled trials found that vegetarian and vegan diets reduced total cholesterol by 7%, LDL-C by 10%, and apolipoprotein B by 14% compared to omnivorous diets[52].
Portfolio Diet
The Portfolio Diet combines several cholesterol-lowering foods, including plant sterols, soy protein, viscous fibers, and nuts[49].
Efficacy: The Portfolio Diet has been shown to reduce LDL-C by 20-30%, comparable to the effect of a low-dose statin[49].
Other Dietary Strategies
Replacing saturated fats with unsaturated fats can reduce LDL-C by 9-16%[47][49]
Increasing intake of fruits and vegetables may modestly improve lipid profiles[47]
Consuming 1.5-2 ounces of tree nuts daily can reduce LDL-C by 3-5%[49]
Conclusion
While statins remain the cornerstone of lipid-lowering therapy, a wide array of non-statin interventions can effectively improve lipid profiles and reduce cardiovascular risk. When selecting therapies, physicians should consider the strength of evidence for MACE reduction, individual patient characteristics, and potential pleiotropic effects. Combining pharmacological agents with evidence-based dietary interventions and nutraceuticals may provide additive benefits in managing dyslipidemia and reducing ASCVD risk.
As our understanding of lipid metabolism and cardiovascular disease continues to evolve, ongoing research into novel therapies and combinations will further refine our approach to lipid management. Physicians should stay informed about emerging evidence and guidelines to provide optimal care for patients at risk for ASCVD.
Sources [1] Pleiotropic effects of statin therapy: molecular mechanisms and … https://pmc.ncbi.nlm.nih.gov/articles/PMC2621332/ [2] Colesevelam for the treatment of bile acid malabsorption-associated … https://academic.oup.com/ecco-jcc/article-abstract/8/11/1471/356826?redirectedFrom=fulltext&login=false [3] Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic … https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.039415 [4] Red Yeast Rice for Hypercholesterolemia – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC6822657/ [5] Use of lipid-lowering therapy: the guidelines, the drugs or the patient? https://academic.oup.com/eurheartjsupp/article/24/Supplement_I/I29/6823824?login=false [6] [PDF] Nutrition Interventions for Adults with Dyslipidemia https://www.lipid.org/sites/default/files/files/NLA_2023_Nutrition_Interventions_for_Adults_with_Dyslipidemia.pdf [7] 11 Foods that Lower Cholesterol – Harvard Health Publishing https://www.health.harvard.edu/heart-health/11-foods-that-lower-cholesterol [8] Impact of Mediterranean Diet on Lipid Composition in the Colaus … https://pmc.ncbi.nlm.nih.gov/articles/PMC10650561/ [9] Effects of a Plant-Based Diet on Plasma Lipids – Stanford Medicine https://med.stanford.edu/nutrition/research/completed-studies/plant-based-diet.html [10] Supplements for Lipid Lowering: What Does the Evidence Show? https://pubmed.ncbi.nlm.nih.gov/37300664/ [11] Residual Risk Factors to Predict Major Adverse Cardiovascular … https://www.nature.com/articles/s41598-017-08741-0 [12] Cardiovascular benefits of lipid-lowering drugs apply across … https://www.escardio.org/The-ESC/Press-Office/Press-releases/cardiovascular-benefits-of-lipid-lowering-drugs-apply-across-ethnicities-and-reg [13] Major adverse cardiovascular events – Wikipedia https://en.wikipedia.org/wiki/Major_adverse_cardiovascular_events [14] Optimization of the MACE endpoint composition to increase power … https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1242845/full [15] Intensity of and Adherence to Lipid‐Lowering Therapy as Predictors … https://www.ahajournals.org/doi/10.1161/JAHA.122.025813 [16] Understanding the molecular mechanisms of statin pleiotropic effects https://pmc.ncbi.nlm.nih.gov/articles/PMC10119541/ [17] Safety and Efficacy of Colesevelam HCl in the Treatment of Elderly … https://pmc.ncbi.nlm.nih.gov/articles/PMC4033819/ [18] Ezetimibe: The Lower the LDL-C, the Better (Even for Total … https://www.acc.org/Latest-in-Cardiology/Articles/2016/03/09/06/50/Ezetimibe-The-Lower-the-LDLC-the-Better [19] Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to … https://pmc.ncbi.nlm.nih.gov/articles/PMC10221652/ [20] New drugs coming up in the field of lipid control https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-19/new-drugs-coming-up-in-the-field-of-lipid-control [21] Comparative Cardiovascular Benefits of Bempedoic Acid and Statin … https://www.jacc.org/doi/10.1016/j.jacc.2024.04.048 [22] Efficacy and Safety of Colesevelam in Patients With Type 2 Diabetes … https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/770320 [23] Ezetimibe therapy: mechanism of action and clinical update – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC3402055/ [24] Red Yeast Rice Preparations Reduce Mortality, Major … – Frontiers https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.744928/full [25] A historical, evidence-based, and narrative review on commonly … https://www.jlr.org/article/S0022-2275(23)00166-9/fulltext [26] Statin effects beyond lipid lowering—are they clinically relevant? https://academic.oup.com/eurheartj/article/24/3/225/2733886?login=false [27] Colesevelam hydrochloride: evidence for its use in the treatment of … https://pmc.ncbi.nlm.nih.gov/articles/PMC3426253/ [28] Ezetimibe – StatPearls – NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK532879/ [29] Red Yeast Rice for Hyperlipidemia: A Meta-Analysis of 15 High … https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.819482/full [30] Lipid-Lowering Therapies: A Review of Current and Future Options https://www.uspharmacist.com/article/lipidlowering-therapies-a-review-of-current-and-future-options [31] The Pleiotropic Effects of Lipid-Modifying Interventions – MDPI https://www.mdpi.com/2218-1989/14/7/388 [32] Colesevelam Hydrochloride (Cholestagel): A New, Potent Bile Acid … https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485105 [33] New Insights on Simvastatin and Ezetimibe in a Single Tablet https://www.ecrjournal.com/articles/new-insights-simvastatin-and-ezetimibe-single-tablet [34] Red yeast rice Information | Mount Sinai – New York https://www.mountsinai.org/health-library/supplement/red-yeast-rice [35] Lipid-Lowering Agents | Circulation Research – AHA Journals https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.118.313171 [36] Pleiotropic Effects of Statins on the Cardiovascular System https://www.ahajournals.org/doi/10.1161/circresaha.116.308537 [37] a double-blind, randomised, placebo-controlled, phase 4 clinical trial https://www.thelancet.com/journals/langas/article/PIIS2468-1253(22)00401-0/fulltext?dgcid=raven_jbs_aip_email [38] Projected Outcomes of Optimized Statin and Ezetimibe Therapy in … https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808802 [39] Efficacy of red yeast rice extract on myocardial infarction patients … https://www.nature.com/articles/s41598-020-59796-5 [40] Nonstatin Low-Density Lipoprotein–Lowering Therapy and … https://www.ahajournals.org/doi/10.1161/atvbaha.115.306442 [41] Colesevelam lowers glucose and lipid levels in type 2 diabetes https://dom-pubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1463-1326.2009.01181.x [42] Ezetimibe: cholesterol lowering and beyond – Taylor & Francis Online https://www.tandfonline.com/doi/full/10.1586/14779072.6.4.447 [43] Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.11.056 [44] Are We Using Ezetimibe As Much As We Should? – Sage Journals https://journals.sagepub.com/doi/10.1177/11772719241257410 [45] [PDF] Dietary intervention to lower serum cholesterol – RACGP https://www.racgp.org.au/getattachment/f8f6c03d-08b4-49b1-abb4-35039b0f4928/Lower-serum-cholesterol.aspx [46] How to Lower Cholesterol with Diet – MedlinePlus https://medlineplus.gov/howtolowercholesterolwithdiet.html [47] Does the Mediterranean Diet Have Any Effect on Lipid Profile … https://pmc.ncbi.nlm.nih.gov/articles/PMC10222807/ [48] Vegetarian and vegan diets may lower cholesterol levels