Adherence to medications post-MI is below 50%; beta-blockers offer little incremental benefit

Based on clinical guidelines, three therapies are often prescribed together following acute MI: angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers and statins. But are they equally important?

Maybe not, according to a new study in the Journal of the American College of Cardiology.

In an analysis of more than 90,000 Medicare beneficiaries with those prescriptions, patients adhering to all three therapies showed similar mortality rates as those who were only adherent to ACE inhibitors/ARBs and statins.

“Our observations support the argument that in the current clinical practice, incremental survival benefits associated with use of beta-blockers may be smaller than benefits associated with use of the other two evidence-based preventive therapies,” wrote corresponding author Gang Fang, MS, PhD, from the school of pharmacy at the University of North Carolina, and colleagues.

This is an important topic, the authors wrote, because “patients with multiple comorbidities and polypharmacy have an increased risk of drug–drug interactions and adverse drug events.” In addition, the more medications patients take, the more likely they may be to engage in noncompliance and “tradeoffs”—taking one medication rather than another.

In their study, less than half (49 percent) of patients maintained all three therapies. Adherence was measured over a 180-day period following hospital discharge by analyzing Medicare claims. Patients who filled their prescriptions enough to be covered for at least 80 percent of the days in that period were considered adherent.

The patients were then tracked for up to 18 months following the compliance measurement period to assess the impact of adherence on all-cause death. Average age of the study population was 76.8 and 45 percent were male. There were 9,617 deaths.

Any combination of nonadherence to ACE inhibitors/ARBs or statins was associated with a significant increase in adjusted risk of death—from a 12 percent increase for those who were adherent to ACE inhibitors/ARBs and beta-blockers only to a 65 percent increase for those who were nonadherent to all three therapies.

After nonadherence to all therapies, adherence to beta-blockers only was associated with the next-largest increased risk at 32 percent.

The authors noted a limitation of their study was the reliance on refill data, which didn’t allow for discernment of whether it was the physician or patient who decided to halt the use of certain medications.

In an accompanying editorial, two doctors from Duke University pointed out it is unlikely randomized clinical trials (RCTs) will be undertaken to assess whether beta-blockers offer limited or no incremental benefit when added to ACE inhibitors/ARBs and statins. Among their reasons: Research sponsors, focused on finding new therapies, have little incentive to prove dropping an existing therapy is safe; most trials are unable to determine when dropping a given therapy is safe; and beta-blockers are now generic and relatively low cost, another factor decreasing incentive to limit their use.

The bigger takeaway from the study, according to the Duke doctors, is that fewer than half of the patients adhered to all three of their prescribed medications.

“Investment in the evaluation of adherence interventions to date has been miniscule in comparison to the huge sums spent on RCTs of new therapies,” wrote Eric D. Peterson, MD, and Ann Marie Navar, MD. “This underinvestment in implementation seems short-sighted, if not paradoxical—sponsors spend billions of dollars on the development of a new drug only to accept that a majority of patients will likely discontinue their therapy within 6 months. …

“The field of medicine should learn from their colleagues in marketing, behavioral economics, and social science to identify which levers are most effective for improving patient medication adherence, and then test the impact of moving those levers in large outcomes trials.”