Coronary Calcium-Guided Statin Strategy Cost-effective in African-Americans

Using the coronary artery calcium (CAC) score to guide the start of statin therapy is a more cost-effective strategy than simply adopting a “statins for all” approach in African-Americans at intermediate risk for atherosclerotic cardiovascular disease (ASCVD), according to a new analysis from the Jackson Heart Study.

The findings, however, were highly sensitive to patient preference, say investigators. For those who didn’t mind taking a daily pill, statins for all intermediate-risk patients was a cost-effective strategy, but in those with a strong preference to avoid taking a lifelong statin, the CAC-guided strategy cost less and resulted in better outcomes.

“There’s a real preference among some patients where the simple act of taking a pill every day for their heart health makes them feel worse about their health,” senior investigator Ankur Pandya, PhD (Harvard T.H. Chan School of Public Health, Boston, MA), told TCTMD. “For, say, 75% of the population, they don’t care, and that’s controlling for side effects, controlling for costs. The act of taking a pill every day, 75% would think of it as taking a vitamin. Another 10% to 20% have real strong feelings about this to the extent where they’d be willing to trade years off their life to avoid taking that pill.”

Previous cholesterol guidelines had been criticized for overtreating primary-prevention patients with statins, so the 2018 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines introduced noninvasive CAC scoring to help make decisions about intermediate-risk patients who fall into the gray zone for treatment. Several observational studies, including MESA, BIOIMAGE, and others, have shown that a CAC score of zero can identify patients with such a low 10-year risk of ASCVD that they are able to avoid statin therapy.  

Speaking with TCTMD, Ron Blankstein, MD (Brigham and Women’s Hospital, Boston, MA), the president of the Society of Cardiovascular Computed Tomography, said the 2018 ACC/AHA cholesterol guidelines highlight shared decision-making, which means physicians should have a conversation with patients about their preferences, noting that some have a strong desire to avoid statins while others are unbothered.

“Patients are sometimes willing to give up months of their lives just to avoid being on statin therapy,” said Blankstein. “Even though statins are, in general, very safe and well tolerated by most people, the idea of being on a statin, especially for what patient’s see as their lifetime, that idea is really not appealing to a lot of folks.”

In clinical practice, Blankstein frequently encounters patients resistant to starting statin therapy, even in patients with known ASCVD. For some, it can be a considerable source of distress, and they’d rather do anything possible to avoid treatment. That said, that “disutility” can be modified. “From my own experience, once we do a calcium score and we show patients images of the plaque in their arteries, their willingness to treat it and perhaps be on a statin often changes,” he said. CAC scoring, he noted, can improve acceptance of statin therapy, as well as promote adherence.

Factoring in ‘Disutility’

The new cost-effectiveness analysis, led by Aferdita Spahillari, MD (Massachusetts General Hospital, Boston, MA), and published May 13, 2020, in JAMA Cardiology, specifically addressed the cost-effectiveness of CAC screening in African-American individuals at intermediate risk for ASCVD. Past studies have raised concerns about the pooled cohort equations used to estimate their 10-year risk of ASCVD, suggesting it may overestimate their risk of disease and potentially lead to overtreatment with statins, according to the investigators.   

Patients are sometimes willing to give up months of their lives just to avoid being on statin therapy. Ron Blankstein.

The researchers compared the cost-effectiveness of the 2013 ACC/AHA guidelines, which recommend statins for those aged 40 to 75 years with LDL cholesterol levels 70 to 189 mg/dL and a 10-year risk of ASCVD 7.5% or greater against the 2018 ACC/AHA cholesterol guidelines. The newest guidelines make a similar recommendation for treatment, but only if the patient has coronary calcification as indicated by a CAC score greater than zero. 

“There’s been a lot of data in our field of cost-effectiveness analyses around the different guidelines,” said Pandya. “The majority of the studies show that when statins are cheap—generic forms of atorvastatin and so on, which cost around $40 per year—it’s actually cost-effective to indicate treatment to almost half, or almost two-thirds, of the adult population over age 40.”

