New findings of a meta-analysis of the largest clinical trial studies on polypill in an international study, indicated " Polypill with Aspirin" combination therapy, halve the risk of major cardiovascular events, without serious complications of aspirin.

Writer :Fereshteh Hashemi
Pubilshed Aug. 29, 2021
https://en.ddri.ir

 

According to the Digestive Diseases Research Institute (DDRI) of Tehran University of Medical Sciences (TUMS) based on the results of the study entitled "Effect of combined polypill, with and without aspirin on primary prevention of major cardiovascular events" ,conducted by scientists from Iran and Canada in collaboration with scientists from 13 other countries  and  published in  The Lancet (August 29 ,2021) "Polypill with Aspirin" combination therapy ,was effective in preventing primary cardiovascular outcomes by 47%, myocardial infarction (MI) by 53%, stroke by 51%, revascularization by 61% and cardiovascular death by 49%.

These important findings have been achieved while about 80% of cardiovascular events occur in individuals without a prior CVD

This study is the result of meta-analysis of three large clinical trial studies on the effect of "Polypill with or without Aspirin" on primary CVD outcome in individuals without a prior CVD.

 
One of these studies, is the "PolyIran" study, entitled: "Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomized trial" which was conducted in Iran by a team of researchers led by professor Reza Malekzadeh, Distinguished professor of Tehran University of Medical Sciences (TUMS).

 

The results of this study with 12000 participants which was published in The Lancet in 2019 , showed a 34% reduction in major cardiovascular events in people with or without a prior history of cardiovascular disease with "Polypill with Aspirin" combination therapy, which increased to 57% in participants with high adherence.

 
Two other studies were conducted by the research team in Canada with collaboration of scientists from 10 other countries led by professor Salim Yusuf, Distinguished professor of McMaster University, and the results were published in the New England Journal of Medicine. The first study by the research team showed a 39% reduction in cardiovascular events with a polypill treatment strategy. The second study of this research team, conducted on 5,713 participants from nine countries with 4.5 years follow up, found that the " Polypill with Aspirin" treatment strategy caused a 31% reduction in primary CVD outcome in people without a history of cardiovascular disease.

The concept of a combination pill was first proposed exactly 20 years ago as a strategy to substantially reduce CVD in the population and also in those who already have had a previous heart attack or stroke.

According to Professor Reza Malekzadeh, Distinguished professor of Tehran University of Medical Sciences (TUMS) and founder and the lead investigator of the  "PolyIran" study and senior author of this meta-analysis study : “ despite these three large and lengthy clinical trials, the  effect of polypill on the primary prevention of cardiovascular events in People with no history of major cardiovascular event, the inclusion of aspirin in polypill has been questioned by some studies and cardiologists because of concerns about the side effects of aspirin. Therefore, we specifically examined the " Polypill with Aspirin" treatment strategy in a meta-analysis of the results of three clinical trial studies on 18,162 participants from 26 countries who were followed for 5 years to provide robust answers to these two important questions:Should aspirin also be part of primary prevention of major cardiovascular events and check for efficacy and possible adverse events of Polypill with aspirin as compared to polypill without aspirin.

In this meta-analysis, mean age of the study population was 63 years, 9038 (49·8%) were female, 9746 (53·7%) had hypertension, 3061 (16·9%) had diabetes, and 4243 (23·4%) had a history of smoking. Mean SBP in the overall population was 137·7 and mean LDL was 121·7 mg/dl.

The main treatment strategy to evaluate effect of polypill on primary prevention of cardiovascular events in this meta-analysis was polypill included: two antihypertensive drugs, a statin with or without aspirin.

Participants were divided into treatment intervention groups:   "Polypill with Aspirin ", " Polypill without aspirin" and the control group) who receive either placebo or minimal care which include blood pressure control and healthy lifestyle advocacy)

 

 

Significant effects of the " Polypill with Aspirin ": from a 49% reduction in cardiovascular death to 61% reduction in revascularization!

Professor Malekzadeh says: “ The findings of the intervention in "polypill with aspirin" treatment arm, showed reduction of the primary  outcome by 47%, myocardial infarction  by 53% , stroke by 51% , revascularization by 61% and CV death by 49% .”

Robust scientific evidence for more efficacy and no serious adverse outcome in the " Polypill with aspirin”combination therapy

 
 

He adds: “The results of this study provide the strongest scientific evidence that the "Polypill with aspirin" treatment strategy, in addition to significant benefits in primary prevention of major cardiovascular events, is well tolerated. No significant differences in adverse events rate were observed in the intervention group polyill with aspirin compared to polypill without aspirin and the benefits of consumption "polypill with aspirin" increase as the duration of Consumption increase. ”

 

80% of CVD events in a community occurs in people who never had history of CVD

Professor Salim Yusuf, Distinguished University Professor at McMaster, executive director of the PHRI (The Population Health Research Institute) and the Principal Investigator of this meta-analysis study, said: “The findings are important in showing that this combination of drugs can halve the risk of future serious cardiovascular event in those who did not previously have any evidence of CVD. Given that 80% of CVD in a community occurs in those who never had history of CVD, this provides a simple, low cost and effective strategy to reduce the risk of CVD in general populations in the world.”

