Statin initiation may lower mortality risk in older veterans
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Statin initiation in older U.S. veterans free from atherosclerotic CVD at baseline reduced the risk for CV and all-cause mortality, researchers found in a retrospective cohort study.
“In this retrospective analysis, we found that the risk of dying from any cause was lower by 25% among veterans who were newly prescribed a statin compared with those who were not treated with statins,” Ariela R. Orkaby, MD, MPH, geriatrician and researcher at the VA Boston Health Care System and in the division of aging at Brigham and Women’s Hospital and Harvard Medical School, told Healio. “The risk of dying from a cardiovascular event such as a heart attack or stroke was lower by 20%. Secondarily, the risk of an overall cardiovascular event, including heart attacks, strokes, coronary bypass surgery or coronary catheterization, was 8% lower in those prescribed a statin compared with those who were not prescribed a statin.”
Older patients without ASCVD
In this study published in JAMA, researchers analyzed data from 326,981 patients (mean age, 81 years; 97% men) aged 75 years and older who regularly used U.S. Veterans Affairs services between 2002 and 2012. All patients were free from ASCVD at baseline, defined as a history of transient ischemic attack or stroke, MI, coronary revascularization or peripheral vascular disease. No patients were taking statins at entry into the cohort but were monitored for initiation throughout the study.
The primary outcomes for this study were CV and all-cause mortality. Secondary outcomes included ischemic stroke, MI, revascularization and a composite of these ASCVD events.
From baseline, new statin users accounted for 17.5% of the patient population in this study.
There were 206,902 deaths including 53,296 CV deaths during a mean follow-up of 6.8 years. This equaled to 78.7 total deaths per 1,000 person-years in patients taking statins compared with 98.2 total deaths per 1,000 person-years in those not taking statins before adjustment (weighted incidence rate difference per 1,000 person-years, 19.5; 95% CI, 20.4 to 18.5). For CV deaths, there were 22.6 deaths per 1,000 person-years in the statin group vs. 25.7 deaths per 1,000 person-years in the nonstatin group (weighted incidence rate difference per 1,000 person-years, 3.1; 95% CI, 3.6 to 2.6).
During follow-up, there were 123,379 composite ASCVD events. This equated to 66.3 events per 1,000 person-years in patients taking statins compared with 70.4 events per 1,000 person-years in those not taking the medications (weighted incidence rate difference per 1,000 person-years, 4.1; 95% CI, 5.1 to 3).
Researchers applied propensity score overlap weighting to this data, which showed that statin use was significantly linked to a lower risk for CV death (HR = 0.8; 95% CI, 0.78-0.81) and all-cause mortality (HR = 0.75; 95% CI, 0.74-0.76) when compared with those not taking statins. The HR for a composite of ASCVD events was 0.92 when comparing these two groups (95% CI, 0.91-0.94).
“Age alone should not be a reason not to prescribe a statin to older adults,” Orkaby said in an interview.
Orkaby added that more research is needed in this area. She said, “Although real-world, carefully conducted epidemiologic studies like this one are very useful to further our understanding of the role of statins for cardiovascular prevention, we still need clinical trials, the gold standard of evidence. An exciting new trial called PREVENTABLE will soon begin enrolling participants [aged at least 75 years] across the U.S. to help us further understand the role of statins in this age group.”
‘Fastest-growing population subgroups’
In a related editorial, Stephen J. Nicholls, MBBS, PhD, director of Monash Heart and professor at Monash University in Melbourne, Australia, and Adam J. Nelson, MBBS, PhD, postdoctoral cardiology fellow at Duke Clinical Research Institute, North Carolina, wrote: “The findings of the study by Orkaby et al provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals. 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. Because patients older than 75 years represent one of the fastest-growing population subgroups in health care systems, there is a major need to provide an evidence base that informs use of therapies that are both safe and efficacious, in a cost-effective manner.”
Reference:
For more information:
Ariela R. Orkaby, MD, MPH, can be reached at aorkaby@bwh.harvard.edu; Twitter: @drarorkaby.
Perspective
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Udho Thadani, MD, MRCP, FRCPC, FACC, FAHA, FCCS
American life expectancy is likely to increase to well beyond 75 years with time, and even at age 75 years, women currently outlive men by more than 3 years. Thus, it is critical to keep these older patients healthy and prevent or at least reduce the number of serious CV events such as MI and stroke which they might experience over time.
This is currently being achieved with not only lifestyle changes, including abstinence of smoking, but also with adequate control of BP and diabetes. In addition, physicians are reminded to routinely use statins in the elderly at high risk, as stains have been proven safe and effective for primary prevention of ASCVD in the younger population who are at increased risk for these events. However, there is lack of good evidence to support the routine use of high-dose statins in the elderly for primary prevention of ASCVD. Guidelines recommend high-dose potent statins, and this is based on subgroup analysis of data in the elderly from multiple outcome trials of all age groups. In the elderly, the negative effect of statins on the cognitive function and mobility due to muscle pains remains a constant concern.
The retrospective study by Orkaby and colleagues concludes that in 57,178 veterans who initiated statin therapy between 2000 and 2012, statin use was associated with significantly lower all-cause and CV mortality, but had no effect on nonfatal MI or stroke. Absolute reduction in CV mortality was 3.1%, and this benefit was not associated with any increase in major adverse effects from statin therapy.
Although these results on CV mortality reduction are reassuring, one must realize that this was not a randomized trial, and despite a propensity-matched analysis, unknown confounders could have influenced the result. What is surprising is that there was no reduction in nonfatal MI and stroke rates with statin therapy, as has been shown with statin trials in the younger population and subgroup analysis in the elderly.
The safety profile of low-dose and weak statins in this study is reassuring but cannot be claimed for use of high-dose statins in the elderly. Furthermore, these results are only applicable to male veterans, who comprised more than 97% of the participants studied. Larger adequately powered studies in the elderly of both genders and different racial backgrounds are needed to make definite recommendations of the use of high-dose, potent statins in older people for primary prevention.
From the results of this trial and subgroup analysis of previous trials with high-dose, potent statins in the elderly, one can safely recommend to start a low dose of a potent statin and increase the dose as tolerated but without any adverse effects, which could impair the quality of life.
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