Improved Adherence to Medical Therapy Reduces CVD Events in Secondary Prevention Patients

Patients hospitalized for MI or chronic atherosclerotic disease who adhere to guideline-based medical therapy have a significantly lower risk of major adverse cardiovascular events when compared with individuals only partially adherent or nonadherent to medical therapy, a new study has shown.

In addition, sticking with guideline-recommended therapy, which includes statins and ACE inhibitors, was associated with significantly reduced per-patient medical costs, according to investigators.

“Cardiovascular disease, including atherosclerosis and acute coronary syndrome, is obviously a huge problem for the US and the rest of the world,” lead investigator Sameer Bansilal (Icahn School of Medicine at Mount Sinai, New York, NY) told TCTMD. “The medication adherence piece of the puzzle is really a big part of us not being able to implement what we already know. We’re always on the lookout for the ‘new and exciting’ when the fact of the matter is we’ve done a very poor job implementing what we already know works.”

The use of evidence-based and guideline-recommended medical therapies for secondary prevention of cardiovascular disease is estimated to be responsible for at least half of the overall 50% reduction in death from cardiovascular disease over the past 20 years, according to investigators. This reduction has been achieved despite patients not adhering to their prescribed drug regimens.

In some registries, nearly one third of secondary-prevention patients, including post-MI patients, are no longer taking their medication at 1 year. “You’d imagine that people who had a heart attack or underwent coronary revascularization would be motivated to take their pills to prevent them from being hospitalized again,” said Bansilal. “It really is a case of out of sight and out of mind after the first year. By the second year, more than half of patients aren’t taking their pills. And even for the other half that are [taking their medication], there is a significant gradient in terms of people taking the pills the right way.”

The ease and success of coronary revascularization today has somewhat minimized the seriousness of MI, added Bansilal. “Twenty-five years ago, it was a big deal, in hospital for a week, with CABG being a big intervention,” he said. “Now, with a radial intervention, you’re walking around 2 hours later, home the next day, and mowing the lawn by the weekend.”

More Than 25% Nonadherent at 2 Years

The study, published August 15, 2017 in the Journal of the American College of Cardiology, is an analysis of medical and pharmaceutical claims from patients enrolled in the Aetna insurance and Medicare Advantage databases, both of which allow for tracking of use of healthcare resources and clinical outcomes over time.

Adherence was estimated by calculating the proportion of days covered (PDC) for statins and ACE inhibitors after the index date. A patient with a PDC ≥ 80% is considered adherent, while a PDC between 40% and 79% is considered partially adherent and less than 40% is classified nonadherent.

In total, 4,015 patients hospitalized for an MI and 12,976 patients hospitalized for atherosclerosis were included in the analysis. In the post-MI cohort, 26% of patients were nonadherent to medical therapy, 31% were partially adherent, and 43% were fully adherent. Similarly, in the atherosclerosis cohort, 28%, 38%, and 34% were classified as nonadherent, partially adherent, and fully adherent.

In the post-MI patients, those fully adherent to statin and ACE inhibitor therapy had a 27% lower risk of major adverse cardiovascular events—defined as all-cause mortality, hospitalization for nonfatal MI or stroke, or coronary revascularization—at 2 years compared with nonadherent patients (18.9% vs 26.3%; P=0.0004). Similarly, individuals fully adherent to medical therapy had a 19% lower risk of cardiovascular events compared with those who took their medication only some of the time (18.9% vs 24.7%; P=0.02). There was no difference in clinical outcomes between nonadherent and partially adherent groups.

For those patients hospitalized for atherosclerosis, fully adhering to medical therapy after discharge was also associated with a 44% lower risk of major cardiovascular events at 2 years when compared with those considered nonadherent to treatment (8.4% vs 17.2%; P<0.0001). Compared with patients who took their medication only part of the time, those who adhered to treatment had a 24% lower risk of cardiovascular events (8.4% vs 12.2%; P<0.0001). Partially adhering to statin and ACE inhibitor therapy was associated with a lower risk of clinical outcomes compared with those considered nonadherent.

To TCTMD, Bansilal said that statin and ACE inhibitor therapy have extremely solid data supporting their use in the chronic atherosclerosis and post-MI patient populations. “We want to chip away at improving adherence rather than look for another drug that reduces the risk of cardiovascular events by maybe another couple of percentage points—in absolute terms, maybe a percentage point—because these drugs if taking correctly can make a large absolute difference” in reducing cardiovascular events.

In the present study, aspirin adherence was not studied as the drug is primarily obtained over-the-counter and can’t be reliably measured in an insurance claims database, say researchers.

In addition to assessing the impact of adherence on cardiovascular outcomes, the researchers observed a significant reduction in medical costs among fully adherent patients. In the post-MI patients, full adherence to statins and ACE inhibitor therapy was associated with reduced per-patient annual direct medical costs compared with partial and nonadherence. Similar reductions were observed in the atherosclerosis cohort.

In an editorial, Paul Armstrong, MD, and Finlay McAlister, MD (University of Alberta, Edmonton) point out that “care gap” has been well documented in the GRACE, REACH, and CRUSADE registries, with the latest report underscoring the missed opportunities in treating patients with documented cardiovascular disease. This latest study might even underestimate nonadherence as it fails to account for patients who fail to even fill their first prescription after hospitalization, they add.

Financial Impact of Not Taking Medication

Regarding the abysmal adherence rates observed in this study, as well as others, Bansilal said there is no magic bullet that will alter patient behavior. The advent of the polypill might help with patient adherence, as could the increased use of extended provider/nonmedical personnel. Technology, which would include everything from daily text messages, talking pill bottles, and microchip-containing pills for easier tracking, is also being employed in the adherence battle.

Still, Bansilal believes that while no one effort is going to be the “Holy Grail,” any small improvement in adherence will have an “extremely high yield.”

He told TCTMD that intervening early, particularly in the first visit post-hospitalization, is critical. “In fact, it should really start from the bedside in terms of impressing upon patients the impact of taking their medication religiously,” he said. In the first visit with the cardiologist, which usually occurs within 6 weeks, patients are willing to listen and take direction. Once beyond the first three months, especially for some of the patients who have received a stent, the event is often in their rearview mirror and they are less susceptible to physician messaging.  

In their editorial, Armstrong and McAlister add that the frequency of physician follow-up and provider continuity are positively correlated with better patient adherence. Yet “despite the key relationship between patient adherence and both the effectiveness and efficiency of health care, a recent survey showed that roughly two-thirds of cardiac patients reported not discussing adherence with their cardiologist.” In addition, almost none of the physicians were able to identify the nonadherent patients.

“Thus, as a bare minimum, our first step as clinicians must be to routinely ask about adherence with all of our patients at every visit and to encourage them to take their medications as instructed,” write the editorialists.





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Michael O’Riordan is the Associate Managing Editor for TCTMD and a Senior Journalist. He completed his undergraduate degrees at Queen’s…

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  • Bansilal S, Castellano JM, Garrido E, et al. Assessing the impact of medication adherence on long-term cardiovascular outcomes. J Am Coll Cardiol 2016; 68:789-801.

  • Armstrong PW, McAlister FA. Searching for adherence: can we fulfill the promise of evidence-based medicine. J Am Coll Cardiol 2016; 68:802-804.

  • Bansilal, Armstrong, and McAlister report no conflicts of interest.