With that question in mind, a recent study on statin intensity and mortality found a graded inverse relationship between high-intensity statin doses (for example, atorvastatin 40-80mg daily and rosuvastatin 20-40mg daily) and mortality—which goes along with the current literature that high-intensity statins are better for the secondary prevention of ASCVD12.
The study went a step further and showed that higher doses of high-intensity statins (for example, atorvastatin 80mg or rosuvastatin 40mg) therapy were associated with improved outcomes over the lower doses of high-intensity therapy (for example, atorvastatin 40mg or rosuvastatin 20mg)12.
Moreover, the 2013 guidelines did not recommend non-statin therapies, and left their use up to the clinician’s judgment. This spawned controversy. Many institutions and physicians avoid the use of non-statin drugs, such as ezetimibe. However, since the publication of the 2013 ACC guidelines, several studies have shown their benefits. This resulted in a consensus statement from the ACC, endorsed by the National Lipid Association, on the use of non-statin therapy to clarify the previously vague suggestions of the 2013 guidelines11.
Briefly, the new document maintains the four benefit groups originally described in 2013, but takes a step further. It also recommends lifestyle changes, monitoring for therapeutic response and adherence, with referrals to lipid specialists, ezetimibe, bile acid sequestrants and the novel PCSK9 inhibitor use that were recently approved by the FDA. While the consensus still recommends percent LDL-C reduction, the authors added a statement suggesting that physicians may consider absolute LDL reductions or LDL targets, as previously defined in ATP III11.
With regards to PCSK9 inhibitors, these monoclonal antibodies were developed to treat patients with familial hypercholesterolemia and intact LDL receptors. These are patients who would otherwise need plasmapheresis, or who have LDLs far above guideline limits despite maximal therapy with statins and ezetimibe18. Yet, PCSK9 inhibitors are being prescribed to patients who don’t reach their lipid goals, but are nonetheless close to target. Is this overkill?
An industry-sponsored study published in MedPage Today, November 15, 2016, addresses that question. For the study, patients with angiographically established CAD who were already on chronic statin therapy, but still had LDL levels of either 80 mg/dL or higher or between 60-80mg/dL, were randomized to receive treatment with a PCSK9 inhibitor or a placebo. Results at 78 weeks showed that 64% of the PCSK9 group had significant plaque regression compared with 47% in the placebo group19. This appears to be significant—but is it clinically significant? However, that study, like many others, was not designed to show the effect of PCSK9 therapy on clinical outcomes.
With an estimated price tag of $14,350 per year for PCSK9 inhibitors20, treating all patients who simply don’t meet their lipid goals with the addition of this drug seems a bit excessive—especially in light of how little data there is on long-term outcome. Exercise and a healthy diet, on the other hand, have been shown to reduce cardiovascular disease and prevent adverse cardiovascular events even in the face of genetic predispositions21. Best of all, those interventions are cheap!
With the sudden surge of publications on lipids over the past year, and particularly at the AHA Annual Scientific Session this month, we seem to be moving in the right direction toward finding how to best treat our patients. But we’re not home yet. Important questions regarding the primary prevention of CAD remain unanswered and the safety of lifelong statin use is still unclear. As we move forward into a still uncertain healthcare system, we need to be mindful of the cost of novel therapies — such as PCSK9 inhibitors — and consider what metrics most accurately can judge their efficacy. Dyslipidemia remains a huge public health concern. It is the underlying pathology that leads to clinically significant CAD and poor outcomes.
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- Juonala M, Viikari J, Kähönen M, et al. Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study. Eur Heart J. 2010;31(41):1745-1751.
- Gidding S. Assembling evidence to justify prevention of atherosclerosis beginning in youth. Circulation. 2010;122(24):2493-2494.
- Stone N, Robinson J, Lichtenstein A, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation. 2013;01.cir.0000437738.63853.7a
- Ades P. A controversial step forward: A commentary on the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Coron Artery Dis. 2014;25(4):360-363.
- US Preventive Services Task Force. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(19):1997-2007.
- Redberg R, Mitchell K. Statins for primary prevention – the debate is intense, but the data are weak. JAMA. doi:10.1001/jamainternmed.2016.7585
- American College of Cardiology. 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. JACC. 2016;68(1):92-125.
- O’Riordan M. New cholesterol guidelines abandon ldl targets. Medscape. Updated November 14, 2013. Available at: http://www.medscape.com/viewarticle/814152. Accessed on November 15, 2016.
- Virani S, Woodard L, Wang D, et al. Correlates of repeat lipid testing in patients with coronary heart disease. JAMA Intern Med. 2013;173(15):1439-1444.
- Virani S, Pokharel Y, Steinberg L, et al. Provider understanding of the 2013 ACC/AHA cholesterol guideline. J Clin Lipidol. 2016;10(3):497-504.
- Maddox T, Borden, W, Tang F, et al. Implications of the 2013 ACC/AHA cholesterol guidelines or adults in contemporary cardiovascular practice: insights from the NCDR PINNACLE registry. J Am Coll Cardiol. 2014;64(21):2183-2192.
- Miller D. Fear of statins. CMAJ. Sep 2009;181(6-7):399.
- Rodriguez F, Maron D, Knowles J, Virani S, Lin S, Heidenreich P. Association between intensity of statin therapy and mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. Nov 2016; doi:10.1001/jamacardio.2016.4052
- Susman E. ESC: PCSK9 Tx — Ready for Prime Time or Still Unproven? MedPage Today. Updated Oct 14, 2016. Available at: http://www.medpagetoday.com/clinicalfocus/pcsk9/60798?xid=NL_MPT_CF_PCSK9_2016-10-24&eun=g1072873d0r. Accessed November 15, 2016.
- Nissen SE. Global assessment of plaque regression with a PCSK9 antibody as measured by intravascular ultrasound. GLAGOV. ACC Abstract. Updated November 2016. Available at: http://www.acc.org/latest-in-cardiology/clinicaltrials/2016/11/14/00/18/glagovutm_source=accupdate&utm_medium=email_newsletter&ut m_campaign=accupdate_AHA16&utm_content=20161115#sthash.eDi8DpTU.dpuf. Accessed November 15, 2016.
- Kazi D, Moran A, Coxson P, et al. Cost-effectiveness of PCSK9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. JAMA. 2016;316(7):743-753.
- Khera A, Emdin C, Drake I, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. 2016; doi: 10.1056/NEJMoa1605086