Adherence to medical therapy for secondary prevention was generally low in trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) and may have even inadvertently given stenting an advantage in these clinical studies, according to a meta-analysis of large clinical trials.
Guideline-directed medical therapy (GDMT) in terms of the combination treatment with antiplatelets, beta-blockers, and statins was prescribed to 67% at year 1 after coronary revascularization and 53% at year 5. Compliance fell even lower — 40% at year 1 and 38% at year 5 — when the recommended treatment list included the use of ACE inhibitors or angiotensin receptor blockers (ARBs).
“Despite the compelling benefits demonstrated by GDMT as secondary prevention after coronary revascularization, compliance remains low even in the tightly controlled environment of clinical trials,” Ana-Catarina Pinho-Gomes, MSc, of Oxford’s John Radcliffe Hospital in England, and colleagues wrote in the Feb. 13 issue of the Journal of the American College of Cardiology.
Notably, adherence to the guidelines was consistently lower after CABG than with PCI. “The difference was particularly marked for P2Y12-receptor inhibitors, as dual antiplatelet therapy is formally recommended in the guidelines after PCI,” the researchers noted.
“The better outcomes achieved with CABG versus PCI became less obvious as the compliance with GDMT increased in PCI versus CABG. Therefore, if compliance rates were identical in both groups, the superiority of CABG for major clinical endpoints might have been even more marked, as part of the benefit of PCI might be explained by better compliance with GDMT,” the investigators suggested.
Their meta-analysis included five trials: SYNTAX, FREEDOM, PRECOMBAT, BEST, and EXCEL.
Pinho-Gomes’ group said that the underuse of GDMT, particularly after CABG, may be related to the misconception that the value of maintaining GDMT is reduced once diseased coronary arteries have been mechanically revascularized with either PCI or CABG.
“In keeping with this, medical therapy is often neglected in coronary revascularization trials and hence poorly reported or not even collected at all, as happened in the recent NOBLE trial,” they pointed out.
“From a research perspective, going forward, clinical investigators must direct their energy toward collecting prescription data in [coronary artery disease] 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,” said Marc Ruel, MD, MPH, of the University of Ottawa Heart Institute in Ontario, and Alexander Kulik, MD, MPH, of Boca Raton Regional Hospital in Florida.
In an accompanying editorial, Ruel and Kulik suggested that this must be done, even if it means providing trial participants with full coverage for secondary prevention therapy. “Ultimately, improving compliance with GDMT both in and out of the clinical trial context will help our patients achieve the highest level of physical health and quality of life after coronary revascularization,” they said.
Pinho-Gomes and colleagues noted that overall compliance with aspirin and statins was high and reasonably stable over time. There were some differences in antiplatelet prescribing patterns — but considering the controversy regarding dual antiplatelet therapy after coronary revascularization, these differences between trials were not unexpected, either.
It was compliance with beta-blockers and ACE inhibitors or ARBs that was low and more variable, ranging from 43% to 80% and 28% to 79%, respectively, in trials.
“One possible explanation is the fact that although the efficacy of antiplatelet agents and statins in reducing cardiovascular events after coronary revascularization has long been recognized, the advantages of other drug classes have been established more recently and may vary according to comorbidities and risk factors,” the authors suggested.
Limitations of the meta-analysis were that it potentially overestimated medication compliance, because prescriptions were analyzed as a surrogate endpoint; that no patient-level data were available for analysis; and that relatively few trials were included.
Pinho-Gomes and Ruel disclosed no conflicts of interest.
Kulik reported research support from AstraZeneca and Pfizer.
F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner