February 1, 2018

Statins: When Do the Benefits Outweigh the Risks in the very Elderly?

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by Taylor J Neeley and Lisa C Hutchison, PharmD, MPH, UAMS

High quality studies show that statins significantly reduce all-cause mortality in older patients with established cardiovascular disease (CVD). One meta-analysis included approximately 20,000 patients between ages 65 and 82 with coronary heart disease who received either placebo or statin. There was a 22% decrease in all-cause mortality over 5 years in the statin group vs. placebo. The meta-analysis also revealed significant risk reductions in cardiovascular mortality, nonfatal myocardial infarction, and strokes of around 30% each. 1

However, the benefits for patients 75 years and older without CVD are less clear because major statin trials have excluded patients greater than 75. Very few trials have included patients over 70 years of age, and evidence for patients >80 is largely limited and conflicting.2 For example, in the Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial (ALLHAT-LLT), initiation of pravastatin 40 mg for primary prevention in patients 65 years and older showed no risk reduction in cardiovascular events.4 However, in the Prospective Study of Pravastatin in Elderly at Risk (PROSPER) trial, patients of ages 70-82 with at least one cardiovascular risk factor (hypertension, smoking, and/or diabetes) were randomized to either pravastatin 40 mg or placebo. There was a significant reduction in major vascular events (stroke, fatal or non-fatal MI) in pravastatin group vs. placebo. 5

So, guidelines provide no specific recommendations for statin therapy in the middle and oldest old without CVD. Despite the lack of information, approximately 39% of patients 79 and older are on statin therapy for primary prevention of cardiovascular events. 3

Because this population is known to be more vulnerable to adverse drug effects, we see hospitalizations due to statin-induced rhabdomyolysis is 5 times more likely in patients 65 and older versus younger patients.2 Even moderate muscle pain, a common side effect of statins, could cause already frail patients to increase their fall risk and/or immobility. And in rare cases, statins cause confusion and memory loss, especially with atorvastatin, lovastatin, simvastatin. Fortunately, these effects are reversible upon discontinuation.6, 7

More research of statin benefits vs. risks, specifically in patients 75 and older at risk for CVD, are needed. So for now, patient-centered decision-making is key when the evidence is unclear.

Current ACC/AHA guidelines recommend that in patients >75 with established CVD

  • Begin statin therapy, but at a moderate intensity. There is strong evidence of statin cardiovascular benefit in this population.
  • In patients already well established on a high intensity statin with no complications, this may be continued. 8

In patients > 75 without established cardiovascular disease:

  • The decision to initiate a statin should be individualized and should weigh in heavily on patient concerns and goals. 2
    • Factors that may support initiation of a statin:
      • Few comorbidities,
      • > 1 cardiovascular risk present
      • Patient priority to minimize cardiovascular risk
    • Factors that may support avoiding statin initiation:
      • High comorbidities
      • Only 1 cardiovascular risk present
      • History of myopathy
      • Severe dementia
      • Frailty
      • High risk of drug-drug interactions
      • Patient priority to avoid pill burden
      • Patient priority to avoid adverse drug effects
      • Life expectancy < 1 year
  • In patients already well established on a statin with no complications, this may be continued.

Finally, in all elderly patients initiated on a statin, monitoring for adverse side effects should be a priority due to increased risks. Reassessment of factors such as development of dementia, frailty, and life expectancy should be made after starting therapy as these may change overtime and affect the decision to continue.

 

References:

  1. Ross SD, Allen IE, Connelly JE, Korenblat BM, Smith ME, Bishop D, Luo D. Clinical Outcomes in Statin Treatment TrialsA Meta-analysis. Arch Intern Med.1999;159(15):1793–1802. doi:10.1001/archinte.159.15.1793
  2. Pletcher, M. J., Coxson, P. G., Thekkethala, D., Guzman, D., Heller, D., Goldman, L., & Bibbins-Domingo, K. Statins for Primary Prevention in Older Adults.
  3. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1-45.
  4. ALLHAT Officers and Coordinators for the ALLHAT Col- laborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs. usual care: the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALL- HAT-LLT). JAMA 2002; 288: 2998–3007.
  5. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in eld- erly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–1630.
  6. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet2010;376:1670-81.
  7. Haag MD, Hofman A, Koudstaal PJ, et al. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry 2009;80:13-7.
  8. Lambert, M. (2014). ACC/AHA Release Updated Guideline on the Treatment of Blood Cholesterol to Reduce ASCVD Risk. American family physician90(4), 260.