Even With Revascularization in ISCHEMIA, Skipping Meds Hurt Health Status

Medication nonadherence was common and associated with worse health status among the patients with stable coronary disease in the ISCHEMIA trial, regardless of whether they underwent conservative or invasive management.

Roughly one-quarter (27.8%) were nonadherent, and this group had lower average summary scores on the seven-item Seattle Angina Questionnaire (SAQ-7) both at baseline and after a year of follow-up compared with those who were better at taking their medications, according to researchers led by R. Angel Garcia, DO (Saint Luke’s Mid America Heart Institute, Kansas City, MO).

They had hypothesized that the adverse impact of poor medication adherence—which has been shown to be a pervasive problem associated with worse clinical outcomes across cardiovascular medicine—would be lessened in patients randomized to invasive management since they were receiving additional treatment on top of guideline-directed medical therapy, but that wasn’t the case.

That finding is surprising, said study author John Spertus, MD (Saint Luke’s Mid America Heart Institute). “In the invasive arm, it underscores that not only do we need to do as complete a revascularization as possible, but we also need to . . . focus on making sure that patients are adherent with their medical therapy, which is also important for optimizing their symptoms and minimizing their long-term risk,” he told TCTMD.

Moreover, nonadherence is not a good reason to preferentially choose invasive over conservative management for an individual patient, Spertus said. “Working with that patient to understand why they have difficulty adhering to their medicines is really quite important, and that effort needs to be done both in patients with medicines alone and those referred for an invasive strategy and revascularization.”

Adherence in ISCHEMIA

The study, which was published in the August 23, 2022, issue of the Journal of the American College of Cardiology, used data from the ISCHEMIA trial, which randomized patients with stable chronic coronary disease and moderate or severe ischemia to either guideline-directed medical therapy alone or medical therapy plus angiography and revascularization when indicated. There were no differences between strategies for primary or secondary clinical events, although invasive management was associated with better health status among patients who had angina at baseline.

This analysis focused on the 4,480 patients who had quality-of-life and medication adherence assessments available. Health status was evaluated using the SAQ-7, which provides summary scores ranging from 0 to 100 (higher scores are better). Self-reported medication-taking behavior was assessed at randomization using a modified four-item Morisky-Green-Levine Adherence Scale.

At baseline, patients deemed to be nonadherent had worse SAQ-7 summary scores, both in the conservative arm (mean 72.9 vs 75.6) and in the invasive arm (mean 71.0 vs 74.2).

Health status improved during the first year of follow-up, but nonadherent patients continued to fare worse compared with those who adhered to their treatment regimens—by an average of 1.6 points in the conservative arm and 1.9 points in the invasive arm after adjustment. The results were consistent when looking at the specific SAQ-7 domains of angina frequency, physical limitation, and quality of life.

Asked why invasive management didn’t mitigate the effects of poor medication adherence on health status, Spertus noted that research has shown that many patients will continue to have angina even after coronary revascularization. “For those patients, concomitant antianginal therapy can be very beneficial,” he added.

Another potential explanation “is that patients who are adherent are fundamentally different than patients who are nonadherent,” he said, noting that those who are better at taking their medications may be more educated or more motivated to take care of themselves. Thus, “it’s possible that reported adherence is a marker for other things that patients do to optimize their health status, and it’s some of those other things like regularly exercising, following a better diet, things of that sort, that are really responsible for the observed differences in health status and it’s not just adherence to medicine.”

No ‘Magic Bullet’

According to P. Michael Ho, MD, PhD (University of Colorado Anschutz Medical Campus and VA Eastern Colorado Health Care System, Aurora, CO), who was not involved in the study, it’s difficult to interpret that finding because adherence was assessed by self-report and only at baseline.

“We don’t know if their adherence behavior changed over the course of the study,” he commented via email. “Since medication-adherence behavior can change over time and particularly in a closely monitored environment of a clinical trial, it is not clear if patients changed their behaviors during participation in the study and whether the invasive management could have had a differential impact on patient symptoms.”

Nonetheless, the analysis “highlights that we still have much work to do to try to improve both medication nonadherence and patient symptom burden,” Ho said.

And that won’t be an easy task, he indicated. “There really is not a one-size-fits-all [solution] for addressing medication nonadherence since there may be many different reasons for poor medication adherence among patients,” he explained.

“One thing that we can do is to incorporate the assessment of medication adherence in every clinical visit, such as incorporating it as a vital sign,” Ho recommended. “Nonadherence is commonly under-recognized, so I think the first step is to recognize it. Depending on the patient-specific reasons for poor medication adherence, there are some evidence-based solutions to address it, although most interventions to date have had modest effects. I think we still need more studies to assess the impact of interventions on medication adherence.”

Spertus agreed that there is no “magic bullet” when it comes to addressing problems with medication adherence, which can stem from a variety of causes. “There’s a real need to think through with each individual patient what is their key gap in being able to adhere to those medicines and then working with them to figure out how to [address] those,” he said.

This study and another looking at medication nonadherence in the MASTER DAPT trial “reinforce the high prevalence of medication nonadherence and its potential impact on both estimates of treatment effect and health outcomes,” Usman Baber, MD (University of Oklahoma Health Sciences Center, Oklahoma City), and colleagues write in an accompanying editorial. “While effective tools that enhance medication adherence are already available to us, we must do a better job of implementing these strategies if patients are to fully realize the benefits of medications that lower cardiac risk and improve quality of life.”