Can a low-cost polypill prevent cardiovascular disease in emerging markets?

Cardiovascular system and disease:

With about 100,000 kilometers of total blood vessel length, our cardiovascular system has a long way to go to perform the vital task of supplying each and every cell of the body with enough nutrients and oxygen at any given time. In doing so, the artery, with the exception of the pulmonary artery, and the arteriole (i.e. its branches) transport oxygen-rich blood from the left ventricle to the individual body tissues. Oxygen exchange takes place in the permeable capillaries, which form the transition between arteries and veins. Accordingly, the veins and venules (i.e. their branches) transport the oxygen- and nutrient-poor blood back to the right atrium of the human heart.

Cardiovascular diseases can be fatal - because they are among the most common diseases globally and are also by far the most common cause of death in Austria. The main cause of such diseases is arteriosclerosis (i.e. narrowing and calcification of blood vessels). Among others, cardiovascular diseases include: Angina pectoris (i.e. heart stenosis), high blood pressure, heart attack, heart failure (i.e. heart weakness) and stroke. Both external risk factors such as lack of exercise, smoking, obesity or stress, as well as the patient's own genetic factors, influence each other and are related to the function of the heart and its blood vessels.

Cost-effective help?

Some risk factors, such as high blood pressure or diabetes, can be treated with the help of medication. However, these can be a barrier in certain regions due to high costs or poor healthcare. A study has therefore investigated whether a so-called polypill, which combines several active ingredients in one capsule as effectively as possible, can be used to reduce the number of cardiovascular diseases. Since this could be taken inexpensively and without prior medical examinations by the older population, emerging countries in particular are showing great interest in it.

Study Method:

The randomized, placebo-controlled study published in 2020, in the New England Journal of Medicine, examined the effect of a polypill. This consists of one part cholesterol-lowering drug and three parts antihypertensive drug. The additional administration of acetylsalicylic acid (ASA for short) was intended to enhance the effect without producing an increase in the risk of bleeding.

A total of 6,714 people from nine countries around the world participated, with nearly 90% from India, Indonesia, Malaysia, Bangladesh or the Philippines. The average age was 63.9 years and the majority recorded cardiovascular risk factors, with 83.8% of participants having high blood pressure (or hypertension) and 36.7 being diagnosed with type 2 diabetes or high blood sugar. With an average level of 120.7 mg/dl LDL cholesterol was also elevated. For about 4.6 years, the study participants took one tablet daily. The three divided groups each received:

• Group 1: Polypill containing 40 mg simvastatin, 100 mg atenolol, 25 mg hydrochlorothiazide and 10 mg ramipril (- or placebo).
• Group 2: Polypill as in the first group with additional 75 mg ASA (- or double placebo)
• Group 3: ASA only (- or placebo)

The primary endpoint was the occurrence of cardiovascular disease or cardiovascular death.

Significant results?

According to the results, the primary endpoint in group 1 was seen in 126 participants (4.4%), while the comparative control group (i.e., placebo) noted it in 157 participants (5.5%). Compared to the placebo group, this represents a 21% reduction. In the group with the combination therapy polypill and ASA the effect increases: compared to the placebo group (83 participants with 5.8%) the primary endpoint occurs in 59 study participants (4.1%). With 31%, the reduction is higher in this group. In the last study group, which took only ASA, the primary endpoint occurred in 116 participants (4.1%) and in the comparative placebo group in 134 participants (4.7%). Due to the low dose of ASA, this did not lead to any severe bleeding according to the study.

Conclusion:

The study showed a reduction in cardiovascular events in the study groups taking a combination of three antihypertensives and a cholesterol-lowering agent. Additional reductions in these primary endpoints were seen with the addition of ASA. Such lower-cost combination therapy could potentially provide significant benefits for cardiovascular disease prevention in emerging countries.

Active ingredients: