Noninvasive Testing Can Safely Spare a Large Proportion of Elderly Patients From Statin Therapy
Use of noninvasive imaging to identify subclinical atherosclerosis can help reduce the number of older patients treated with statin therapy without increasing the risk of cardiovascular events among these untreated subjects, a new study shows.
Using coronary artery calcium (CAC) testing and carotid ultrasound to rule out healthy older subjects without disease, researchers “spared” a significant number of individuals—those with CAC and carotid plaque burden scores of zero—from statin therapy without clinical consequences. Overall, the disease-guided approach using noninvasive imaging to assist in statin allocation substantially increased specificity, a reflection of less overtreatment, with only a minor loss in sensitivity.
Speaking with TCTMD, senior investigator Erling Falk, MD, DMSc (Aarhus University, Denmark), said the present study is an attempt to determine if the guidelines for statin therapy could be “personalized” via noninvasive assessment of subclinical atherosclerosis, particularly since the vast majority of elderly patients would qualify for treatment by age alone.
In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for statin therapy expanded the indication for primary-prevention therapy to individuals with LDL cholesterol levels between 70 and 189 mg/dL and a 10-year risk of atherosclerotic cardiovascular disease (ASDVD) of at least 7.5%. However, since atherosclerosis is an age-related disease, Falk said, simply living long enough would make most older patients eligible for statin therapy; this could lead to overtreatment in a patient population already besieged with a number of other medications for clinical conditions.
“We know that elderly people are more vulnerable, have more comorbidity, and have more polypharmacy,” said Falk. “So we think it’s very important that we’re not overtreating them.”
Michael Blaha, MD (Johns Hopkins Hospital, Baltimore, MD), who was not involved in the study, told TCTMD that prior to the 2013 statin recommendations, much of the focus had been directed at finding higher-risk patients who might not have been candidates for statins but who would benefit from treatment based on elevations in a particular risk marker. With the new guidelines, the thinking is now essentially reversed.
“Under the new guidelines, since the threshold for treating is so much lower and the calculator includes heart attack and stroke, among other events, we’re really in a situation where whole blocks of people are either 90% or 100% likely to be candidates for statins, where the biggest driver for this is age,” said Blaha. “Absolutely, if you take an older population, particularly one that has a lot of men in it, and run through the calculation, every Caucasian man above the age of 62 years will be a candidate for statin therapy based on age and race alone.”
The net result is that some are starting to question if the guideline recommendations are “too impersonal,” said Blaha. He, along with Khurram Nasir, MD (Baptist Health Medical Group, Miami, FL), and others, have published studies suggesting that CAC scoring can guide statin therapy and that a “negative” CAC score can shift the 10-year risk of ASCVD. The goal, as with the present study, is to identify patients unlikely to benefit from therapy. In other words, this means assessing “who amongst these large blocks of patients we think might benefit based on the risk calculation are at much lower risk than we previously thought,” said Blaha.
Results of the study, as well as an accompanying editorial, were published online August 22, 2016, ahead of print in the Journal of the American College of Cardiology.
Analyzing Data From the BioImage Study
The BioImage Study included 5,805 participants without ASCVD (mean age 69 years). Of these individuals, the vast majority (86%) qualified for statins based on the 2013 ACC/AHA guidelines. As part of the study, investigators “downclassified” those eligible for statins based on their 10-year risk if CAC screening or carotid ultrasound revealed no subclinical disease. Intermediate-risk subjects in whom statins were optional—those with a 10-year risk between 5% and 7.5%—were “upclassified” to therapy if imaging revealed coronary calcium or carotid plaque burden.
The proportion of patients without subclinical atherosclerosis was “substantial,” said Falk. Overall, 32% of subjects had a CAC score of zero and 23% had no detectable plaque burden on carotid ultrasound.
Over a median of 2.7 years, 91 patients had a first coronary heart disease event (MI, unstable angina, or coronary revascularization without MI or unstable angina) and 138 had a cardiovascular event (MI, unstable angina, coronary revascularization, ischemic stroke, or cardiovascular disease). There was a strong relationship between subclinical atherosclerosis and clinical events, with just three subjects without subclinical disease having a CHD or CVD event.
Given the very minimal number of clinical events among those with no detectable disease on noninvasive imaging, Falk said the study questions whether “it’s reasonable to treat people with that low risk, with that low an event rate, with a statin for the rest of their lives.”
