When applied to a different purpose, an old concept can sometimes be more successful than for what it was initially developed. The results of the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) clinical trial released in the second half of 2022 in the New England Journal of Medicine demonstrate just how effective this strategy, when executed well, can be in cardiovascular drug development. This article will explore the latest in cardiovascular drug development, specifically the potential of the polypill, and touch on what a cardiology CRO’s role is.
What is a Polypill?
The polypill, a combination of cardiovascular drugs, is a topic that has been visited several times in the cardiovascular field after it was initially proposed in an article published in the British Medical Journal in 2003. The idea of the polypill has historically been applied to creating a strategy for the primary prevention of cardiovascular diseases.
Previous trials studying the effects of a polypill for primary prevention have included:
- The TIPS-3 trial, which used a combination of simvastatin, atenolol, hydrochlorothiazide, and ramipril.
- The PolyIran trial was a cluster randomized trial that used two formulations of the polypill that included a combination of aspirin, atorvastatin, hydrochlorothiazide, and enalapril or the combination of aspirin, atorvastatin, hydrochlorothiazide, and valsartan.
- The HOPE-3 trial used a combination of rosuvastatin, candesartan, and hydrochlorothiazide.
- The PARADIGM-HF trial used a combination of sacubitril and valsartan for heart failure patients.
However, the use of polypills for primary prevention has been met with criticism. The use of polypharmacy in primary prevention is not recommended, especially as there is little benefit to the risk of side effects of the medications in those who do not meet the criteria for treatment with these drugs individually.
What is the SECURE Trial and its Implications in Cardiovascular Clinical Practice?
The SECURE trial is a Phase III, randomized clinical trial studying the effect of a polypill containing aspirin, simvastatin, and ramipril as secondary prevention in cardiovascular disease.
Previous research shows that complex dosing reduces cardiovascular medication adherence, and sufficient adherence is needed to ensure improved outcomes. The SECURE trial hypothesized that a polypill using the medications already recommended for secondary prevention would increase adherence and reduce the risk of poor outcomes from cardiovascular disease.
Unlike previous clinical trials, several polypill formulations were used containing different doses of ramipril and atorvastatin, allowing greater flexibility. The trial was conducted over seven European countries and recruited 2499 participants with a follow-up period between 2-5 years.
The inclusion criteria comprised patients who were diagnosed with a type 1 MI in the last six months and were older than 75 years-of-age, or at least 65 years old with at least one of the following risk factors:
- Diabetes mellitus.
- Mild to moderate kidney dysfunction.
- History of previous MI (over 6 months ago).
- History of prior stroke.
- Previous coronary revascularization or coronary artery bypass grafting (CABG).
The primary endpoints were cardiovascular death, nonfatal MI, nonfatal ischemic stroke, and urgent coronary revascularization.
At the median trial follow-up point of 36 months, the composite of the four primary endpoints had occurred in 118 participants in the polypill group (9.5%) and 156 in the standard of care group (12.7%). Hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.60–0.96; p<0.001 for non-inferiority, p=0.02 for superiority.
The trial results also showed better adherence at six months for the polypill group (70.6%) than for those receiving standard-of-care treatment (62.7%). And at 24 months, the gap had widened further, with 74.1 % of the polypill group adhering to the treatment regimen versus 63.2 receiving the usual care.
The SECURE trial demonstrates how the polypill can improve cardiovascular outcomes in patients who have had a myocardial infarction.
The use of polypills in practice could not only benefit the patients from an increase in adherence from the convenience of having one pill but combining these medications may also lower costs for patients making it more affordable and accessible.
The trial has allowed for further research using the polypill concept for other indications.
Limitations of the Polypill
While the results of the SECURE trial show a clear benefit in the polypill group, the results do not clearly illustrate the reason. Using data from previous analyses of the effect of adherence on cardiovascular outcomes, one can deduce that it would have impacted the results. However, the positive findings may also have been influenced by other factors, such as the pleiotropic effects of the medications.
Other limitations of the trial include the generalizability of the clinical trial. There are still differences in lifestyle, racial demographics, and other risk factors within the European and North American populations, which may result in differences in outcomes and adverse effects with the use of the polypill. More research and trials within the United States may be necessary before the polypill can be approved by the FDA and introduced into clinical practice.
Drug Development in Cardiology
The development of the polypill in cardiology is an exciting advancement that has the potential to improve cardiovascular outcomes while providing a simpler and more cost-effective solution for patients to adhere to their treatment regimens. The success of the polypill in the SECURE trial is a promising example of how repurposing an old concept for new indications can lead to practice-changing results. This breakthrough has also opened the door for further research, applying this concept to other indications and specific high-risk populations for primary prevention. As we continue to explore new solutions in cardiovascular drug development, the polypill represents an important step forward in the fight against cardiovascular disease.
A Cardiology CRO’s Role in Drug Development
Looking to make a breakthrough in the cardiovascular drug development space? Look no further than Vial Cardiology CRO. Our team of experts is dedicated to making the drug development process easier and more efficient, increasing your chance of success. By utilizing a full-service tech-driven approach, we integrate eSource, EDC, and ePRO into one system, streamlining the clinical trial process and reducing the overall cost.
Our state-of-the-art technology platform is designed to improve efficiency and accuracy, ensuring that your Phase I, Phase II, or Phase III trials run smoothly and on time. Our team of experienced ClinOps professionals will work closely with you to design a customized plan that meets your specific needs, providing support every step of the way.
Don’t let the cardiovascular drug development process slow you down. Contact one of our team members today to learn how Vial Cardiology CRO can help you run faster, more efficient, and affordable cardiology clinical trials. With Vial Cardiology CRO by your side, you can be confident in the success of your drug development program.
