Primary Prevention Statins Cut Mortality Even in the Very Elderly: VHA Study

Debra L. Beck

July 09, 2020

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that "age on its own shouldn't be a criterion not to use these drugs," Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, told theheart.org | Medscape Cardiology.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, Orkaby, VA Boston Healthcare System and Harvard Medical School, Boston, explained when interviewed.

"From available data, we don't really expect statins to start providing benefit in primary prevention until they've been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally," Orkaby said.

"But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years" of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were 75 years or older, write Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, observe Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, Australia, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, North Carolina, in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they write, "provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals."

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University School of Medicine, St. Louis, Missouri, who was not involved in the study but has previously worked with Orkaby, praised the analysis when speaking to theheart.org / Medscape Cardiology.

"It's one of the best studies I've seen addressing this particular issue. It's a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events."

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population — mostly white, male veterans — is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they write.

Rich said that the trial, although not a "slam dunk," has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

"This doesn't mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 — the type of people in this study — but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin."

There are two ongoing trials that may provide greater clarity, the authors observe. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they write. "While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study."

Orkaby had no disclosures; potential conflicts for the other authors are in the report. Rich reports having no conflicts of interest. Nicholls discloses receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Nelson had no disclosures.

JAMA. 2020;324:68-78, 45-46. Article, Editorial

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