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Statins and Primary Prevention

Statins and Primary Prevention

• The absolute CVD (cardiovascular disease) risk reduction is 10 times greater and serious side-effects 100 times lower with statin therapy than for low dose aspirin in primary prevention (people without heart disease). Intensive statin therapy appears to be far safer than low dose aspirin and the risk benefit analysis supports the use of statin before aspirin in primary prevention of CVD.1

• The risks and benefits of aspirin in primary prevention balance each other or may result in net harm in many people, who are already on a statin. The overwhelming benefit and miniscule risk from statins in primary prevention and in diabetes is well established and continues to mount.1

• The benefits of statins on reducing nonfatal events are considerable and may be missed by those focusing only on fatal events.2, 3 Many skeptics who have focused on the lack of effect of statins on total mortality have conveniently ignored the fact that CAD accounts for only 17% of total mortality in North America and Western Europe.4 Thus statins are not expected to have any impact on >80% of all deaths. They also ignore the value of avoiding a stroke, heart attack, and bypass surgery at a young age and enjoying a life without serious disabilities.

• The JUPITER trial is a gift that keeps on giving convincing evidence regarding safety and efficacy of statins in relatively low-risk middle-aged and older men and women. Among adults with LDL-C

• Among four prespecified subgroups (people with metabolic syndrome, Framingham risk score ≤10%, nonwhites, and smokers) the benefit was not seen unless the on-treatment LDL-C was

• Further analysis of JUPITER was conducted by Ridker et al, evaluating absolute risk reductions in the primary end points with determination of the number needed to treat (NNT). This demonstrated that for the end point of heart attack, stroke, revascularization, or death, the 5-year NNT on the basis of the data from JUPITER was 20. All subgroups had 5-year NNT values for this end point

• Notably, the NNT was 37 for subjects with Framingham risk score300). This observation suggests a possible role of nontraditional risk markers such as hsCRP (high-sensitivity C-reactive protein) to help determine eligibility for statin therapy for primary prevention in women as well as men who meet the eligibility criteria of JUPITER.6 However others have questioned the value of hsCRP in selecting patients for statin therapy.7

• Absolute risk reductions and consequent NNT values associated with statin therapy among those with elevated hsCRP and LDL-C are comparable if not superior to published NNT values for several widely accepted interventions for primary cardiovascular prevention, including the use of statin therapy among those with overt hyperlipidemia.

• The absolute risk reduction of the incidence of heart attack, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or confirmed death from cardiovascular causes, was 48% greater in subjects aged ≥70 years (0.77 vs 0.52 events per 100 patient-years). The NNT for 4 years to prevent 1 primary end point was 24 in this population, compared to 36 in patients aged 50 to 69 years.8 Hazard reduction rates were similar in men and women in this older cohort.

• Patients in the rosuvastatin group had lower rates of adverse events compared to the placebo group but demonstrated higher rates of muscle weakness, stiffness, or pain; renal disorder; bleeding events; gastrointestinal disorder; hepatic disorder; and incident diabetes. However, none of these associations were statistically significant.8

• The statin revolution is analogous to the revolution in computer technology. Over the last 20 years, the processing power of computers has increased more than 100-fold but the price has also come down by at least 10-fold. Many statins are now available for $4 a month in the US, down from $4 a day. These low-cost low-potency statins can lower LDL-C by 40%. Atorvastatin can lower LDL-C by 60% and will become generic (with dramatic drop in price) by the end of 2011.

• With the new pricing of the statins, low-cost statins are cost-effective (and even cost saving) for most persons >35 years of age with modestly elevated cholesterol or any CVD risk factors, regardless of the LDL-C level. Lowering thresholds to >130 mg/dL for persons with no risk factors and >100 mg/dL for persons with one risk factor (down from 160 mg/dl recommended in NCEP), along with treating all moderate and moderately high-risk persons would further lower CAD burden for $9900 per quality-adjusted life-year (QUALY). For comparison, the cost of QUALY for dialysis currently averages $129,090 per QUALY.9

• CVD remains a significant cause of death and disability, particularly in the sizable and rapidly growing segment of the population aged >65 years. Treatment with statins has well-documented benefits in the primary and secondary prevention of CVD. However, a growing body of evidence suggests that statin therapy is underused, particularly in older patients and women.

• The emerging data reviewed herein provide an evidence-based argument for the utility of statin therapy in asymptomatic women and older adults who might still be at significant risk for future cardiovascular events.

Statins and children

• The American Heart Association recommends drug therapy in children >10 years of age, whereas the American Academy of Pediatrics now recommends drug therapy for dyslipidemia for children >8 years of age (including girls before menarche).1, 10, 11

• The objective of statin therapy in children is to prevent the development and progression of the plaque (rather than preventing a heart attack at this young age) and delay the development of CVD.1

• Children with very high cholesterol levels develop atherosclerosis and progress rapidly in early teenage years. Statin therapy has been shown to induce a significant regression of carotid atherosclerosis with no adverse effects on growth, sexual maturation, hormone levels, liver or muscle.12, 13 Increased cholesterol levels may affect the aortic valve; aortic regurgitation may be the earliest sign of accelerated atherosclerosis in children.13

• The threshold of intervention in children is an LDL-C >190 mg/dL in the absence of any other risk factors, or >160 mg/dL in the presence of a positive family history of premature CVD or 2 other risk factors. The minimal LDL goal is <130 mg/dL and ideal goal is <110 mg/dL. The threshold of intervention for LDL-C is 30 mg/dL lower for Indians than Americans and Europeans.10


1. Enas E.A., Hancy Chennikkara Pazhoor MD, Arun Kuruvila MBBS, Krishnaswami Vijayaraghavan MD F. Intensive Statin Therapy for Indians:Part I Benefits. Indian Heart J 2011; 63: 211-227.
2. Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. Bmj. 2009;338:b2376.
3. Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. Nov 25 2008;52(22):1769-1781.
4. Ray K K, Seshasai SR, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. Jun 28 2010;170(12):1024-1031.
5. Hsia J, Macfadyen JG, Monyak J, Ridker PM. Cardiovascular Event Reduction and Adverse Events Among Subjects Attaining Low-Density Lipoprotein Cholesterol 6. Ridker PM, MacFadyen JG, Fonseca FA, et al. Number needed to treat with rosuvastatin to prevent first cardiovascular events and death among men and women with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER). Circ Cardiovasc Qual Outcomes. Nov 2009;2(6):616-623.
7. Blaha MJ, Budoff MJ, DeFilippis AP, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. Aug 20 2011;378(9792):684-692.
8. Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. Apr 20 2010;152(8):488-496, W174.
9. Lee CP, Chertow GM, Zenios SA. An empiric estimate of the value of life: updating the renal dialysis cost-effectiveness standard. Value Health. Jan-Feb 2009;12(1):80-87.
10. McCrindle BW, Urbina EM, Dennison BA, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation. Apr 10 2007;115(14):1948-1967.
11. Daniels SR, Greer FR. Lipid screening and cardiovascular health in childhood. Pediatrics. Jul 2008;122(1):198-208.
12. Wiegman A, Hutten BA, de Groot E, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. Jama. Jul 21 2004;292(3):331-337.
13. McCrindle BW, Ose L, Marais AD. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr. Jul 2003;143(1):74-80.

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