The ACC/AHA risk-based approach to statin allocation had a high sensitivity (96%)—the ability to detect those with disease—but low specificity (15%), which is a reflection of the ability to detect individuals without ASCVD. Using a zero CAC score to downclassify statin-eligible patients, specificity increased from 15% to 25% without any significant loss in sensitivity, according to the investigators. This led to an improvement in the net reclassification index (NRI) for both CHD and CVD. Using the absence of carotid plaque burden on ultrasound to downclassify individuals, specificity also improved, but there was a minor loss in sensitivity. Despite the loss in sensitivity, there remained an improvement in the NRI for CHD and CVD events.
To TCTMD, Falk noted that the improvements in the NRI were driven primarily by downclassifying the larger group of individuals without subclinical atherosclerosis on imaging. “We found a few [subjects], but in fact there was not much room for upclassification of risk because of the risk assessment at baseline, where we already qualified treatment based on the guidelines,” said Falk.
In an editorial, Tasneem Naqvi, MD (Mayo Clinic, Scottsdale, AZ) and Vijay Nambi, MD, PhD (Michael DeBakey Veterans Affairs Hospital, Houston, TX) say the study makes a “compelling argument” to use the absence of clinical disease on imaging to withhold statin therapy. They would like to see a randomized clinical trial show evidence that imaging studies could identify a lower-risk population who might benefit from withholding statins, but in the meantime, physicians can consider such incorporating noninvasive imaging in select patients.
Naqvi and Nambi suggest imaging might be beneficial in individuals who previously experienced statin-related side effects or who are reluctant to take long-term statin therapy. CAC screening or carotid ultrasound might also be used in people with impaired fasting glucose levels, a group at high risk for developing diabetes from statin therapy, to determine if the drugs are truly needed.
Sparing Individuals a Lifetime of Statins, if Possible
In an audio commentary accompanying the study, JACC Editor-in-Chief Valentin Fuster, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who was also one of the study coauthors, said the 2013 clinical guidelines for primary and secondary prevention expanded the number of eligible candidates for statin therapy to approximately 50% of US adult population. Fuster said it is “concerning” that nearly all adults 65 years and older would be eligible for treatment.
This study, however, suggests that using noninvasive imaging can save a significant number of older patients from a lifetime of statin therapy.
“Withholding a statin in individuals without coronary calcification or carotid plaque could spare a significant proportion of particularly elderly people from taking a pill that would benefit only a few,” said Fuster. This disease-guided approach is simple and easy to implement in routine clinical practice.”
In the 2013 clinical guidelines on statin therapy, the ACC/AHA emphasize the importance of shared decision-making between the patient and physician. Falk said the addition of noninvasive imaging, which is used very infrequently in Denmark, as well as in the rest of Europe, can help elderly patients make an informed decision about lifelong LDL-cholesterol lowering therapy with a statin. The decision not to treat in a patient with no evidence of subclinical disease can be as important as treating one with higher risk, particularly since elderly patients are likely taking multiple medications already, he said.
In the editorial, Naqvi and Nambi agree that while the ACC/AHA guidelines for primary-prevention statin therapy make sense on a population level, particularly given that the drugs are safe and inexpensive, the decision is more complicated for individual patients. These individuals have to consider taking a drug that won’t make them feel better, and might come with side effects, to prevent an ASCVD event that might not occur in the next 10 years.
The study is not without limitations, as noted by Fuster as well as by Naqvi and Nambi. Follow-up is short at 2.7 years, although Fuster said there are plans to follow the BioImage Study participants for 10 years. The editorialists also argue that carotid ultrasound, specifically the thresholds used to identify subclinical disease, needs to be validated in other studies. They also point out that there is evidence femoral plaque burden more closely approximates CAC when there are risk factors for ASCVD.
Note: Study co-author Roxana Mehran, MD, is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.
- Mortensen MB, Fuster V, Muntendam P, et al. A simple disease-guided approach to personalize ACC/AHA-recommended statin allocation in people. J Am Coll Cardiol 2016;68:881-891.
- Naqvi TZ, Nambi V. Risk statins or risk “zero” on atherosclerosis imaging for risk stratification. J Am Coll Cardiol 2016;68:892-894.
- ‘Negative’ Atherosclerotic Imaging Results Shift 10-Year CVD Risk Downward: MESA Analysis
- Extent of Coronary Calcium Predicts Long-Term Mortality Risk in Symptom-Free Patients
- Coronary Calcium Goes Beyond CV Risk to Predict a Spate of Other Diseases
- Falk and Blaha report no conflicts of interest.
- Fuster is editor-in-chief of the Journal of the American College of Cardiology.
- Naqvi has received investigator-initiated research grants from Esaote, AtCor Medical, and CardioNexus Corporation related to carotid ultrasound. Nambi is an investigator on a provisional patent filed along with Roche and Baylor College of Medicine on the use of biomarkers in prediction of heart failure, has received an honorarium from Siemens, and has served on the regional advisory board of Sanofi.