Even within the controlled setting of contemporary revascularization trials, adherence to guideline-directed medical therapy (GDMT) is suboptimal, especially in patients undergoing bypass surgery, new research suggests.[1]
A meta-analysis of study-level data from the SYNTAX, FREEDOM, PRECOMBAT, BEST, and EXCEL trials found that overall adherence to antiplatelet therapies, β-blockers, and statins was only 67% at 1 year and fell to 53% at 5 years.
When an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) was added to the core regimen, adherence rates were even lower at 40% and 39%, respectively.
“We were going by what drugs we believed were being prescribed, but in fact it’s possible that the rate of use by the patients was even lower than these numbers,” senior author, Dr David Taggart (Oxford University Hospitals NHS Trust, UK), told theheart.org | Medscape Cardiology.
Notably, adherence to the core therapy regimen was lower at all time points in patients undergoing CABG surgery rather than PCI, which could skew comparison of clinical endpoints between the two strategies.
“It’s very important because in most of these trials CABG had quite a significant survival benefit at 5 years, and what was implied is that had the CABG patients been given equivalent medical therapy to the PCI group, those differences in favor of CABG would have been even greater,” he said.
Indeed, meta-regression of three trials with 5-year follow-up showed a linear correlation with poorer clinical outcomes when CABG patients had lower use of the core therapy regimen. As the adherence gap favoring PCI widened, the superiority of CABG became less evident and disappeared altogether when PCI adherence exceeded that of CABG by about 8%.
No such association was present with clinical outcomes and the more intensive medical regimen.
As to why adherence was lower with the more intensive regimen containing ACE inhibitors/ARBs, Taggart said there was probably less prescribing of it because the benefits of these additional therapies are “certainly present for patients with significantly impaired ventricular function, but much less so for patients with normal ventricular function.”
The study, led by Ana-Catarina Pinho-Gomes, MSc (Oxford University Hospitals NHS Trust), was published online in advance of the February 13 issue of the Journal of the American College of Cardiology.
In a related editorial,[2] Drs Marc Ruel (University of Ottawa Heart Institute, Ontario, Canada) and Alexander Kulik (Lynn Heart and Vascular Institute, Boca Raton, FL) write that hospitalization for coronary revascularization represents a unique opportunity to implement secondary preventive therapies that is “often missed.”
Studies have shown adoption rates barely reaching 60% after revascularization in real-world contemporary practice. “However, within the context of a clinical trial, it would be reasonable to expect high medication compliance rates, given the controlled research environment, select population of patients, and repeat opportunities for study investigators to promote guideline-recommended medications,” they add.
The editorialists suggest low adherence rates in the trials could reflect fewer recurrent symptoms and an underestimation of the value of long-term medical therapy after revascularization.
“It’s possible that CABG patients had less medical therapy partly because they felt so much better; they had a bigger bang for the buck,” Taggart said. But “we can only postulate these things.”
He continued, “I have no question that part of this is that the rationale for staying on these therapies over the long term is not explained to most patients. Because if most patients were educated to understand that these drugs can not only improve the quality of life but life expectancy, there’s not many who would say, ‘No, I’m not interested.'”
Ruel and Kulik call for increased prescribing and improved patient education but also the institution of effective follow-up visits and development of strategies to enhance adherence to GDMT at the patient level. Going forward, clinical investigators also should strive to collect prescription data in CAD trials and implement GDMT for nearly all CAD participants.
While some trials do not even mention medical therapy, GDMT adherence approached 90% in the EXCEL trial, which emphasized its use, observed Taggart, who served on the EXCEL steering committee.
“It just goes to show what can happen if it’s written into the trial as an essential part of the trial,” he said.
Taggart and Pinho-Gomes reported no relevant conflicts of interest. Kulik reported receiving research support from AstraZeneca and Pfizer; Ruel reported having no financial relationships.
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.
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