‘Polypill’ reduces cardiovascular mortality by 33% in patients treated after a heart attack

A three-drug medication known as a ‘polypill’ could become an integral part of global strategies to prevent adverse cardiovascular events.

A three-drug medication known as a “polypill,” developed by the Spanish National Center for Cardiovascular Research (CNIC) and Ferrer, is effective in preventing secondary adverse cardiovascular events in people who have previously had a heart attack, reducing cardiovascular mortality by 33% in this patient population. These are findings from the SECURE trial led by Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, and General Director of CNIC, the results of which have been published in The New England Journal of Medicine [1].

Longevity.Technology: The most important determinant of cardiovascular health is age [2] and the world’s population is getting older, with the number of older people projected to double to 1.5 billion in 2050 [3]. Cardiovascular disease (CVD) is set to result in 40% of all deaths and rank as the leading cause in people aged 60+ and the cost to treat cardiovascular disease is projected to triple [4], but a key risk factor in recurrent cardiovascular events is the lack of adherence to medication. Enter the polypill, which combines a variety of fixed-dose drugs, and encourages medication adherence.

“The results of the SECURE study show that for the first time that the polypill, which contains aspirin, ramipril, and atorvastatin, achieves clinically relevant reductions in the recurrent cardiovascular events among people who have recovered from a previous heart attack because of better adherence to this simplified approach with a simple polypill, rather than taking them separately as conventional,” said Dr Fuster [5].

Patients recovering from a heart attack – also known as myocardial infarction – are prescribed specific treatments to prevent subsequent cardiovascular events. Standard therapy includes three different drugs: an antiplatelet agent (such as aspirin); ramipril or a similar drug to control blood pressure; and a lipid-reducing drug, such as a statin. However, fewer than 50% of patients consistently adhere to their medication regimen.

“Although most patients initially adhere to treatment after an acute event such as an infarction, adherence drops off after the first few months,” explained Fuster. “Our goal was to have an impact right from the start, and most of the patients in the study began taking a simple polypill in the first week after having a heart attack [5].”

“Adherence to treatment after an acute myocardial infarction is essential for effective secondary prevention,” said José María Castellano, MD, study first author and Scientific Director of Fundación de Investigación HM Hospitales [5].

CNIC scientists first demonstrated that prescription of their polypill significantly improved treatment adherence among patients recovering after a myocardial infarction, in the FOCUS study, previously published in the Journal of the American College of Cardiology (JACC).

The CNIC team launched the SECURE study, an international randomised clinical trial, to determine whether the improved treatment adherence with the polypill translated into a reduction in cardiovascular events. The polypill analysed in the study, commercialised under the name Trinomia, contains aspirin (100 mg), the angiotensin-converting enzyme inhibitor ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg).

“The polypill, being a very simple strategy that combines three essential treatments for this type of patient, has proved its worth because the improved adherence means that these patients are receiving better treatment and therefore have a lower risk of recurrent cardiovascular events,” added Dr Castellano [5].

SECURE included 2,499 patients from seven European countries (Spain, Italy, Germany, the Czech Republic, France, Poland and Hungary) recovering after a heart attack. Study participants were randomly assigned to receive standard therapy or the CNIC polypill. The average age of the participants was 76 years, and 31% were women. The study population included 77.9% with hypertension, 57.4% with diabetes, and 51.3% with a history of smoking tobacco.

Researchers analysed the incidence of four major cardiovascular events: death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, and need for emergency coronary revascularisation (the restoration of blood flow through a blocked coronary artery). The study followed patients for an average of three years and produced conclusive results: patients taking the CNIC polypills had a 24% lower risk of these four events than patients taking the three separate drugs.

The stand-out finding of the study is the effect of the polypill on the key outcome of cardiovascular-related death, which showed a relative reduction of 33%, from 71 patients in the group receiving standard treatment to just 48 in the polypill group [1].

Importantly, the study found that patients in the polypill group had a higher level of treatment adherence than those in the control group, thus confirming the findings of the earlier FOCUS study, and in part such good adherence appears to explain the benefits of the simple polypill.

“The 33% reduction in cardiovascular mortality demonstrates the efficacy of treatment with Trinomia compared to standard treatment,” explained Oscar Pérez, Chief Marketing, Market Access and Business Development Officer at Ferrer. “These results ratify our purpose of making a positive impact in society and represent an important step in our mission to provide significant and differential value to people who suffer from serious health conditions [5].”

“The SECURE study findings suggest that the polypill could become an integral element of strategies to prevent recurrent cardiovascular events in patients who have had a heart attack,” added Fuster. “By simplifying treatment and improving adherence, this approach has the potential to reduce the risk of recurrent cardiovascular disease and death on a global scale [5].”

[1] https://www.nejm.org/doi/10.1056/NEJMoa2208275
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366686/
[3] https://www.un.org/en/development/desa/population/publications/pdf/ageing/
[4] https://pubmed.ncbi.nlm.nih.gov/21262990/
[5] https://www.mountsinai.org/about/newsroom/2022/polypill

Photograph: Jakarin/Vectorstock