https://www.health.harvard.edu/heart-health/vegetarian-and-vegan-diets-may-lower-cholesterol-levels [49] Diet and Exercise in the Management of Hyperlipidemia – AAFP https://www.aafp.org/pubs/afp/issues/2010/0501/p1097.html [50] Cholesterol – healthy eating tips – Better Health Channel https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/cholesterol-healthy-eating-tips [51] LDL cholesterol: Mediterranean diet may not affect levels https://www.medicalnewstoday.com/articles/does-a-mediterranean-diet-really-help-lower-bad-cholesterol [52] Vegetarian or vegan diets and blood lipids: a meta-analysis of … https://pubmed.ncbi.nlm.nih.gov/37226630/ [53] Alternative Treatments for High Cholesterol – WebMD https://www.webmd.com/cholesterol-management/high-cholesterol-alternative-therapies [54] Association between Dietary Intake and Lipid-Lowering Therapy https://pmc.ncbi.nlm.nih.gov/articles/PMC6724025/ [55] Prevention and Treatment of High Cholesterol (Hyperlipidemia) https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia [56] Mediterranean diet: MedlinePlus Medical Encyclopedia https://medlineplus.gov/ency/patientinstructions/000110.htm [57] The Role of Specific Components of a Plant-Based Diet in … https://pmc.ncbi.nlm.nih.gov/articles/PMC7551487/ [58] 6 common “heart-health” supplements ineffective at lowering … https://newsroom.heart.org/news/6-common-heart-health-supplements-ineffective-at-lowering-cholesterol-compared-to-statins [59] Nutrition interventions for adults with dyslipidemia – PubMed https://pubmed.ncbi.nlm.nih.gov/37271600/ [60] Effectiveness of altering serum cholesterol levels without drugs – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC1312230/ [61] The Impact of the Mediterranean Diet and Lifestyle Intervention on … https://www.mdpi.com/1422-0067/25/2/1338 [62] Portfolio Diet: Lower Your Cholesterol One Bite at a Time with Plant … https://www.orlandohealth.com/content-hub/portfolio-diet-lower-your-cholesterol-one-bite-at-a-time-with-plant-based-eating [63] 8 Natural Cholesterol Reducers – Healthline https://www.healthline.com/health/high-cholesterol/natural-cholesterol-reducers [64] Improving Your Cholesterol with Diet and Exercise | AAFP https://www.aafp.org/pubs/afp/issues/2010/0501/p1103.html [65] Mediterranean diet for heart health – Mayo Clinic https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801 [66] Top 10 Plant-Based Foods to Lower Cholesterol https://www.purelyplanted.com/post/top-10-plant-based-foods-to-lower-cholesterol [67] Best supplements for lowering cholesterol – MedicalNewsToday https://www.medicalnewstoday.com/articles/cholesterol-lowering-supplements [68] Cooking to Lower Cholesterol | American Heart Association https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cooking-to-lower-cholesterol [69] Can the Mediterranean Diet Lower Your Cholesterol? https://www.verywellhealth.com/mediterranean-diet-to-reduce-cholesterol-697647 [70] Plant-Based Diets and Your Cholesterol – WebMD https://www.webmd.com/cholesterol-management/features/plant-based-diets-and-cholesterol [71] Mediterranean Meal Plan to Lower Cholesterol – EatingWell https://www.eatingwell.com/article/7740264/mediterranean-meal-plan-to-lower-cholesterol/ [72] Lower cholesterol with a plant-based diet, study says – CNN https://edition.cnn.com/2023/05/24/health/vegetarian-vegan-diet-reduce-cholesterol-wellness/index.html [73] Lipid Management in Peripheral Artery Disease: A Focus on Recent … https://www.acc.org/Latest-in-Cardiology/Articles/2024/08/19/10/45/Lipid-Management-in-Peripheral-Artery-Disease [74] Association of Major Adverse Cardiac Events up to 5 Years in … https://www.ahajournals.org/doi/10.1161/JAHA.118.010541 [75] More- Versus Less-Intensive Lipid-Lowering Therapy – AHA Journals https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.118.005460 [76] Association of Treatment Intensity and Adherence to Lipid-Lowering … https://pmc.ncbi.nlm.nih.gov/articles/PMC8107155/ [77] Lipid-lowering therapies for cardiovascular