The research and medical communities are slow to undertake work on combination therapies. Regulation makes it exceedingly expensive to assess multiple combinations, and there are numerous other perverse incentives to challenge any effort to build combination therapies with components developed and manufactured by different groups. Short of working around the existing system of regulation, and methods of doing this at scale are lacking at the present time, this is a challenging problem to solve. People follow incentives. Given this, it it is entirely plausible that there are many largely unexplored instances in which existing classes of medication for age-related disease might synergize to be more effective together.
In this context, clinicians and researchers have been discussing polypills for quite some time. The term polypill usually means a combination of existing treatments for cardiovascular disease such as statins to reduce blood cholesterol, ACE inhibitors to lower blood pressure, diuretics to reduce fluid retention, and so forth. The data to date strongly suggests that many reasonable polypill combinations will improve upon single medication use, and possibly do so at lower overall doses, and thus with lower side-effects.
Here, researchers report on a recent large clinical trial of a polypill, carried out in a comparatively poor population who are largely without access to the panoply of medications available in wealthier regions. The effect size is about what one would expect: in the world of the immediate past in which no-one was trying to tackle the causes of aging, and thus comparatively little can be achieved, reductions in blood cholesterol and blood pressure have been outstanding successes. Reducing cardiovascular mortality by a third without in any way addressing the underlying causes of cardiovascular mortality is quite the feat. In the immediate future, when senolytic drugs and other therapies that do address the causes of aging start to become widely used, we should expect to see much larger beneficial changes in population health.
A daily pill containing four medicines can cut the number of heart attacks and strokes by a third, a study shows. The polypill contains blood-thinning aspirin, a cholesterol-lowering statin, and two drugs to lower blood pressure. The researchers said the pill had a huge impact but cost just pennies a day. They suggest giving it to everyone over a certain age in poorer countries, where doctors have fewer options and are less able to assess individuals.
The study was based in more than 100 villages in Iran and about 6,800 people took part. Half the people were given the polypill and advice on how to improve their lifestyle, with the other half just getting the advice. After five years there were 202 major cardiovascular events in the 3,421 people getting the polypill and 301 in the 3,417 not getting the pill. The polypill led to large reductions in bad cholesterol but had only a slight effect on blood pressure, the study showed. The drug was given to people over the age of 50 whether they had had a previous heart problem or not.
In the UK and other wealthier countries doctors have the time to assess the needs of individual patients and a wide choice of different drugs, such as statins, to chose from. "In the UK, the advantages would be more marginal and you would probably want a clinical trial to see any benefits over what is offered at the moment."
The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50,045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation.
The non-pharmacological preventive interventions (including educational training about healthy lifestyle - eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome - occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke) - was centrally assessed by the GCS follow-up team.
We enrolled 6838 individuals into the study - 3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. During follow-up, 301 (8.8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5.9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0.66). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0.43). The frequency of adverse events was similar between the two study groups.