A polypill for secondary cardiovascular prevention?

By Joe Hannan | Medically reviewed by James Beckerman, MD, FACC
Published December 9, 2022

Key Takeaways

  • A study demonstrated that patients who were prescribed a polypill containing aspirin, ramipril, and atorvastatin had fewer subsequent cardiac events after initial myocardial infarction compared with patients who were prescribed separate pills.

  • Another study showed that elderly people are at increased risk of failing to comply with medication regimens.

  • Such findings shed light on how simplifying medication regimens may improve patient adherence and help them avoid adverse outcomes.

“Take your meds.” It’s simple guidance, spelled out in black and white on the pill bottles and accompanying literature—yet many patients fail to follow it, with devastating results.

To help address this problem, a study published in the New England Journal of Medicine (NEJM) investigated a new approach to medication adherence.[]

Researchers said it led to fewer cardiac events following myocardial infarction and may help in ensuring the accurate administering of medications to patients.

Inside the study

It’s a solution that’s somewhat ingenious in its simplicity: What if instead of telling patients with myocardial infarctions to take three pills, physicians told them to take one? How might that affect adherence to their prescription drug regimens?

A team of researchers set out to explore these questions in an international, randomized, controlled phase 3 clinical trial, the results of which were published in the NEJM in September 2022.

The study involved 2,499 patients, all of whom had a myocardial infarction within the previous 6 months. All patients were either older than 75 or were at least 65 with another risk factor, such as diabetes, kidney dysfunction, or previous myocardial infarction, among others.

Following myocardial infarction, patients often are prescribed a cocktail of aspirin, ramipril, and atorvastatin, according to research published by the Journal of Clinical Medicine.[]

Aspirin helps ward off future blood clots, ace inhibitors like ramipril dilate blood vessels and ease strain on the heart, and atorvastatin helps bring LDL levels into a normal range, according to the American Heart Association.[] For some patients, taking three (or more) pills per day is a lot to remember.

In the trial, the investigational group received a polypill—a single pill that contained 100 mg of aspirin; 2.5 mg, 5 mg, or 10 mg of ramipril; and 20 mg or 40 mg of atorvastatin. The control group received the usual care.

Researchers monitored study participants for a median of 36 months, tracking the following primary composite outcome events: cardiovascular deaths, nonfatal type 1 myocardial infarctions, nonfatal ischemic strokes, or urgent revascularizations.

In the polypill group, 118 of 1,237 (9.5%) experienced a primary-outcome event, compared with 156 of 1,229 (12.7%) in the usual care group.

Researchers also tracked secondary endpoints: a composite of cardiovascular fatalities, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. Key secondary events occurred in 8.2% of the polypill recipients and 11.7% of the usual-care recipients.

"Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care."

Castellano et al., NEJM

Adherence challenges

At the heart of this trial was the challenge of patient adherence to medication. A study published in Scientific Reports in 2020 illustrated the extent of this problem in post-myocardial infarction care.[]

Researchers tracked medication adherence among 225 patients who had experienced a myocardial infarction. They considered patients compliant with medication guidance if, within a year after discharge from the hospital, they had filled their prescriptions at least 80% of the time.

The researchers tracked adherence for ACE inhibitors, P2Y12 receptor inhibitors, and statins. Aspirin was not tracked because it is not a reimbursable drug. Across all three groups of medications, adherence was 64.1% (± 24.5%).

Adherence for the individual drug groups was as follows:

  • ACE inhibitors: 67.2% (± 31.8%)

  • P2Y12 receptor inhibitors: 61.6% (± 34.2%)

  • Statins: 64.4% (± 32.1%)

Complicating matters, adherence worsened over time. In the first quarter after discharge, 36.7% of patients were adherent to all three medications 80% or more of the time. By the fourth quarter, the percentage of adherent patients dropped to 16.7%. Also, in Q1, 16.1% of patients were taking none of their meds. This rose to 40% by Q4.

"Adherence to pharmacotherapy after myocardial infarction decreases over time in [a] similar manner for all pivotal groups of drugs prescribed after MI."

Pietrzykowsk et al., Scientific Reports

The researchers added that their investigation demonstrated that people who are elderly, less educated, or living alone, or people who have received a coronary artery bypass graft, required “additional educational and motivational efforts” to promote adherence to maintenance meds after discharge.

Related: Challenging conventional wisdom: AFib and the sexes

Simplifying treatment complexity

According to the NEJM study, which focused on the elderly, using polypills after myocardial infarction may also improve compliance and reduce risks of subsequent cardiac events.

“The use of a cardiovascular polypill as a substitute for several separate cardiovascular drugs could be an integral part of an effective secondary prevention strategy,” the researchers wrote, highlighting a key finding for this at-risk group of patients.

"By simplifying treatment complexity and improving availability, the use of a polypill is a widely applicable strategy to improve accessibility and adherence to treatment, thus decreasing the risk of recurrent disease and cardiovascular death."

Castellano et al., NEJM

What this means for you

As of the end of 2022, this polypill is not available to US physicians. Doctors can stay abreast of FDA approvals to monitor the pill’s status. Regardless of whether the drug is approved, this research raises some interesting observations about how simplicity might improve patient adherence to prescription drug regimens.

Read Next: Polypill strategy reduces the risk of cardiovascular events after a myocardial infarction
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