Adherence to All Three Drug Classes Important in Post-MI Treatment

October 25, 2013

BOSTON, MA — Patients in the Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) trial who were adherent to treatment with a statin, beta-blocker, or ACE inhibitor/angiotensin-receptor blocker (ARB) were significantly less likely to experience a major vascular event or undergo coronary revascularization[1]. In contrast, individuals who did not take their medication and even those who were only partially adherent to treatment had no significant reduction in clinical outcomes.

"What is important here is that it's true—adherence makes a difference," lead investigator Dr Niteesh Choudhry (Brigham and Women's Hospital, Boston, MA) told heartwire. "When we are confronted by our patients or challenged by them about taking the medications, we often don't have a lot to stand on. This evidence isn't perfect, but it does make a very compelling case that you need to take your meds every day, and each and every one of those medications the guidelines recommend is important. It's that combination of behavior that we should be supporting and will deliver the results for our patients."

The results of the study were published online October 17, 2013 in the American Heart Journal.

"Of Course It Matters!"

MI-FREEE was designed to test whether reducing financial barriers to drug access could improve clinical outcomes in secondary prevention, and the overall results were negative. The study showed that patients who suffered an MI were significantly less likely to have another major cardiac event—defined as an MI, angina, heart failure, or stroke—if the cost of statins, beta-blockers, and ACE inhibitors/ARBs were covered in full by insurance rather than not fully covered (ie, insurance required copayment for the drugs).

However, regarding the primary outcome—a composite of major cardiac events plus revascularization—the difference in events was not statistically significant between the two coverage types.

In the overall trial, adherence to medication increased from 5% to 6%, noted Choudhry. Based on the results, the researchers wanted to determine whether there were adherence-based subgroups who benefitted most from treatment and whether, generally, adherence mattered. "The obvious answer is that, 'Of course it matters!' " said Choudhry. "These are evidence-based medications, and taking them must make a difference." Still, Choudhry said this isn't necessarily known.

In the present analysis, investigators assessed the relationship between adherence and secondary vascular/revascularization events following the index MI in patients randomized to full prescription coverage. Individuals were defined as adherent if they took the prescribed drugs at least 80% of the time during the six months after randomization. Patients were defined as partially adherent if they took their drugs 40% to 79% of the time and nonadherent if they took their drugs less than 40% of the time.

In addition, the researchers also evaluated the effect of adherence to more than one drug simultaneously to determine if adherence to all the drugs is needed to reduce cardiovascular outcomes.

When stratified by adherence, those with at least 80% adherence to all three study medications had a statistically significant 24% lower risk of having a major cardiac event or undergoing revascularization compared with individuals charged a copayment (controls). In contrast, partially adherent and nonadherent patients had no significant reduction in clinical outcomes vs the control arm.

Researchers note that partially adherent patients had an average adherence rate of 71% compared with 49% in the control arm, yet the risk of clinical events was equivalent.

Take All Your Medications

In assessing the incremental impact of adhering to each additional drug used in post-MI secondary prevention, adherence to each individual drug was beneficial in and of itself, said Choudhry. The benefit of treatment increased linearly with the number of drugs patients took, but only those who adhered to all three drug classes had outcome rates that were significantly lower than the control arm.

"As a clinician, the question we often ask—and I'm a rational prescriber, I believe they all have benefit—is whether one of the drugs is more important than the other," said Choudhry. "Or if pushed, which one is most important? I expected to see an effect with statin adherence, but not necessarily with ACE inhibitors. But lo and behold, that's not what we found."

The bottom line, said Choudhry, is that each drug is important, and "that the more you take, the better it is."

Research was supported by grants from Aetna and CVS Caremark to Brigham and Women's Hospital. Choudry has no conflicts of interest; disclosures for the coauthors are listed in the paper.



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