disease prevention and … https://pmc.ncbi.nlm.nih.gov/articles/PMC10575662/ [78] Defining the need for cardiovascular event definitions https://academic.oup.com/ehjqcco/article/10/2/105/7596555 [79] Risk of major adverse cardiovascular events associated … – BMJ Open https://bmjopen.bmj.com/content/13/11/e064541 [80] Heart Failure and Major Adverse Cardiovascular Events in Atrial … https://www.mdpi.com/2227-9059/11/7/1825 [81] Occurence of First and Recurrent Major Adverse Cardiovascular … https://jamanetwork.com/journals/jamacardiology/fullarticle/2754760 [82] Comparison of Major Adverse Cardiac Events Between … https://jamanetwork.com/journals/jamacardiology/fullarticle/2738103 [83] Effectiveness of lipid-lowering therapy on mortality and major … https://pmc.ncbi.nlm.nih.gov/articles/PMC10660972/ [84] Navigating the “MACE” in Cardiovascular Outcomes Trials and … https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.13740 [85] Reductions in Atherogenic Lipids and Major Cardiovascular Events https://www.ahajournals.org/doi/10.1161/circulationaha.116.024604 [86] Prediction of Major Adverse Cardiovascular Events in Patients With … https://www.ahajournals.org/doi/10.1161/CIRCGEN.121.003546
Everyday (including today) I must build a case for the timely use of a statin agent, overcoming the vilification these medicines face in popular culture. In reality, compelling evidence, based on well conducted studies, have shown the profound beneficial effects of these medications. Indeed, statins have revolutionized cardiovascular disease prevention and treatment since their introduction. This post will delve into the wealth of data from statin trials, exploring their efficacy, pleiotropic effects, and key concepts like number needed to treat (NNT). We’ll also examine specific trials and rank statins by their power in reducing cardiovascular events.
Statin Efficacy: The Big Picture
Numerous large-scale trials have consistently demonstrated the efficacy of statins in reducing cardiovascular events. The evidence is particularly strong for secondary prevention (in patients with established cardiovascular disease) but is also significant for primary prevention in high-risk individuals[1][2].
Key findings from major statin trials include:
Reduction in major adverse cardiovascular events (MACE)
The Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) was a landmark study that demonstrated the benefits of statins in primary prevention[8][9]. This trial randomized hypertensive patients with relatively low cholesterol levels to atorvastatin 10 mg or placebo.
Key ASCOT-LLA findings:
36% reduction in the primary endpoint (non-fatal myocardial infarction and fatal coronary heart disease)
Early separation of event curves, suggesting rapid onset of benefit (in as few as 2 months)
Persistent benefit even after trial termination, indicating a potential “legacy effect”
The rapid separation of event curves in ASCOT-LLA is particularly intriguing. It suggests that statins may provide cardiovascular protection even before their full lipid-lowering effects are realized, supporting the concept of pleiotropic effects[8].
Pleiotropic Effects: Beyond Lipid-Lowering
Statins may exert cardiovascular protective effects independent of LDL-C lowering, known as “pleiotropic” effects[7]. These include:
Improved endothelial function (cells that line the arteries)
Antioxidant properties
Anti-inflammatory effects
Plaque stabilization
While some studies support these pleiotropic effects, the clinical relevance remains debated. Some trials have shown greater benefits with high-dose statins compared to lower doses plus ezetimibe, despite similar LDL-C lowering[7]. However, other studies have not found such differences, leaving the question of pleiotropy open to further research.
Number Needed to Treat (NNT)
The NNT is a valuable concept in understanding the real-world impact of statin therapy. It represents the number of patients who need to be treated to prevent one adverse event.
In the UK arm of ASCOT-LLA, the NNT to prevent one death from atorvastatin treatment for 3.3 years was 286[1]. This number improved over time, highlighting the cumulative benefit of statin therapy.
A meta-analysis of primary prevention trials found that treating 100 adults (aged 50-75 years) with a statin for 2.5 years prevented 1 MACE in 1 adult[2]. This translates to an NNT of 100 over 2.5 years for primary prevention.
Major Statin Trials: A Summary
4S (Scandinavian Simvastatin Survival Study): Demonstrated mortality (reducing death) benefit in secondary prevention with simvastatin[8].
WOSCOPS (West of Scotland Coronary Prevention Study): Showed pravastatin’s efficacy in primary prevention[2].
CARE (Cholesterol and Recurrent Events): Established pravastatin’s benefit in patients with average cholesterol levels post-MI[8].
LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease): Confirmed pravastatin’s long-term benefits in a broad range of patients[8].
JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin): Demonstrated rosuvastatin’s efficacy in primary prevention for patients with elevated C-reactive protein[2].
PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy): Compared aggressive (atorvastatin 80 mg) vs. moderate (pravastatin 40 mg) statin therapy[5].
ASCOT-LLA: Showed atorvastatin’s benefit in primary prevention for hypertensive patients[8][9].
Ranking Statins by Event Reduction
While all statins have shown efficacy, some appear more potent in reducing cardiovascular events:
Atorvastatin (high-intensity)
Rosuvastatin (high-intensity)
Simvastatin (moderate to high-intensity)
Pravastatin (low to moderate-intensity)
Fluvastatin (low-intensity)
This ranking is based on their lipid-lowering potency and evidence from comparative trials[3][5]. However, it’s important to note that individual patient factors should guide statin selection. Our preference is for rosuvastatin, due to less musculoskeletal effects and profound reduction of LDL, even at lower doses.
CVA vs. MACE Data
While statins consistently reduce MACE, or major adverse cardiac events, (which typically includes cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), their effect on cerebrovascular accidents (CVA) alone is less pronounced.
Most trials show a significant reduction in overall MACE, but the effect on stroke (CVA) is often smaller or non-significant when analyzed separately. For instance, in ASCOT-LLA, while there was a significant reduction in MACE, the reduction in fatal and non-fatal stroke was not statistically significant[8][9].
In conclusion, the wealth of data from statin trials provides strong evidence for their efficacy in reducing cardiovascular events, particularly in high-risk individuals and for secondary prevention. While questions remain about the extent of their pleiotropic effects and the optimal approach to primary prevention, statins remain a cornerstone of cardiovascular risk reduction. As with all medical interventions, the decision to initiate statin therapy should be based on individual patient factors and shared decision-making.
Sources [1] 11-year mortality follow-up of the lipid-lowering arm in the UK … https://academic.oup.com/eurheartj/article/32/20/2525/487760?login=false [2] Evaluation of Time to Benefit of Statins for the Primary Prevention of … https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2773065 [3] Comparative Effectiveness of Statin Therapy in Reducing … https://www.heraldopenaccess.us/openaccess/comparative-effectiveness-of-statin-therapy-in-reducing-cardiovascular-events [4] Ongoing Clinical Trials of the Pleiotropic Effects of Statins – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC1993933/ [5] Improving outcomes through statin therapy – a review of ongoing trials https://academic.oup.com/eurheartjsupp/article/6/suppl_A/A28/386696 [6] Time to Benefit of Statins for Primary Prevention of Cardiovascular … https://www.acc.org/latest-in-cardiology/journal-scans/2020/11/24/18/25/evaluation-of-time-to-benefit-of-statins [7] Pleiotropic Effects of Statins on the Cardiovascular System – PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC5467317/ [8] Long-term results from statin trials: answers but more unresolved … https://academic.oup.com/eurheartj/article/32/20/2479/487295 [9] Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2010/02/22/19/05/ASCOT–Lipid-Arm
