Advanced Age and CV Risk: To Start or Not to Start a Statin in Older Patients?

Definition of Elderly^[1,2]

• Patients are living longer and longer
• The high proportion of cardiovascular disease (CVD) in the elderly is a huge problem

The Elderly and Vascular Disease^[2,31]

• Many comorbidities associated with older age, including CVD, renal disease, chronic obstructive pulmonary disease (COPD)
• Focus for patients in 40s and 50s is myocardial infarction (MI); stroke becomes more important in the elderly
• Prevention is clear (lifestyle modification, smoking cessation, etc), but risk factor reduction is less clear
• Many question whether low-density lipoprotein (LDL) reduction, statin therapy are worthwhile in the elderly
• HYVET trial clarified the benefit of treating hypertension in persons ≥80 years of age

Tailoring Lipid-Lowering Therapy in the Elderly

Statins: Highly Favorable Risk-Benefit Ratio^[3]

• Elderly patients often have muscle aches and pains, and may attribute them to therapy and stop taking their statin
• In every age category, there are small risks associated with statin therapy
• Cases of cognitive dysfunction have been reported in observational studies, but not in randomized controlled trials
• Potential side effects cause concern in the patient

Highest Risk of Statin Toxicity^[4,5]

• Elderly are more prone to adverse events (AEs), and the likelihood of AEs should be evaluated before starting statins
• Physiology starts to change after 80 years, so extra caution is warranted
• These precautions apply to other drugs as well, not only to statins
• Polypharmacy refers to prescription and over-the-counter medications
  • Elderly are heavy users of over-the-counter medications
  • It is not known how supplements, over-the-counter agents interact with statins

Polypharmacy and Drug-Drug Interactions^[2,6]

• In younger patients, high-dose simvastatin should not be used with calcium antagonists

Statin Pharmacokinetics^[7]

• Statins efficacious as a group, but have very different pharmacokinetics individually

Pitavastatin and Pravastatin: Less Likely to Interact With Common Medications in CV Care^[8]

• Statin treatments are lifelong, and a patient in their 80s may live another 5 to 10 years
• Patients on statins should not be given macrolide antibiotics for a chest infection
• Many medications cause dehydration

Common Drug Interactions With Statins^[4]

• Some newer oral anticoagulants can increase statin levels
• Physicians tend to focus on the immediate problem, and patients will not remember every potential medication issue
• Approach to choosing a statin: follow guidelines, start with low dose, and choose a statin not likely to have drug-drug interactions
• Patient education handouts listing medications to beware of are useful
• Physician education on co-prescribing is important
• Pharmacists, nurses, and other healthcare professionals play an important role in preventing drug-drug interactions

PROSPER: Study Design^[9]

PROSPER: Primary Endpoint^[9]

• Secondary prevention group benefited, as expected in a high-risk, elderly population
• PROSPER trial is powered on overall treatment effect
• About half the patients were primary prevention with a lower event rate, not expected to be statistically significant

Primary Prevention in the Elderly: MI and Stroke Reduced With Statins^[10,32]

• There is a clear case for primary prevention using statins in patients with established CVD, regardless of age, unless there is good reason not to use it
• The argument against primary prevention in elderly individuals with no cardiovascular (CV) events discounts short-term risk
• Primary prevention trials that showed no all-cause mortality benefit, like WOSCOPS, have been criticized
  • Over 3 years of follow-up, competing risks from infections, cancer deaths
  • Trends for CV mortality reduction are seen when strokes are reduced

JUPITER and HOPE-3 Trials^[11-13]

• Annualized event rate threshold was once 2% per year for statins
• These contemporary trials show clear benefit of statins
• Number needed to treat (NNT) relatively small compared with other studies because absolute risk is so high

STAREE: STAtins for Reducing Events in the Elderly^[9,11,14]

• The STAREE trial is enrolling in Australasia and will recruit in Europe
• STAREE is using a more potent statin dose and a more modern statin than used in PROSPER, thus a bigger treatment effect is expected
• The answers on primary prevention will not necessarily come from any 1 study
• STAREE could be for primary prevention in the elderly what JUPITER (n=6801)was for primary prevention in women

Secondary Prevention^[9,15]

Secondary Prevention (cont)^[16-21]

• PROVE-IT was conducted when people were still arguing about treatment goals
• National Cholesterol Education Program (NCEP) low-density lipoprotein cholesterol (LDL-C) goal: 70 mg/dL
• To choose the right therapy for this high-risk patient group, due consideration must be given to the different treatments, safety, and the reason for treatment

CTT Meta-Analysis^[22]

• Cholesterol Treatment Trialists' (CTT) Collaboration meta-analysis showed similar benefit, safety for ages ≤65, >65 to ≤75, and >75 years
• Physicians should reassure patients that side effects are not permanent, can be relieved by dose reduction or switching to another statin

Guideline Recommendations: Statin Therapy in the Elderly (>75 years)^[23,24,33]

• European Joint National Committee (JNC) hypertension guidelines defined older populations differently, resulting in under-treatment in certain regions
• US guidelines do not recommend an LDL-C treatment target
• European guidelines do not distinguish elderly from general population, suggest treatment targets based on risk
  • LDL-C <70 mg/dL for very high risk
  • LDL-C <100 mg/dL for high risk

SCORE: Cardiovascular Disease Risk Estimation^[24-26]

• European guidelines have taken into account all evidence, not only randomized trials, as patients do not always fit into randomized trials
• Treatment goals benefit patients and physicians
• LDL-C <70 mg/dL should be the goal for patients with atherosclerotic vascular disease

REAL CAD Primary Endpoint: CV Death/MI/Ischemic Stroke/Unstable Angina^{[23-25,27,34]}

• Primary prevention is a challenge, and approaches differ in the US and Europe
  • Risk prediction by Pooled Cohort Equations in US, SCORE in Europe
  • US guidelines: no recommendation for primary prevention >75 years of age
  • European guidelines: number of risk factors, not age, determines therapy
• Statins work, and every statin tested has a positive outcome trial in this patient group

Nonadherence Is a Risk Factor for CV Events^[28,29]

Reassuring the Patient About Statins

• The team-based approach is extremely important

2015 ACC Health Policy Statement: Team Management^[30]

• Pharmacists can call the physician's attention to polypharmacy
• The only way to success is to work together with the care team and the patient

Conclusion

Thank You

This content has been condensed for improved clarity.