Lower cardiovascular death, revascularization in veterans

Primary prevention with a statin in elderly military veterans reduced all-cause and cardiovascular mortality, a retrospective study using Veterans Health Administration (VHA) data found.

Compared with propensity-matched non-statin users, veterans age 75 and over who started a statin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) demonstrated lower risk of all-cause mortality (HR 0.75, 95% CI 0.74-76) and cardiovascular death (HR 0.80, 95% CI 0.78-0.81) over a mean followup of about 7 years.

Results were consistent even in people with advanced age or comorbidities, with similar risks for people 90 and older or with dementia, reported Ariela Orkaby, MD, MPH, of the VA Boston Healthcare System and coauthors in JAMA. “Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD,” they wrote.

The findings “support the VHA 2014 cholesterol guidelines, which did not have a cutoff for age for primary prevention, and the updated American Heart Association/American College of Cardiology 2018 recommendation to consider prescribing statins to those 75 years and older,” they added.

“These findings provide a compelling argument for use of statins for primary prevention in older patients,” noted Stephen Nicholls, MBBS, PhD, of Monash University in Australia, and Adam Nelson, MBBS, PhD, of Duke University in Durham, North Carolina, in an accompanying editorial. They “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals,” they added.

Increasing numbers of older patients who might benefit from ASCVD risk reduction therapy are relatively underrepresented in clinical trial data: patients older than 75 made up 8% of trial participants in 28 statin trials.

Conflicting data from underpowered subgroup analyses and limited observational studies is reflected in diverging ASCVD risk prevention guidelines.

Orkaby and colleagues used data from the VHA for patients with a clinical visit in 2002-2012 with follow-up through December 2016. A new-user design excluded those with prior statin use and propensity matching balanced the likelihood that comparison groups — started or did not start a statin during followup — had similar chances of being prescribed a statin. Researchers included 326,981 patients; 91% were white, 97% were men, and mean age was 81.

During mean followup of 6.8 years, 57,178 (17.5%) started a statin based on receiving a prescription, most commonly simvastatin. New statin users were more likely to have hyperlipidemia, hypertension, and diabetes, as well as arthritis and polypharmacy, but less likely to have dementia.

Overall mortality was 78.7 and 98.2 total deaths/1,000 person-years among statin users and nonusers, respectively (weighted incidence rate difference (IRD)/1,000 person-years –19.5, 95% CI –20.4 to –18.5).

Cardiovascular deaths were 22.6 and 25.7 per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1,000 person-years –3.1, 95% CI –3.6 to –2.6).

For a composite nonfatal ASCVD event secondary outcome, the hazard ratio was 0.92 (95% CI 0.91-0.94) favoring statin use. Of the composite’s components — myocardial infarction (MI), ischemic stroke, and revascularization — only reduced revascularization was significant. HRs were 0.99 (95% CI 0.97-1.03) for MI, 0.98 (95% CI 0.96-1.01) for ischemic stroke, and 0.89 (95% CI 0.88-0.91) for revascularization.

Sensitivity analysis for risk at 2-year intervals showed that statin treatment was associated with lower mortality in the first three 2-year intervals. All-cause mortality HRs at 2, 4, and 6 years were 0.68, 0.79, and 0.87, respectively.

“In this study, a 25% relative reduction in all-cause mortality was observed in new statin users,” the editorialists wrote. “This magnitude of benefit was nearly 3 times greater than that reported in meta-analyses of statin trials and also was apparent early, with evidence of a 32% reduction in mortality within the first 2 years.”

“In addition, the benefits on both mortality and coronary revascularization were not accompanied by a reduction in either myocardial infarction or ischemic stroke,” they continued. “Whether these findings reflect evidence of residual confounding, chance, or a true biological effect requires further investigation.”

“While randomized trials will provide the most definitive data to support these recommendations, observational data from large cohorts have the potential to guide clinical practice in the interim,” they concluded.

The study did not account for adverse effects of statins or the role of possible discontinuation. Other limitations include lack of generalizability, as the cohort was largely male and white. Residual confounding may have persisted and claims data may have been inaccurate or incomplete. In addition, simvastatin was used most commonly in this study, which does not reflect current practice.

  1. Primary prevention with a statin in elderly military veterans reduced all-cause and cardiovascular mortality.

  2. Findings were based on a retrospective study using Veterans Health Administration (VHA) data. Clinical trials are needed to determine the role of statin therapy in older adults, the researchers said.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This research was supported by awards from the VA and the National Institute on Aging.

Orkaby had no disclosures.

Nicholls reported receiving a Principal Research Fellowship from the National Health and Medical Research Council of Australia; research support from AstraZeneca, Amgen Inc, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and consulting fees and honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Nelson reported no disclosures.

Cat ID: 102

Topic ID: 74,102,282,494,102,4,914,192,255,925