“Routine” medication nonadherence in CV trials impacts outcomes regardless of intervention

August 15, 2022

5 minute read

Disclosures:
Terumo supported the MASTER DAPT trial. Baber reports receiving fees from Amgen and AstraZeneca. Spertus claims copyright to the Kansas City Cardiomyopathy Questionnaire and the Seattle Angina Questionnaire; receive consulting fees from Abbott, Bayer, Bristol Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo; receive research grants from Abbott Vascular, Janssen, and MyoKardia; receive honoraria from the Scientific Advisory Board of United Healthcare; and board member of Blue Cross Blue Shield of Kansas City. Please see the studies and editorial for relevant financial information from all other authors.


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Two analyzes of large randomized controlled trials suggest that participants not taking prescribed medications may influence treatment effects and the results of impact studies, the researchers reported.

In analyzes assessing non-adherence to medications for the ISCHEMIA and MASTER DAPT trials, researchers found that the detrimental effect of non-adherence – poorer health status – was consistent across patients randomly assigned to n any treatment, data showing that more invasive strategies do not benefit non-adherent participants.

Graphical representation of the source citation presented in the article

Data are from Valgimigli M, et al. J Am Coll Cardiol. 2022; doi:10.1016/j.jacc.2022.04.065.

“A unifying theme in both studies is that medication nonadherence is common, even in the controlled settings of high-quality, rigorously conducted clinical trials,” Usman Baber, MD, MS, associate professor of medicine and director of interventional cardiology and the cardiac catheterization laboratory at the University of Oklahoma Health Sciences Center, and colleagues wrote in a related editorial discussing the two studies. “This presents a sobering challenge to the clinician practitioner who must deal with a healthcare environment in which value-based reimbursement models often view medication adherence as a measure of quality, but the time allocated encounters with patients continues to decline.”

ISCHEMIA Membership

As Healio previously reported, data from the ISCHEMIA trial showed that an invasive strategy (optimal medical therapy plus diagnostic catheterization, followed by PCI or CABG depending on catheterization results) and a strategy Conservative optimal medical therapy yielded similar long-term CV outcomes in stable patients with moderate or severe ischemia. In the new analysis, the researchers compared the 12-month health status outcomes of ISCHEMIA adherent and non-adherent participants, with an a priori hypothesis that non-adherent patients would have better health status if they were randomly assigned to invasive treatment.

John A. Spertus

“While we initially hypothesized that an invasive management strategy would be more beneficial in patients who were not very compliant with their medications, this is not what we found,” John A. Spertus, MD, MPH, professor and Daniel J. Lauer Chair in Metabolism and Vascular Disease Research at the University of Missouri-Kansas City School of Medicine, Healio told Healio. “In fact, we found that the health status of patients who were compliant were better with conservative and invasive treatment strategies, and this underscores, in my opinion, how important it is to work with our patients to s ensure 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 this is a barrier to their adherence.

Spertus and colleagues assessed self-reported medication-taking behavior at randomization for 4,480 ISCHEMIA participants, using a modified Morisky-Green-Levine four-item medication adherence scale to classify participants as adherent or not members. The researchers then assessed the participants’ health status over 12 months via the Seattle Angina Questionnaire-7 (SAQ-7) summary score, which ranges from 0 to 100.

Within the cohort, 27.8% were non-adherents at the start.

The researchers found that, compared to adherent participants, non-adherent participants had worse baseline SAQ-7 summary scores in the conservative (mean, 72.9 versus 75.6) and invasive (mean, 71 versus 74) arms. ,2). In the adjusted analyses, adherence was associated with higher SAQ-7 summary scores over 12 months in both treatment groups. The mean difference in SAQ-7 summary scores for adherence compared to non-adherent participants was 1.6 for the conservative treatment group (95% credibility interval [CrI]0.3-2.9) and 1.9 for the invasive treatment group (95% CrI, 0.8-3.1), with no interaction with the treatment.

Spertus said more strategies are needed to better support medication adherence for patients with chronic coronary heart disease.

“Working with our patients to better understand the purpose and potential benefits of adhering to their medications – having fewer symptoms, being able to do more, and having a better quality of life – is important whether they are treated or not with stents, CABG or drugs alone,” Spertus told Healio.

Membership of the MASTER DAPT

As Healio previously reported, MASTER DAPT evaluated 4,579 patients (mean age, 76 years; 69% male) at high risk of bleeding who underwent PCI with a biodegradable polymer sirolimus-eluting stent (Ultimaster , Terumo) at 1 month or at least 3 months of dual antiplatelet therapy. Randomization occurred 1 month after PCI, after which the abbreviated treatment group discontinued DAPT and the standard treatment group continued DAPT for at least an additional 2 months. DAPT consisted of aspirin and a P2Y12 inhibitor; the sole antiplatelet therapy consisted of either of these.

There was no difference between the groups in terms of net adverse clinical events or MACCE; however, clinically relevant major or non-major bleeding occurred less often in the abbreviated treatment group compared to the standard treatment group. The groups did not differ in rates of all-cause death, myocardial infarction, or stent thrombosis, but strokes or transient ischemic attacks occurred twice as often in the standard treatment group as in the abbreviated treatment group.

In a new analysis, researchers investigated the impact of non-adherence to study protocol treatment regimens in the MASTER DAPT trial. Temporary or permanent nonadherence was defined as 3 or more days of missed medication in all four antiplatelet therapies; Adherence to study medications was assessed by inspecting clinical records during follow-up and by patient investigators.

Across all groups, 20.2% of patients in the abbreviated treatment group and 9.4% in the standard treatment groups did not adhere to the treatment protocol. Using analyzes of inverse censoring probability weights, net adverse clinical events (HR=1.01; 95% CI, 0.88-1.27) or MACE (HR=1.07; CI at 95%, 0.83-1.4) did not differ, and major or clinical events relevant non-major bleeding were lower with abbreviated treatment compared to standard treatment (RR = 0.51; 95 CI %, 0.6-0.73) consistently across oral anticoagulation subgroups; in patients on oral anticoagulation, discontinuation of single antiplatelet therapy 6 months after PCI was associated with similar MACE and lower bleeding risk (HR=0.47; 95% CI, 0.22-0 .99) compared to continuation of single antiplatelet therapy.

“By primarily correcting for patterns of nonadherence in patients on oral anticoagulation 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 of bleeding without an increase in ischemic events in this patient subset,” the researchers wrote.

“We have to do a better job”

In the editorial, Baber and colleagues noted that strategies to improve 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 drug costs (i.e. co-pay vouchers) or polypharmacy (i.e. polypills), produced modest effects on adherence with no appreciable impact on surrogate or hard clinical outcomes,” Barber and colleagues wrote. “Conversely, improved patient-clinician communication vis-à-vis shared decision-making leads to greater gains in medication adherence in the general population and minority cohorts. At the heart of this operational paradigm is finds the active participation of patients and clinicians.

“While effective tools that improve medication adherence are already available to us, we need to do a better job of implementing these strategies if patients are to fully realize the benefits of medications that reduce cardiac risk and improve quality of life,” Baber and his colleagues wrote.

References:

Baber U, et al. J Am CoII heartbeat. 2022; doi:10.1016/j.jacc.2022.06.010.

Garcia RA, et al. J Am CoII heartbeat. 2022; doi:10.1016/j.jacc.2022.05.045.

For more information:

John A. Spertus, MD, MPH, can be attached to [email protected].

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