‘Common’ medication nonadherence in CV trials impacts outcomes, regardless of intervention
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Two analyses of large randomized controlled trials suggest that participants not taking medications as prescribed may influence treatment effects and impact study findings, researchers reported.
In analyses assessing medication nonadherence for the ISCHEMIA and MASTER DAPT trials, researchers found that the detrimental effect of nonadherence — worse health status — was consistent among patients randomly assigned to any treatment, with data showing more invasive strategies do not benefit nonadherent participants.
“A unifying theme across both studies is that medication nonadherence is common, even in the controlled setting of high-quality and rigorously conducted clinical trials,” Usman Baber, MD, MS, associate professor of medicine and director of interventional cardiology and of the cardiac catheterization laboratory at the University of Oklahoma Health Sciences Center, and colleagues wrote in a related editorial addressing the two studies. “This presents a sobering challenge to the practicing clinician who must contend with a health care environment wherein value-based reimbursement models often consider medication adherence a quality metric, yet time allotment for patient encounters continues to decline.”
ISCHEMIA adherence
As Healio previously reported, data from the ISCHEMIA trial showed an invasive strategy (optimal medical therapy plus diagnostic catheterization, followed by PCI or CABG based on catheterization results) and a conservative strategy of optimal medical therapy yielded similar long-term CV outcomes in stable patients with moderate or severe ischemia. In the new analysis, researchers compared 12-month health status outcomes of adherent and nonadherent participants in ISCHEMIA, with an a priori hypothesis that nonadherent patients would have better health status if randomly assigned to invasive management.
“While we originally hypothesized that an invasive management strategy would be more beneficial in patients who were not very compliant with their medications, that was not what we found,” John A. Spertus, MD, MPH, professor and Daniel J. Lauer Endowed Chair in Metabolism and Vascular Disease Research at the University of Missouri-Kansas City School of Medicine, told Healio. “In fact, we found that the health status of patients who were compliant was better with both conservative and invasive treatment strategies, and this underscores, in my mind, how important it is to work with our patients to be sure that they understand the purpose and importance of taking their medications and that we work with them to find strategies to support their access to these medications, if that is a barrier to their compliance.”
Spertus and colleagues assessed self-reported medication-taking behavior at randomization for 4,480 ISCHEMIA participants, using a modified four-item Morisky-Green-Levine Medication Adherence Scale to classify participants as adherent or nonadherent. Researchers then assessed participants’ 12-month health status via the Seattle Angina Questionnaire-7 (SAQ-7) summary score, which ranges from 0 to 100.
Within the cohort, 27.8% were nonadherent at baseline.
Researchers found that, compared with adherent participants, nonadherent participants had worse baseline SAQ-7 summary scores in the conservative (mean, 72.9 vs. 75.6) and invasive (mean, 71 vs. 74.2) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 summary scores in both treatment groups. The mean difference in SAQ-7 summary scores for adherence vs. nonadherent participants was 1.6 for the conservative treatment group (95% credible interval [CrI], 0.3-2.9) and 1.9 for the invasive management group (95% CrI, 0.8-3.1), with no interaction by treatment.
Spertus said more strategies are needed to better support medication adherence for patients with chronic coronary disease.
“Working with our patients for them to better understand the purpose and potential benefits to adhering to their medications — having fewer symptoms, being able to do more and having a better quality of life — is important, regardless of whether they are treated with stents, CABG or medications alone,” Spertus told Healio.
MASTER DAPT adherence
As Healio previously reported, MASTER DAPT assessed 4,579 patients (mean age, 76 years; 69% men) at high bleeding risk who underwent PCI with a biodegradable-polymer sirolimus-eluting stent (Ultimaster, Terumo) to 1 month or at least 3 months of dual antiplatelet therapy. Randomization occurred 1 month after PCI, after which the abbreviated therapy group stopped DAPT and the standard therapy group continued DAPT for at least 2 more months. DAPT consisted of aspirin and a P2Y12 inhibitor; single antiplatelet therapy consisted of either of those.
There was no difference between the groups in net adverse clinical events or MACCE; however, major or clinically relevant nonmajor bleeding occurred less often in the abbreviated therapy group vs. the standard therapy group. The groups did not differ in rates of all-cause death, MI or stent thrombosis, but stroke or transient ischemic attack occurred twice as often in the standard therapy group vs. the abbreviated therapy group.
In a new analysis, researchers investigated the impact of nonadherence to study protocol regimens in the MASTER DAPT trial. Temporary or permanent nonadherence was defined as 3 or more days of missed drug intake across the four antiplatelet therapies; adherence to study medications was assessed by inspecting clinical records during follow-up and by patient interviewers.
Across groups, 20.2% patients in the abbreviated-treatment and 9.4% in the standard-treatment groups were nonadherent to medication protocol. Using inverse probability-of-censoring weights analyses, net adverse clinical events (HR = 1.01; 95% CI, 0.88-1.27) or MACE (HR = 1.07; 95% CI, 0.83-1.4) did not differ, and major or clinically relevant nonmajor bleeding was lower with abbreviated compared with standard treatment (HR = 0.51; 95% CI, 0.6-0.73) consistently across oral anticoagulation subgroups; among oral anticoagulation patients, single antiplatelet therapy discontinuation 6 months after PCI was associated with similar MACE and lower bleeding risk (HR = 0.47; 95% CI, 0.22-0.99) compared with continuation of single antiplatelet therapy.
“By mainly correcting nonadherence patterns in oral anticoagulation patients in the abbreviated treatment group, this analysis suggests, for the first time, that discontinuation of single antiplatelet therapy at 6 months after PCI is associated with less bleeding without an increase of ischemic events in this patient subset,” the researchers wrote.
‘We must do a better job’
In the editorial, Baber and colleagues noted that strategies aimed at improving adherence must consider multiple factors, including comorbidities, the health care system and socioeconomic background.
“Unimodal interventions that target a specific determinant of adherence, such as medication costs (ie, copay vouchers) or polypharmacy (ie, polypills), have yielded modest effects on adherence with no appreciable impact on surrogate or hard clinical outcomes,” Barber and colleagues wrote. “Conversely, enhancing patient-clinician communication vis-à-vis shared decision-making yields larger gains in medication adherence in both general population and minority cohorts. Central to this operational paradigm is the active participation of both patients and clinicians.
“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,” Baber and colleagues wrote.
References:
Baber U, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2022.06.010.
Garcia RA, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2022.05.045.
For more information:
John A. Spertus, MD, MPH, can be reached at spertusj@umkc.edu.
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