Statins for Primary Prevention of Cardiovascular Events and Mortality in Older Men

Ariela R. Orkaby, MD, MPH; J. Michael Gaziano, MD, MPH; Luc Djousse, MD, ScD; Jane A. Driver, MD, MPH

Disclosures

J Am Geriatr Soc. 2017;65(11):2362-2368. 

In This Article

Abstract and Introduction

Abstract

Background/Objectives We sought to determine whether statin use for primary prevention is associated with a lower risk of cardiovascular events or mortality in older men.

Design Prospective cohort study.

Setting Physicians' Health Study participants.

Participants 7,213 male physicians ≥70 years without a history of cardiovascular disease (CVD).

Measurements Multivariable propensity score for statin use with greedy matching (1:1) to minimize confounding by indication.

Results Median baseline age was 77 (70–102), median follow-up was 7 years. Non-users were matched to 1,130 statin users. Statin use was associated with an 18% lower risk of all-cause mortality, HR 0.82 (95% CI 0.69–0.98) and non-significant lower risk of CVD events, HR 0.86 (95% CI 0.70–1.06) and stroke, HR 0.70 (95% CI 0.45–1.09). In subgroup analyses, results did not change according to age group at baseline (70–76 or >76 years) or functional status. There was a suggestion that those >76 at baseline did not benefit from statins for mortality, HR 1.14 (95% CI 0.89–1.47), compared to those 70–76 at baseline, HR 0.83 (95% CI 0.61–1.11); however the CIs overlap between the two groups, suggesting no difference. Statin users with elevated total cholesterol had fewer major CVD events than non-users, HR 0.68 (95% CI 0.50–0.94) and HR 1.43 (95% CI 0.99–2.07)), respectively.

Conclusions Statin use was associated with a significant lower risk of mortality in older male physicians ≥70 and a nonsignificant lower risk of CVD events. Results did not change in those who were >76 years at baseline or according to functional status. There was a suggestion that those with elevated total cholesterol may benefit. Further work is needed to determine which older individuals will benefit from statins as primary prevention.

Introduction

Guidelines suggest there is limited evidence to recommend statins for primary prevention of cardiovascular disease (CVD) in adults >75 years.[1,2] This may be a direct result of excluding older individuals, particularly those with multimorbidity, from randomized trials.[3] However, prescriptions for statins for individuals >70 has increased significantly in the last two decades.[4] In 2008, 40% of the Medicare population was prescribed a statin.[5] In 2011, 12.5 million Medicare beneficiaries were >80,[6] amounting to a significant investment of resources for a drug for which there is as yet no clear evidence of benefit in the oldest and fastest growing segment of the population.[7]

Multiple primary and secondary prevention trials[8–13] demonstrated that statins reduce mortality and cardiovascular (CV) events in those <75 years. A meta-analysis of primary prevention statin trials in older adults (mean age 73) revealed a reduction in CV events, but not mortality.[14] Limited, conflicting evidence has generated significant debate,[15–17] and calls for additional trials.[18]

One challenge involves identifying older adults at increased CVD risk who might benefit from statins for primary prevention. Using the Pooled Cohort Risk Assessment Equation,[1] as recommended by cholesterol guidelines, white men >70 with optimal risk factors have a predicted 10-year risk of CVD of 15.7%. The guidelines suggest that those with an estimated risk >7.5% should be offered a statin. No specific recommendations are made for patients >75. Existing risk assessments, such as the Framingham risk score and the European SCORE were not developed in older cohorts and do not account for multimorbidity, function, frailty, or life limiting illnesses.[19]

Additionally, the older adult population has long had inconsistent prescription patterns for many medications, including under-prescription of statins.[20] This may reflect clinicians' hesitancy to use a drug with side effects and drug-drug interactions that has not been studied in the very old.[21] Thus, we sought to examine the relationship between statin use for primary prevention of major CV events and mortality in men >70, with particular attention to those >75 years in subgroup analysis.

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