Compliance With Preventive Drugs After CABG, PCI Found Lacking in Clinical Trials

Even in the context of landmark trials comparing CABG and PCI in patients with complex coronary disease, compliance with guideline-directed medical therapy leaves something to be desired, a meta-analysis shows.

In pooled results from five big-name trials, the percentage of patients prescribed a regimen that included any antiplatelet, a beta-blocker, and a statin was just 67% at 1 year of follow-up, declining to 54% at 5 years, according to Ana-Catarina Pinho-Gomes, MSc (Oxford University Hospitals NHS Trust, England), and colleagues.

Regimens that additionally included an ACE inhibitor or angiotensin receptor blocker (ARB) were used even less frequently—in 40% of patients at 1 year and 39% at 5 years, they report in a study published online ahead of the February 13, 2018, issue of the Journal of the American College of Cardiology.

The situation was even worse following bypass surgery, as compliance with these regimens was higher in patients who had undergone PCI than in those who had undergone CABG at each time point during follow-up. For the more intensive regimen, for example, the difference in adherence favoring PCI was 10% at discharge, 8% at 1 year, 4% at 3 years, and 6% at 5 years.

The discrepancy could influence how the findings of important trials comparing CABG and PCI—which tend to favor CABG—are interpreted, Pinho-Gomes told TCTMD.

“What we can infer is that the difference [in outcomes] between CABG and PCI—if compliance was the same—would . . . favor CABG even more in comparison to PCI,” she said, noting that some nonsignificant results in prior trials could reach statistical significance in such a scenario.

The substandard use of preventive medications in clinical trials could cause ripples in everyday practice, too, because trials should be setting an example by showcasing best practices, Pinho-Gomes said.

“Its’s really important that the trials reflect the best medical treatment that we can provide and it’s astonishing that one of the most recent trials, the NOBLE trial, didn’t even collect data on the medications the patients were on, so they could never take that into account,” she said, indicating that interpretation of the results is muddied by that missing information.

When questioned by TCTMD, however, experts who were not involved in the study said the major message that should be taken away from the analysis is that clinicians need to do a better job at ensuring that patients are on guideline-directed medical therapy after coronary revascularization, regardless of the technique used.

“Whenever a patient comes for coronary revascularization, we need to be as focused on what happens after the patient leaves the hospital as on what happens in the lab or in the OR,” Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), commented to TCTMD. “If we call ourselves interventionalists or surgeons we need to align with all the interventions that work, and that includes many of the medical interventions or even nonmedical interventions such as exercise, smoking cessation, and beyond.”

L. Kristin Newby, MD (Duke University Medical Center, Durham, NC), also underscored that message. “This really just highlights where we’re not doing a good job taking care of people with chronic coronary disease” and shows that use of the guideline-directed therapies evaluated in this study is “pretty pathetic in general,” she said, noting that it’s a problem that hasn’t gotten any better in recent years.

There are some quality-improvement programs aimed at tackling compliance with preventive medications in the outpatient setting, which is the right first step, Newby said. She added, however, that “it’s dramatic and interesting how little progress we’ve made with drugs that we know have fairly substantial mortality and acute coronary events benefits.”

Compliance Influences Clinical Outcomes

Pinho-Gomes and colleagues looked at compliance with guideline-directed medical therapy in five contemporary trials that compared CABG and PCI with DES and reported information on the use of medical therapy during follow-up. The trials included were: SYNTAX, FREEDOM, PRECOMBAT, BEST, and EXCEL.

Compliance with medical therapy was suboptimal overall, although there was much heterogeneity across studies. Use of any antiplatelet, a beta-blocker, and a statin at 1 year, for example, ranged from 38% in PRECOMBAT to 84% in EXCEL.

Kirtane said the fact that the highest rate was seen in EXCEL, the most recent trial, suggests the message about the importance of medical therapy after revascularization is getting out there. “I think that in the present environment we are doing a better job at emphasizing not just guideline-directed medical therapy but other items such as smoking cessation and weight loss and exercise,” he said.

But in all trials, compliance was better after PCI than after CABG, and the investigators found that the magnitude of the disparity was related to 5-year clinical outcomes in the three trials—SYNTAX, FREEDOM, and BEST—with follow-up that long. When the gap between PCI and CABG widened, the advantage of CABG in terms of all-cause mortality, MI, and a composite of all-cause mortality, MI, and stroke shrank. The superiority of CABG was greatest when there was little difference in compliance between the PCI and CABG groups.

Why the Low Rates?

Pinho-Gomes said the main issues hampering adherence to preventive medications are cost and the increased demands in terms of resources, time, and personnel required to keep patients on prescribed medications in the outpatient setting.

Newby also pointed to challenges in the delivery of outpatient care, saying that it’s much harder to advance quality-improvement initiatives, disseminate information, and track and monitor outcomes in that setting compared within the hospital. Outpatient practice is variable, she said, and it’s more difficult to get patients started on necessary medications.

“Physicians are time pressed. They may assume that if it didn’t get started in the hospital somebody didn’t want them on it, or they just don’t have time to think through all the options,” Newby said. “The outpatient setting’s a hard place to practice.”

Pinho-Gomes said that coronary revascularization needs to be seen as a package that includes both the initial procedure and ongoing drug therapy.

Kirtane agreed. “It’s incredibly important that when patients have coronary disease of the severity that merits this type of revascularization, there’s an emphasis not just on the revascularization but also on the medical therapy ensues afterwards,” he said. “As a clinician I always tell my patients that we may be temporarily fixing the issue but if we don’t address the overall picture that’s causing the current issue then that’s not going to be a durable solution.”

In an accompanying editorial, Marc Ruel, MD (University of Ottawa Heart Institute, Canada), and Alexander Kulik, MD (Boca Raton Regional Hospital, FL), say that “as a community of cardiovascular care providers, we must strive to improve [guideline-directed medical therapy (GDMT)] administration rates and provide our patients with these lifesaving medications after coronary revascularization. The initial step, of course, is to write the prescription, but energy also needs to be focused toward improving patient education, instituting effective follow-up visits, and developing strategies to enhance adherence at the patient level.”

And moving forward on the research side, they add, “clinical investigators must direct their energy toward collecting prescription data in CAD trials and strive to implement GDMT for nearly all study subjects. As leaders in the field and frequent co-authors of guideline statements, revascularization trialists have a responsibility to serve as role models in improving GDMT prescription rates.

Note: One of the co-authors, Gregg Stone, MD, is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.