The simulation study included 472 intermediate-risk individuals in the Jackson Heart Study, of whom 304 underwent CAC testing. Of these, 42.4% of patients had a CAC score of zero. The cost data, clinical event rates, probabilities, and quality of life (utility) information were taken from previously published data and individual patient data in the study. In their base case, they researchers included a small disutility, or the annual quality-of-life reduction for taking statins, of 0.00384 life-years. This was the equivalent of a patient willing to give up 2 weeks of ideal health to avoid 10 years of daily statin use.

In contrast with the 2013 guidelines where everyone received a statin, just 58.6% of intermediate-risk patients qualified for a statin under the 2018 guidelines. In the base case simulation, the 2013 ACC/AHA guidelines resulted in 0.0027 quality-adjusted life-years (QALY) gained over the 2018 guidelines, but the per-person costs were higher ($428.97). This translated into an incremental cost-effectiveness ratio (ICER) of $158,325/QALY gained when compared with the 2018 ACC/AHA guidelines, which is considered low-value care by the ACC/AHA definitions.

In sensitivity analyses, the 2018 ACC/AHA guidelines with the CAC score were cost-effective in 81% of the simulations using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year (QALY) gained when patients were willing to lose 2 weeks of life to avoid 10 years taking a daily statin. They were cost-effective in 76% of the simulations when using a threshold of $100,000 per QALY. If medication disutility was adjusted to 0.991 (as opposed to 0.996 in the base case), a number equivalent to being willing to lose 5 or more weeks of life to avoid 10 years of daily medication, the CAC-guided strategy yielded greater or equal health outcomes at lower costs. If there was no quality-of-life penalty for daily statin therapy, the 2013 guidelines had an ICER of $24,003/QALY.   

“In those patients who have reservations or preferences against taking a statin, that’s where the calcium score really drives the difference,” said Pandya. “For people who don’t mind taking a pill, the old guidelines in this population of African-Americans seem fine. You just give them the pill, it doesn’t matter. They’re effective, they’re cheap, and they’re pretty safe.”

Specific to the simulation model, Blankstein said the assumptions made were quite conservative, which is appropriate in modelling studies, but that they might even be a little too conservative. For example, the base-case cost of the CT scan, assumed to be $183, is cheaper in some centers. Additionally, the annual costs of diabetes associated with statins, which was assumed to be $4,729, might be an overestimate as statins are unlikely to cause diabetes in patients who are not already predisposed to the disease. The net effect of the conservative model is that the magnitude of benefit seen in the cost-effective analysis might be even larger in real life.

Fundamental Shift  

In general, Blankstein said there has been a fundamental shift in the thinking around CT-derived CAC scoring. Today, it is not a screening test so much as an aid to enhance discussions on patient preference in the doctor’s office.

“A screening test takes a low-risk population and you screen them to find out who is at higher risk, who has plaque, and then you treat them,” he said. “With the new guidelines, we’ve turned around how we think about it. It’s no longer a screening test. We’re not doing it in a low-risk patient to find out who to treat. We’re using it in patients who meet the criteria to be on statins, and we’re using that information as a shared decision-making tool.”

In an editorial, Eméfah Loccoh, BS (Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Boston, MA), and Dhruv Kazi, MD (Beth Israel Deaconess Medical Center, Boston, MA), highlight the four in 10 patients spared statin therapy based on the use of CAC scoring under the 2018 ACC/AHA guidelines. Like Blankstein, they state that information gleaned from CT scan be used to inform shared decision-making.

“This study underscores the need for a validated and readily usable instrument to measure patients’ pill-related disutility,” they write. “This would empower clinicians to efficiently provide personalized recommendations for cardiovascular prevention based on insights that extend beyond average estimates for heterogeneous populations.”

Overall, Blankstein said he believes that findings in this population of African-Americans could apply to different patients. In his clinical experience, the resistance to starting statins is similar in African-American and white individuals, as well as other racial/ethnic groups. “In general, I think a lot of the concepts of this paper are generalizable to other populations than were studied,” he said.