From the Journals

Could some elderly skip statins based on negative risk markers?

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Actionable findings could limit pharmacotherapy overuse

This study suggests that atherosclerosis imaging tests are the strongest negative risk factors identified to date in cardiovascular medicine. The results are clinically actionable and should shape our approach to these tests in clinical practice.

Atherosclerosis imaging tests could be important in preventing overuse of pharmacotherapy for primary prevention in older adults, nearly all of whom would be considered at elevated risk by current standards.

Results for other candidate markers in the study were generally unimpressive, though the finding that low galectin-3 levels predicted low cardiovascular risk is novel, highly interesting, and deserving of further study.

Meanwhile, guidelines are already taking notice of an emerging consensus on the value of imaging studies as a negative risk factor.

The 2018 prevention guidelines from the American College of Cardiology/American Heart Association recommend coronary artery calcium (CAC) testing to guide individualized patient decision-making in certain adults between the ages of 40 and 75 years who are at borderline to intermediate risk, and that using CAC results to reclassify risk is reasonable in those aged 76-80 years, they said.

For the first time, the ACC/AHA guidelines devoted a section to negative risk factors, specifically highlighting the value of CAC = 0 and stating that intensive statin therapy is of less value in such patients and can potentially be avoided.

Likewise, 2017 guidelines from the Society of Cardiovascular Computed Tomography say that aspirin for primary prevention can almost always be forgone in patients with a CAC of 0.

“The bar for preventive therapy has justifiably fallen, reaching a point where many patients will qualify based on their age alone,” the authors said.

In light of that development, negative risk factors might meaningfully downgrade risk and help identify individuals who can safely focus on lifestyle therapies and defer preventive medication.

Michael J. Blaha, MD, MPH, and Khurram Nasir, MD, MPH are with the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore; Dr. Nasir also is affiliated with the Center for Outcomes Research and Evaluation, Yale University, New Haven, Conn. Ron Blankstein, MD, is with the cardiovascular division, department of medicine, Brigham and Women’s Hospital, Boston. These comments are adapted from their editorial (J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.05.032 ). Dr. Blankstein reported research funding/grant support from Amgen and Astellas; Dr. Blaha and Dr. Nasir said they had no disclosures to report.



Older individuals with certain negative risk markers have a very low risk of atherosclerotic cardiovascular disease, raising the possibility that some could forgo preventive treatment even if it’s indicated by current standards of risk assessment.

Low levels of coronary artery calcification (CAC), low galectin-3 levels, and absence of carotid plaque were all linked to a lower likelihood of disease than might be expected based on traditional risk assessment, according to the authors of analysis of a large, contemporary cohort of elderly individuals published in the Journal of the American College of Cardiology.

“Our results hold the potential to markedly improve statin allocation in elderly individuals by de-escalating or even withholding preventive therapy in elderly individuals at truly low atherosclerotic cardiovascular disease risk despite advancing age,“ wrote Martin Bødtker Mortensen, MD, PhD, of Aarhus (Denmark) University Hospital.

Most elderly individuals now qualify for lifelong preventive statin treatment, based on the broader indication for treatment in recent guidelines, and the substantial impact that age has when risk is being calculated, Dr. Mortensen and coauthors said in their report.

“Because frailty, comorbidity, and polypharmacy are increasing concerns in elderly individuals and have been proposed to increase the risk for adverse effects, the appropriateness of treating almost all elderly individuals is questionable,” they said in the report.

In their study, Dr. Mortensen and colleagues evaluated a set of 13 biomarkers or imaging tests that they though had potential to “downgrade” risk of coronary heart disease (CHD) and cardiovascular disease (CVD). They based their analysis on 5,805 patients in the BioImage Study, a prospective cohort study of elderly men and women with no atherosclerotic cardiovascular disease at the time of enrollment in 2008 and 2009. The mean age at the time of enrollment was 69 years, and the mean follow-up in this analysis was 2.7 years.

The overall rate of CHD was 6.1 per 1,000 person-years, though looking at negative risk markers, the event rate was just 0.9 for individuals with CAC of 0 and also 0.9 for those with a CAC of 10 or less, followed by 1.7 for absence of carotid plaque, and 2.6 for galectin-3 in the bottom 25th percentile, according to Dr. Mortensen and coinvestigators. Similarly, the rate of CVD was 9.2 per 1,000 person-years overall, and just 3.2 for a CAC of 0, 2.8 for a CAC of 10 or lower, 4.4 for no carotid plaque, and 4.0 for low galectin-3.

Results were less impressive for other negative risk markers, including normal ankle-brachial index (ABI) test, lack of family history, and low levels of circulating biomarkers such as high-sensitivity C-reactive protein and lipoprotein (a).

Investigators also calculated diagnostic likelihood ratios (DLR), a measure they said assesses the value of performing a diagnostic test, with values lower than 1 indicating a specific marker has value for downgrading risk.

Zero or low CAC exerted the greatest downward change in pre- to post-test risk, according to the investigators, with a multivariable-adjusted DLR of 0.20 for CHD, translating into an 80% relative risk reduction. Similarly, the adjusted DLRs for zero or low CAC for CVD were 0.48 and 0.41, respectively, translating into a 59% risk reduction.

Low galectin-3 also resulted in significant downward change in that pre- to post-test risk, investigators added.

The BioImage Study was funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Dr. Mortensen had no disclosures related to the present analysis. Coauthors provided disclosures related to G3 Pharmaceuticals, Abbott Laboratories, AstraZeneca, Bayer, Bristol-Myers Squibb, CSL Behring, Eli Lilly/DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and PLC/Renal Guard, among others.

SOURCE: Mortensen MB et al. J Am Coll Cardiol. 2019 Jul 1. doi: 10.1016/j.jacc.2019.04.049.

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