He added  : “These results are huge, and its wide use can avoid between 5 and 10 million individuals experiencing a stroke, heart attack or dying from these conditions yearly,”

Professor Yusuf emphasizes:  “This strategy is effective to reduce the global burden of CVD and facilitate achieving the Sustainable Development Goal (SDG) of reducing premature CVD mortality by 30% by 2030. ”

 
Dr. Philip Joseph, cardiologist , associate professor of medicine at McMaster University and first author of this metanalysis  study says: “The findings showed that the " polypill with or without aspirin" treatment strategy  also resulted in a 38% proportional reduction in the primary CVD outcome , 46% reduction in revascularization and a 35% reduction in CV death. ”

He added: “ For " polypill   without aspirin"  treatment strategy  (Fix dose combination  therapies with only lipid and BP lowering drugs), there was a 32% proportional reduction in the primary outcome, 41% reduction in MI, 38% reduction in stroke, 45% reduction in revascularization, and 27% reduction in CV deaths. ”


According to Dr Joseph, “ the effects of " polypill with aspirin " treatment strategy in preventing cardiovascular events are the same for people with "different levels of blood lipids, blood pressure and other risk factors" and "with or without cardiovascular risk factors. ”

He says: “Our new study showed that the highest benefit of " polypill with aspirin " treatment strategy in major cardiovascular events was related to revascularization (61%), myocardial infarction (53%), stroke (51%), respectively, and among age groups, more benefit has been observed for people 60 years and older. ”


 Dr. Gholamreza Roshandel, Epidemiologist ,Associate Professor of Golestan University of Medical Sciences (GOUMS) and the second author of this meta-analysis said: “The effect of "Polypill with aspirin" treatment strategy in the initial prevention of cardiovascular events and myocardial infarction and stroke, which is significant for all different ages of the study population, has more benefits for the elderly and  further reduces the risk of major cardiovascular events.”

He says: “ The greatest benefit of the " polypill with or without aspirin" treatment strategy is for populations at moderate to severe risk of major cardiovascular event. ”

The results of this study, were welcomed by international leaders in cardiovascular research.

The demonstration of a low-cost approach using fixed dose combinations to reduce CVD by about 50 per cent is extraordinary !

Professor Fausto Pinto ,WHF(The World Heart Federation) president said : “The World Heart Federation (WHF) is committed to promoting cardiovascular health for everyone by reducing the CVD burden worldwide, in both developed and developing countries.The demonstration of a low-cost approach using fixed dose combinations to reduce CVD by about 50 per cent is extraordinary and represents a huge opportunity to tackle the condition globally, with a major potential impact on people's lives. The WHF has supported the use of a polypill for the last decade and these results provide robust evidence to strengthen our global advocacy strategy.”

 

Could PolyPill serve as a global strategy for preventing myocardial infarction and stroke specially in low and middle income countries?

 Cardiovascular diseases kill 19 million people each year and twice as many experience heart attacks or strokes every year. Also the number of years lost due to disabilities due to cardiovascular diseases has increased by 16% in the past decade. The share of low and middle-income countries in the premature death due to CVD is 80%.

According to international researchers, with the current trend, achieving the goal of "reducing premature deaths caused by cardiovascular diseases to one third in the world by 2030" would not be possible.

 

Half of Iran's population does not see the age of 70 years!

According to Professor Malekzadeh  “  The incidence of premature (under 70 years of age) and very premature (under 50 years of age) deaths in Iran is much more worrying. Half of Iran's 83 million population does not reach the age of 70 and die prematurely. Of Iran's 380,000 annual deaths in 2017, about half (47%) of them are under 70 years of age and premature. ”

Cardiovascular diseases and myocardial infarction account for half of all premature deaths in Iran, and the age of myocardial infarction in Iran is 10 years below the average age of European countries.

 

Who can use "PolyPill"?

The best strategy for prevention of CVD and premature morbidity and mortality is of course healthy lifestyle specially exercise, healthy food intake low salt and weight loss in obese and overweight individuals. Polypill should always be combined with healthy life style.

"PolyPill" is effective for people older than 50 year of age specially as primary prevention. For primary prevention in people who have at least one CVD risk factor (hypertension, elevated lipid level, diabetes, smoking, opium, obesity and sedentary life) and those with a medium risk of CVD (>10% in 10 year) the regular daily intake of one tablet reduces the risk of cardiovascular attacks close to 50%.

Polypill can of course be used for secondary prevention of CVD (those who have past history of coronary heart disease, myocardial infarction or stroke). In secondary prevention patients may need addition drug(s) based on recommendation of their physician.

Polypill should not be used in patients who have allergy to one or more components of it. The most common side effects are dizziness and muscle cramps which may subside after few weeks of drug intake.

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