High-intensity lipid lowering in the elderly population

High-intensity lipid lowering in the elderly population
David Bunch, PharmD, 
Smiley’s Family Medicine

Background:In 2016 the U.S. Preventive Services Task Force concluded that there is not sufficient evidence to weigh the benefits and harms of statin use for primary prevention in those 76 years and older. The new 2018 ACC/AHA cholesterol guidelines recommend that it is reasonable for patients greater than 75 years of age with clinical ASCVD to receive moderate or high-intensity statin therapy, which differs from their previous 2013 endorsement of only utilizing moderate-intensity statins in this population. Furthermore, the 2018 ACC/AHA guidelines provide a weak recommendation that in adults 75 years of age or older with an LDL-C level of 70 to 189 mg/dL, initiating a moderate-intensity statin may be reasonable. In contrast, the 2014 NICE guidelines recommend for people 85 years or older to consider atorvastatin 20 mg as statins may be of benefit in reducing the risk of non‑fatal myocardial infarction. The purpose of this article is to summarize the evidence for using statins in elderly patients.

Evidence: Statins for secondary prevention in the elderly have been well documented in trials such as the PROVE IT-TIMI 22, SAGE, SPARCL, and HPS trials. More specifically, the SAGE trial showed a decrease in all-cause mortality with high-intensity over moderate-intensity statin therapy in those 65-85 years old with coronary artery disease (0.33 [95% CI 0.13 - 0.83]).  The recent IMPROVE-IT study determined that adding ezetimibe to simvastatin therapy for secondary prevention resulted in lower rates of their primary endpoint (a composite of death due to cardiovascular disease, myocardial infarction, stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days) and showed the greatest absolute risk reduction of 8.7% for patients 75 years or older (0.80 [95% CI 0.70 - 0.90]) with no difference found in safety endpoints. 

In regards to primary prevention, a retrospective cohort study in Spain by Ramos et al. found that for those aged 75-84 years without diabetes or atherosclerotic disease there was no significant benefit with statin use in either athlerosclerotic CVD (0.94 [95% CI 0.86 - 1.04]) or all-cause mortality (0.98 [95% CI 0.90 - 1.05]). However, those with diabetes in this age group saw an improvement in both atherosclerotic CVD (0.76 [95% CI 0.65 - 0.89]) and all-cause mortality (0.84 [95% CI 0.75 - 0.94]). The JUPITER trial tested the effects of high-intensity statin therapy in primary prevention and found that in the population ≥70 years of age, a comparable 39% reduction in risk was found for the combined cardiovascular endpoint of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death (0.61 [95% CI 0.43–0.86). 

In regards to safety, the JUPITER trial showed no significant difference in muscle weakness, newly diagnosed cancer, or disorders of hematologic, gastrointestinal, hepatic, or renal systems. In this trial, the rates of myopathies were also similar between groups. These results are consistent with other studies such as the SPARCL trial, but slightly different from the HOPE-3 trial which found that more participants in the rosuvastatin group had muscle pain or weakness (5.8% vs. 4.7%, P=0.005).  

Discussion and Clinical Impact: As patients get older their risks for having a major cardiovascular event increase, but so do their frailty and risk of adverse events. The 2018 ACC/AHA guidelines provide clearer recommendations for those 75 years or older with clinical ASCVD or diabetes, and new evidence in this area suggests that the addition of ezetimibe to statin therapy in the secondary prevention group may have substantial benefit as well. However, the conversation becomes less clear in the area of primary prevention without diabetes. Studies with subgroup analyses on those over 70 years of age seem to show benefit, but meta-analyses with subgroup analyses of those over 75 years do not meet significance. The main concern for statin use is along the line of muscle pain and muscle weakness. Clinician’s unsure of the patient’s benefits can order a coronary artery calcium score to determine the patient’s actual risk as recommended by the 2018 ACC/AHA. If well tolerated, the benefits may outweigh the risks with statin use in the elderly. However, with the minimal evidence in this age group, each decision should be focused on the individual patient and their risks, frailty, and preferences for care. 

Abbreviations:

ACC/AHA - American College of Cardiology/American Heart Association

ASCVD - Atherosclertoic cardiovascular disease 

HOPE-3 - Health Outcomes Prevention Evaluation-3

HPS - Heart Protection Study 

IMPROVE-IT- IMProved Reduction of Outcomes: Vytorin Efficacy International Trial 

JUPITER - Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin

NICE - National Institute for Health and Care Excellence 

PROVE IT-TIMI 22 - The Pravastatin or Atorvastatin Evaluation and Infection Therapy - Thrombolysis in Myocardial Infarction 22 

SAGE - Study Assessing Goals in the Elderly 

SPARCL - Stroke Prevention by Aggressive Reduction in Cholesterol Levels 

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