By David Fiore, MD

Professor of Family Medicine, University of Nevada, Reno

Dr. Fiore reports no financial relationships relevant to this field of study.

SYNOPSIS: In an examination of the data from the much-publicized Systolic Blood Pressure Intervention Trial (SPRINT), the author found no benefit of statin therapy for primary prevention of cardiovascular events or all-cause mortality.

SOURCE: Huesch MD. Association of baseline statin use among older adults without clinical cardiovascular disease in the SPRINT trial. JAMA Intern Med 2018 Jan 22. doi: 10.1001/jamainternmed.2017.7844. [Epub ahead of print].

One of the most remarkable advances in cardiovascular medicine must be the use of statin drugs to lower cardiovascular risks. In previous studies, statin therapy has been shown to lower the relative risk of cardiovascular events consistently by approximately 20-25%. However, these studies were not designed specifically to assess elderly subjects.

Huesch attempted to re-examine the data of the widely discussed Systolic Blood Pressure Intervention Trial (SPRINT), looking only at those > 70 years of age (or 65 years of age for the sensitivity analysis). SPRINT, which was published in 2015, was designed to compare intensive vs. standard blood pressure control in non-diabetic patients with increased cardiovascular risk.1 Approximately one-third of the participants in SPRINT were > 70 years of age (3,054 of 9,361). Of these, 1,350 were taking a statin at baseline. Huesch did not find any statistically significant differences in primary endpoint between the patients on a statin vs. those who were not.

Unfortunately, there were significant differences between those on a statin at baseline and those who were not. Among these differences, those on a statin were more likely to be male, have chronic kidney disease, present with a higher body mass index, register higher glucose readings, and demonstrate lower Framingham risk scores. Adjusting for these factors, Huesch still did not find any statistically significant differences in outcomes based on prior statin use.

COMMENTARY

Sadly, this analysis does not leave us with a definite answer as to whether we should recommend statin therapy for primary prevention in the elderly. Although the population was large and part of a carefully crafted study, this is a secondary analysis of a non-randomized intervention. The results and conclusions are consistent with another post hoc analysis, this one of the Lipid-Lowering Trial, which was a component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.2

On the other hand, as Huesch noted, the authors of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and the Heart Outcomes Prevention Evaluation (HOPE) trials found a benefit from treating the elderly with statins.3,4 The authors of various review articles and meta-analyses also have touted a benefit of statin treatment in the elderly.5-7

Such investigators tended to find some benefit in preventing cardiovascular events but not mortality. Furthermore, their analyses typically included more “young elderly” (65-75 years of age) than very elderly (> 75 years of age). To add confusion to this subject, the Atherosclerotic Cardiovascular Disease Risk Calculator, released in 2017 by the American College of Cardiology/American Heart Association, excludes patients > 79 years of age.

As the U.S. population continues to age and experiences more comorbid illnesses, the question of when to add or remove therapy becomes increasingly urgent. Unfortunately, this study may just add to our confusion, and we may need to wait until the results of the Australian STAtin Therapy for Reducing Events in the Elderly (STAREE) study are released to get a definitive answer. Even then, it is likely that the “answer” won’t be so definitive. What do we do in the meantime? We know that cardiovascular events increase as one ages and that statins can lower the risk of these events. What we don’t know is when the harm of another medication outweighs the benefits. Furthermore, there seem to be some elderly patients who, despite their elevated lipids, remain free of cardiac disease.

Therefore, a rational approach may be to: 1) use caution when starting statin therapy for primary prevention in the elderly (especially those > 75 years of age); 2) consider stopping statin therapy in the very elderly if they have never experienced a cardiac event; and 3) consider using a calcium score to determine whether to continue statin therapy for primary prevention in those between 65 and 79 years of age, although this approach is not based on study data.

REFERENCES

  1. SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-2116.
  2. Han BH, Sutin D, Williamson JD, et al; ALLHAT Collaborative Research Group. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: The ALLHAT-LLT randomized clinical trial. JAMA Intern Med 2017;177:955-965.
  3. Ridker PM. The JUPITER trial: Results, controversies, and implications for prevention. Circ Cardiovasc Qual Outcomes 2009;2:279-285.
  4. Yusuf S, Bosch J, Dagenais G, et al; HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2021-2031.
  5. Teng M, Lin L, Zhao YJ, et al. Statins for primary prevention of cardiovascular disease in elderly patients: Systematic review and meta-analysis. Drugs Aging 2015;32:649-661.
  6. Reiner Z. Primary prevention of cardiovascular disease with statins in the elderly. Curr Atheroscler Rep 2014;16:420.
  7. Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: A meta-analysis. J Am Coll Cardiol 2013;62:2090-2099.