New low-cost daily pill containing four drugs can cut number of heart attacks and strokes by a third
Results from a clinical trial show that when compared with just lifestyle advice, taking the low-cost polypill reduced the risk of major cardiovascular events by 34%
Cardiovascular diseases are the number one cause of deaths globally. And, 85% of these deaths are due to heart attacks and strokes, according to the World Health Organization (WHO). A team of scientists now report that a four-in-one pill, if taken daily, is effective in reducing the risk of major cardiovascular events such as heart attack, stroke, and heart failure by more than a third over five years.
The low-cost polypill combines four cardiovascular drugs in a single pill - aspirin, a statin (atorvastatin) and two drugs to lower blood pressure (hydrochlorothiazide and enalapril).
The results of the clinical trial, published in The Lancet, shows that when compared with just lifestyle advice, taking the low-cost polypill reduced the risk of major cardiovascular events by 34%. Further, it reduced such events by around 40% in individuals without a history of cardiovascular disease, and by approximately 20% in those with a previous history of cardiovascular disease. Researchers say the effects were similar in both men and women and the old and young.
According to Professor Reza Malekzadeh from the Tehran University of Medical Sciences, Iran, who led the study, their research has shown a polypill prevents heart disease in a developing country and is an important step forward in preventing heart disease.
The research team says that if adopted correctly, it could substantially reduce the burden of cardiovascular disease, especially in low- and middle-income countries (LMICs). They add that it could also work in other countries, particularly those where cardiovascular diseases are still increasing.
“Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high, and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs,” says the study.
According to the WHO estimates, an estimated 17.9 million people died from cardiovascular diseases (CVDs) in 2016, representing 31% of all global deaths. Further, out of the 17 million premature deaths (under the age of 70) due to noncommunicable diseases in 2015, 82% were in low- and middle-income countries, and 37% are caused by CVDs.
The current study was led by Tehran University of Medical Sciences in Iran. Between February 22, 2011, and April 15, 2013, the researchers enrolled over 6838 individuals - aged 55 years or over, living in 236 villages in Northern Iran - into the study.
Villages were randomly divided into two groups. In 116 villages, 3,417 study participants were given general advice on diet, exercise, and smoking. In 120 villages, 3,421 participants were given the same advice on a healthy lifestyle and also a polypill to take every day. The team assessed whether the participants took the polypill, and how many major adverse clinical events (for example, heart attack, stroke, or death) they had over the next five years. The analysis shows that around 63% took the polypill as recommended (at least 70% of the time).
After five years, the findings show that 202 participants in the polypill villages had suffered from a heart attack or stroke as compared to 301 in the villages where only lifestyle advice was given.
“Compared with lifestyle advice, taking the polypill reduced the risk of major cardiovascular events by 34% overall. After adjusting for participants taking other cardiovascular drugs, the overall protective effect of the polypill was reduced to 22% (from 34%) but remained statistically significant. Systolic and diastolic blood pressure did not differ significantly between the groups, but LDL (low-density lipoproteins) cholesterol was significantly lower in polypill arm,” the findings state.
The results suggest that 35 individuals would need to be treated with the polypill to prevent one person from having a severe cardiovascular event. What is further significant is that participants who took the polypill as directed - at least 70% of the time - saw the most substantial protective effect against future cardiovascular events. The analysis shows in participants with high adherence to treatment, the number needed to treat was 21. According to the researchers, it reduced their risk by more than half (57%) compared with those who were only given lifestyle advice. The team, however, did not observe a corresponding improvement in blood pressure.
The researchers state that while a few people complained of dizziness, muscle pains or indigestion, these were “just as common in people who were taking or not taking the polypill.”
The polypill also seemed to be acceptable, with most people continuing to take it for all five years, they add.
“Those who took part in the study were typical middle-aged men and women from the villages. At the start of the study, most were aged under 65, one in 10 had heart disease, one in 10 had diabetes, and half had high blood pressure. This suggests that most people of the age group 55-65 years could take the polypill,” says the study.
According to experts, poor medication adherence is common among patients with cardiovascular disease, with research suggesting that around a third of patients stop taking their medication as early as 90 days after having a heart attack. The idea of combining several drugs in a single pill – the polypill – was initially proposed in 2001. Since then, several small, short-term studies in a number of countries have shown a polypill could reduce blood pressure and cholesterol levels. However, this is the first study with a large enough sample size and follow-up time to show that a polypill can prevent heart disease and strokes. “This is the largest trial confirming the value of the polypill and showing it is effective in primary prevention,” says the study.
The researchers add that while the idea of the polypill has always been appealing, the results demonstrate for the first time that a fixed-dose polypill can achieve clinical benefits in practice, and indicate that the “benefits of widespread polypill use outweigh any known side effects.”
“Previously, there had been concerns as to whether a polypill would be effective in those who had not already had cardiovascular disease, but this study shows that in high-risk populations, as in Iran, this approach is effective in preventing first and subsequent cardiovascular disease,” says Professor Neil Thomas from the University of Birmingham.