In the JournalsPerspective

Statins may not affect outcomes in older patients without diabetes, CVD

In a retrospective cohort study of adults aged 75 years or older without prior CVD, statin use did not reduce risk for CVD or all-cause mortality in those without diabetes.

Among patients with diabetes, statins were associated with reduced CVD and mortality risk in those aged 75 to 84 years, but not in those aged 85 years or older.

The researchers identified 46,864 individuals from the Catalan primary care system database who were aged 75 years or older (mean age, 77 years; 63% women) between 2006 and 2015 and did not have clinically recognized atherosclerotic CVD. Participants were stratified by age (75-84 years; 85 years), presence or absence of diabetes, and statin use. Median follow-up was 5.6 years.

Among those without diabetes, there was no significant difference between statin use and nonuse in risk for atherosclerotic CVD in either age group (aged 75-84 years: HR = 0.94; 95% CI, 0.86-1.04; aged 85 years: HR = 0.93; 95% CI, 0.82-1.06) and in risk for mortality in either age group (aged 75-84 years: HR = 0.98; 95% CI, 0.91-1.05; aged 85 years: HR = 0.97; 95% CI, 0.9-1.05), Rafel Ramos, MD, PhD, from Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Catalonia, Spain, and colleagues wrote.

However, in those with diabetes aged 75 to 84 years, statin use conferred reduced risk for atherosclerotic CVD (HR = 0.76; 95% CI, 0.65-0.89) and mortality (HR = 0.84; 95% CI, 0.75-0.94), according to the researchers. The trends were not present in those with diabetes aged 85 years or older (HR for CVD = 0.82; 95% CI, 0.53-1.26; HR for all-cause mortality = 1.05; 95% CI, 0.86-1.28).

In participants with diabetes, statins showed a protective effect against atherosclerotic CVD and all-cause mortality; this effect was substantially reduced beyond the age of 85 years and disappeared in nonagenarians,” Ramos and colleagues wrote.

In a related editorial, Aidan Ryan, academic clinical fellow in metabolic medicine from the department of laboratory medicine, University Hospital Southampton, United Kingdom, and colleagues wrote: “If in the process of shared decision-making, older patients express a preference for extending longevity, then current evidence supporting statins for primary prevention remains limited. A patient preference for reduction in myocardial infarction or stroke, however, might help to tilt the balance in favor of statin prescription but the absolute risk reduction, number needed to treat to prevent a CVD event in older patients remains uncertain.” – by Erik Swain

Disclosures: The study and editorial authors report no relevant financial disclosures.

In a retrospective cohort study of adults aged 75 years or older without prior CVD, statin use did not reduce risk for CVD or all-cause mortality in those without diabetes.

Among patients with diabetes, statins were associated with reduced CVD and mortality risk in those aged 75 to 84 years, but not in those aged 85 years or older.

The researchers identified 46,864 individuals from the Catalan primary care system database who were aged 75 years or older (mean age, 77 years; 63% women) between 2006 and 2015 and did not have clinically recognized atherosclerotic CVD. Participants were stratified by age (75-84 years; 85 years), presence or absence of diabetes, and statin use. Median follow-up was 5.6 years.

Among those without diabetes, there was no significant difference between statin use and nonuse in risk for atherosclerotic CVD in either age group (aged 75-84 years: HR = 0.94; 95% CI, 0.86-1.04; aged 85 years: HR = 0.93; 95% CI, 0.82-1.06) and in risk for mortality in either age group (aged 75-84 years: HR = 0.98; 95% CI, 0.91-1.05; aged 85 years: HR = 0.97; 95% CI, 0.9-1.05), Rafel Ramos, MD, PhD, from Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Catalonia, Spain, and colleagues wrote.

However, in those with diabetes aged 75 to 84 years, statin use conferred reduced risk for atherosclerotic CVD (HR = 0.76; 95% CI, 0.65-0.89) and mortality (HR = 0.84; 95% CI, 0.75-0.94), according to the researchers. The trends were not present in those with diabetes aged 85 years or older (HR for CVD = 0.82; 95% CI, 0.53-1.26; HR for all-cause mortality = 1.05; 95% CI, 0.86-1.28).

In participants with diabetes, statins showed a protective effect against atherosclerotic CVD and all-cause mortality; this effect was substantially reduced beyond the age of 85 years and disappeared in nonagenarians,” Ramos and colleagues wrote.

