Pooled Cohort Equations Work in Real-world Patients, Even Outliers

A decade after they were first introduced, the American College of Cardiology (ACC)/American Heart Association (AHA) pooled cohort equations (PCE) for atherosclerotic cardiovascular disease (ASCVD) remain a beneficial tool for primary prevention, even for patients who might fall outside of its traditional constraints, according to real-world clinical data.

The PCE were introduced in 2013 to aid in the clinical decision-making process for assessing a patient’s ASCVD risk, and they’re recommended by current guidelines. However, some studies have suggested the tool might overestimate risk when applied to certain populations who were not included in the original derivation cohorts, including those with underrepresented social and ethnic backgrounds and those on statins.

These findings should be reassuring to clinicians who use the PCE regularly during preventive visits, lead author Jose R. Medina-Inojosa, MD, MSc (Mayo Clinic, Rochester, MN), told TCTMD. “When you have a patient that doesn't fall within the normal numbers of what the original calculator was [when it was] made several years ago, you can still have good enough information to decide whether to start some of this therapy,” he said.

In an accompanying editorial, Donald M. Lloyd-Jones, MD, ScM (Northwestern Feinberg School of Medicine, Chicago, IL), writes that the data are confirmation that the PCE “have stood the tests of time and science” and that clinicians should have “even greater confidence” in their utility.

“As such, they are well tailored to begin the discussion regarding risk and need for medical therapy for primary prevention of ASCVD,” he says. “After this initial step, the personalization of risk to the individual patient through consideration of individual risk-enhancing factors and the use of coronary artery calcium testing in selected patients to reclassify risk, in the context of a clinician-patient discussion, will lead to smarter recommendations regarding which patients should take low-density lipoprotein cholesterol–lowering therapy and which patients may reasonably defer medication initiation.”

Similarly, Ashish Sarraju, MD (Cleveland Clinic, OH), commenting on the findings for TCTMD, said the data support his current use of the PCE as a first step with all of his prevention patients. They also confirm that the other common practice of entering the highest allowable numbers into the PCE, when applicable, is effective. “It seems to validate what I suspect a lot of us do in practice, when someone’s lab values or blood pressure are outside the range of what the pooled cohort equation allows us to use,” he said.

The findings were published in the October 10, 2023, issue of the Journal of the American College of Cardiology.

PCE Hold Up

For the study, Medina-Inojosa and colleagues included 30,042 adults from Olmstead County, MN, without known ASCVD (mean age 48.5 years; 46% male). Overall, mean ASCVD risk at baseline was 5.6%. Median follow-up was 16.5 years, but this was truncated at 10 years for this analysis.

ASCVD events were reported in 5.2% of the population over follow-up. Overall, the PCE performed well (C-statistic 0.78), as well as in sex and race subgroups. Performance was highest among nonwhite females (C-statistic 0.81) and lowest in white males (C-statistic 0.77).

Sensitivity analyses including 32,051 participants with values out of range from the traditional PCE values—including age < 40 or >79 years; systolic blood pressure < 90 or > 200 mm Hg; or total cholesterol < 130 or > 230 mg/dL—and 29,873 who had been initiated on statins showed no differences in model performance.

Next, Medina-Inojosa said he would like to see more focus on uncovering “what the current risk enhancers are,” especially for those with higher pretest probabilities for cardiovascular events, like patients with chronic kidney disease, hypertensive disorders of pregnancy, and inflammatory conditions. “More research needs to be now put into understanding what do we need to do for these populations [in whom] we already understand that the risk prediction is different,” he said.

Additionally, “understanding the utility of and the yield of information that we get from tools such as coronary artery calcium” also deserves more attention, Medina-Inojosa said.

More Precise Tools Coming

Sarraju said “there's utility in thinking about these risk factors, even before someone may hit that 5% threshold.” For example, thinking about lifelong risk for a young adult with prediabetes, obesity, or uncontrolled hypertension, “even if they do not meet the pooled cohort equation borderline risk threshold, . . . is [key to] earlier primary prevention and primordial prevention,” he said.

It’s a matter of when, not if, newer, more precise risk tools will emerge that include nontraditional risk factors, according to Lloyd-Jones. “Future guidelines may also move beyond consideration of quantitative risk alone and incorporate quantitation of expected benefit from drug therapy,” he says. “These advances will be welcome.”

For now, he urges clinicians “to focus on implementing the existing guidelines, given that use of preventive therapies for primary prevention is well below optimal in our patients who face the very real risks of ASCVD events given the increasing burdens of dyslipidemia, hypertension, diabetes, and other comorbidities in the population.”