Primary Prevention Statins in Older Adults: Personalized Care for a Heterogeneous Population

Deirdre O'Neill, MD, MSc; Neil J. Stone, MD; Daniel E. Forman, MD

Disclosures

J Am Geriatr Soc. 2020;68(3):467-473. 

In This Article

Case Study 3

Patient C.W., a thin 80-year old woman, presents to clinic in a wheelchair pushed by her husband. She has a past medical history of moderate to severe aortic stenosis, hypertension, hyperlipidemia, malnutrition, mild dementia, chronic kidney disease with baseline creatinine 2.0, osteoporosis, and urinary incontinence. She resides in an assisted living facility and as per her husband, C.W. has been becoming "weaker" over the past year. She ambulates with a walker for short distances, using a wheelchair any time she leaves her apartment. She is dependent in all instrumental ADLs. She admits to being very sedentary, particularly in the past year, due to progressive fatigue and weakness, without myalgias. She has had one fall in the past year, without injury.

C.W. is currently on ramipril 5 mg/day, atorvastatin 40 mg/day, donepezil 10 mg/day, oxybutynin 10 mg/day, vitamin B12 1000 μg/day, ferrous sulfate 325 mg/day, and alendronate 70 mg/week. Blood pressure is 138/72, HR 70 bpm and regular. She is clinically euvolemic. She has no focal weakness or neurologic deficits. However, when asked to do five chair rises, she is unable to do even one. Her gait, with the use of her walker, is slow, with a calculated gait speed of .6 m/s. Laboratory values include hemoglobin 10.8, hematocrit 32, white blood count5.2, platelets 360, sodium 138, potassium 3.8, creatinine 2.1, HbA1c 5.5%, total cholesterol 220 mg/dL, LDL-C 130 mg/dL, HDL-C 40 mg/dL, triglycerides 150 mg/dL, and creatine kinase 100.

When asked about her goals and what is important to her, the patient states that she likes to go out for dinner once a week with her husband and that she wishes she could do so with her walker, rather than her wheelchair. She also wants to avoid a nursing home level of care because she enjoys her current assisted living facility, especially the friends she has made there.

Case 3 Summary & Discussion

C.W. is an older frail disabled woman who values function and quality of life amid a slow general decline in her health. The case study describes a woman of similar chronological age as the previous two case studies but with significantly more frailty and disability, demonstrating the wide clinical variability among older adults of similar chronological age. The progressive clinical declines are likely exacerbated by sarcopenia, raising particular concerns about putative risks of myalgias and statin-related myopathy, particularly in an older adult on a high-potency primary prevention statin. Clearly, further data on benefits and adverse effects in this kind of older patient are needed to aid decision making.

Although rhabdomyolysis with statin therapy is rare, statins are not infrequently associated with disproportionate weakening, pain, and functional impairment, with a reported incidence of myalgias in the literature varying from only 1% to as high as 25%.[47] Krishnan and Thompson reviewed six studies. Although they found insufficient data for a causal relationship between statins and muscle weakness, they indicate a suggestion of statin-associated muscle weakening, particularly in older adults.[48]

Statin discontinuation is an important consideration in patients with frailty and physical decline, and also in adults with any end-stage disease and a palliative approach to care. In contrast, statins are often continued in patients with limited life expectancies. In one study, 31% of those with cancer filled a prescription for a statin within 30 days of their death.[49] Statin discontinuation in palliative patients was demonstrated to be beneficial. Kutner et al showed that statin de-prescription in adults with an estimated life expectancy of 1 month to 1 year was associated with improved quality of life, use of fewer non-statin medications and reduced medication costs, without an increase in CV events of 60-day mortality.[50] However, such a rationale to remove statins should also be counterbalanced by literature suggesting that physicians' predictions of life expectancy are fraught with inaccuracy,[51] with the implicit concern that removing statins could be premature and potentially detrimental.

C.W. describes optimized function as her primary medical priority. This case study patient does not describe typical myalgias or have an elevated creatinine kinase level suggestive of myopathy,[46] but subtle manifestations of muscle pain or weakening associated with statins have been described. Golomb et al performed a randomized controlled trial of primary prevention statin (pravastatin or simvastatin) vs placebo, demonstrating that both simvastatin and pravastatin were significantly associated with self-reported reduced energy and fatigue, disproportionately affecting women.[52] Dobkin showed that when serial muscle strength testing was performed on patients taking a statin, it was not uncommon for muscle weakness to be evident without associated laboratory abnormalities, and that it was fully reversible 3 months after the statins were discontinued.[53]

Thus in an older adult on primary prevention statin who is experiencing functionally limiting fatigue and weakness, statin de-prescribing may be reasonable, especially in those who are frail. One option is to do a de-challenge-re-challenge test. In this situation, a patient would stop the statin for 3 weeks and then re-challenge with a statin. Ideally, after a few weeks, the patient can appreciate if stopping the statin causes the symptoms to remit. Re-challenging with statin 3 weeks later allows the patient to determine whether or not their symptoms return. Management options include trying a lower dose statin, changing to an alternative statin, or consideration of statin discontinuation.

The decision to discontinue a statin is not without risk. In a recent population-based cohort study by Giral et al in more than 120 000 patients older than 75 years on primary prevention statin, statin discontinuation (occurring in 14.3%) was associated with a 33% increased risk of a CV event.[54] Overall, risks and benefits of statins should be continuously reassessed in the context of dynamic changes in each patient's disease burdens, functional changes, prognosis, and goals of treatment.

Finally, It should not be simply assumed that all frail adults want to forgo their statins. One study stands out in showing that some older frail adults prefer to stay on statins precisely because they are frail,[55] highlighting the importance of patient autonomy. This finding again underscores the need for shared decision making both in the use and/or discontinuation of statins.

Once again, a CAC score could be used in this case to assist in the decision to discontinue statin. If the patient was unsure of her desire to stop statin therapy, a CAC score of 0 could be helpful in informing a shared decision-making process. However, if the patient was functionally impaired, as in the case of C.W., and willing to trial statin de-prescription, no particular CAC score would mandate continuation of a statin when potential adverse effects could be worsening function and quality of life.

In conclusion, the 2018 AHA/ACC cholesterol guidelines expanded on the previous 2013 guidelines, providing additional data and insights on the management of hypercholesterolemia. However, due to limited evidence of statin benefits in older adults, primary prevention statin use in those older than 75 years remains only a IIb indication. Our review highlights that because a IIb recommendation is inherently "weak" and calls for additional data as well as a need for tailored care, responding to each patient's particular circumstances. The three case scenarios illustrate such complexity and the value of a shared decision process.

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