In a related editorial, Aidan Ryan, academic clinical fellow in metabolic medicine from the department of laboratory medicine, University Hospital Southampton, United Kingdom, and colleagues wrote: “If in the process of shared decision-making, older patients express a preference for extending longevity, then current evidence supporting statins for primary prevention remains limited. A patient preference for reduction in myocardial infarction or stroke, however, might help to tilt the balance in favor of statin prescription but the absolute risk reduction, number needed to treat to prevent a CVD event in older patients remains uncertain.” – by Erik Swain

Disclosures: The study and editorial authors report no relevant financial disclosures.

    Perspective
    Daniel E. Forman

    Daniel E. Forman

    As the study asserts, the rationale for treating with statins as primary prevention is highly compelling in older adults, as aging itself is associated with high CV risk, and thus, statins seem a reasonable consideration. Nonetheless, there has been a lack of research regarding statins in the very old population (ie, adults aged 75 years or older). Ironically, many trials have specifically avoided enrolling very old adults precisely because they are so susceptible to age-related multimorbidity, polypharmacy, frailty and other complexities. Thus, there is a dearth of data pertaining to patients who are especially vulnerable to the diseases for which treatment is indicated and for which the study should be prioritized. 

    Therefore, this study is important as it tries to focus on the issue, and it is especially important as it focuses on very old adults with diabetes. Diabetes is an important dimension of the work as older adults are especially susceptible to it, and diabetes adds to CV risk, so the best care of diabetes is a priority. Treating elevated glucose aggressively in older adults with diabetes has not been shown to be effective, so understanding what is effective is particularly valuable for clinicians.

    Diabetes adds to CV risk, and therefore treating with statins as primary prevention in a population with diabetes is very logical. It was a reasonable expectation that those with diabetes would benefit disproportionately, and it seems they did. 

    This study reinforces rationale to treat with statins in very old adults with diabetes with data that seem quite compelling through age 85. This makes sense conceptually.

    The study falls short of saying anything with certainty regarding adults without diabetes. In other words, despite the fact the authors make the assertion that there was no benefit in those who did not have diabetes, this statement is flawed. First, there may be many other subsets of adults who benefit more than others that were not considered in this investigation. For example, it is known that patients with high calcium deposits in their hearts may benefit from primary statin prevention more than others; however, this study did not delineate differences among adults with this well-known index of added risk discrimination. It also did not consider the utility of higher doses of statins. The fact is that a higher dose of a statin may have more treatment benefit, but many older adults are only administered very low doses. For these and many other reasons, it is not accurate to say that statins only bring about benefit in those with diabetes, and/or that there are age cutoffs when treatment is no longer effective.

    The fact remains, statins are not a panacea. There are compelling reasons to consider using them, but also reasons to consider not using them. On the “pro” side, they reduce CV events. Perhaps this can lower mortality, but even more important to many older adults is that they can reduce strokes and hospitalizations. Some data (in other studies) suggest they increase function and decrease frailty, which is a very important consideration for older adults. On the “con” side, statins add to risks of polypharmacy, they add to burden of cost, and they can cause myalgias. Some people assert they can add to confusion. Each aspect of the pros and cons remains somewhat controversial.

    The NIH just released a plan to study primary prevention of statins in older adults. It is seen as an issue that needs much more study and insight than this retrospective cohort study can provide.

    The authors emphasize a recent study that showed no benefit of primary statin therapy (Han BH, et al. JAMA Intern Med. 2017;doi:10.1001/jamainternmed.2017.1442), but that was a study based on data from the much older ALLHAT-LLT trial, which many have considered as an inherently flawed trial in that it was trying to analyze benefits of a relatively weak statin (pravastatin) when many of the people in the control arm ended up taking newer, more potent statins (particularly simvastatin) that were released during the time the study was in effect. Thus, the publication by Han and colleagues has been severely criticized.    

    Notably, another recent study not mentioned in this publication (Orkaby AR, et al. J Am Geriatr Soc. 2017;doi:10.1111/jgs.14993) did show benefit. This is exactly why the NIH is investing so much money to now study the issue more definitively.

    • Daniel E. Forman, MD
    • Chair, Section of Geriatric Cardiology
      UPMC Heart and Vascular Institute

    Disclosures: Forman reports no relevant financial disclosures.