A new study from Beth Israel Deaconess Medical Center (BIDMC) has proved the cost-effectiveness and life-saving potential of the “polypill”: a single new pill which combines four commonly prescribed cardiovascular drugs into one to prevent a recurrent stroke or heart event in adult patients in low- and middle-income countries (LMIC).
The researchers found an extremely promising result: the polypill could provide the highest returns on investment in terms of health and cost savings of any broadly applied cardiovascular intervention that is part of standard care in these countries.
Across the world, a staggering percentage of disease and death is caused by heart disease and stroke. In LMICs especially, where over 75% of these events occur, in patients almost ten years younger, on average, than in more prosperous regions, cardiovascular disease (CVD) typically kills, incapacitates or severely reduces the quality of life (QoL).
Evidence-based medical guidelines show that just four types of drugs, namely, aspirin, a statin, an angiotensin converting-enzyme (ACE)-inhibitor, and a beta blocker, reduce the chances of recurrence of these conditions (called “secondary prevention”), reduce death rates due to CVD and improve the Quality of Life (QoL). The primary obstacles to their use appear to be poor availability of care, poor prescription practices as well as the cost and difficulty of taking all four separately. As a result of these roadblocks, only one in four patients in LMICs who should be taking these medications actually do so.
Though several polypill formulations are available, they have not come into widespread use, partly because they have not been proved to be cost-effective. The current study aims to address this issue.
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How was the study done?
The current study used a detailed mathematical model to simulate the population subset with a history of stroke or heart attack, in five LMICs that cover the spectrum of economic development and also have high rates of cardiovascular disease (CVD). Data on the existing use of these drugs was gathered from the Prospective Urban Rural Epidemiological study. They assumed a 32% improvement in drug use from switching to a polypill, based on two earlier studies performed in LMICs. They also used current wholesale and retail polypill prices.
The following assumptions were made: patients either used or did not use a drug (missing doses was not modeled); each drug was equally effective whether taken as part of a combination or individually; and the frequency of serious adverse drug reactions (taken from published studies on individual drugs) would remain the same on the polypill. Such reactions would cause discontinuation of the polypill without switching to any of the individual drugs. Among controls, reactions to any drug would lead to stopping the pill concerned. Each patient who was taking one or more of the four drugs named above would instead receive a polypill. This would increase patient adherence and the duration of drug use as well.
The researchers factored in current medication use and major adverse cardiovascular events (MACE) over five years, namely, death due to CVD, heart attacks and strokes. They then introduced a single substitution for all evidence-based medications being used for cardiovascular disease, namely, the polypill.
The model then simulated the likely future course of the patients with respect to strokes, heart attacks, death, and healthcare costs. In addition, it provided estimates of survival odds, and of the QoL. Using all these parameters, the model came up with the incremental cost-effectiveness ratio, or ICER, which represents the expenditure required to prevent the loss of one disability-adjusted life year (DALY). This was assessed for cost-effectiveness in terms of the per capita GDP for each country per DALY prevented.
What did the study show?
The study showed that simply replacing every one of the four individual medications with the polypill could be the greatest breakthrough in secondary prevention of CVD ever known. Researcher Dhruv S. Kazi says, “In cardiovascular disease, we seldom identify interventions that have the potential to save a lot lives and, over the short term, also save money. LMICs that adopt the cardiovascular polypill for secondary prevention are likely to receive excellent clinical and health economic returns on investment - an important consideration when health care budgets are extremely tight.”
How did Kazi arrive at this conclusion? In main, it is due to the three most convincing results thrown up by the model. First, the polypill saves money that would otherwise be required to treat heart attacks and strokes occurring with the use of medications that comply with the standard of care in each of the countries included in the model. It is thus useful in saving money as well as lives.
The polypill could avert 40-54 MACE per 1000 treated patients over 5 years, but cause 3-10 adverse reactions/1000 over 5 years, mostly due to acute renal injury and hyperkalemia. The increased use of drugs and higher monitoring required, as well as increased survival, would cause increased healthcare costs, but these are compensated for by the cost savings on healthcare due to prevention of MACE.
The ICER was between 0.4% and 6% of the per capital GDP at wholesale prices, and between 3.3% and 14% at retail prices. The benefits are less striking (3-10% less DALYs over 10 years) when current usage rates are modeled. However, at a coverage of 50% or 75% of the eligible patients, 24% DALYs due to atherosclerosis could be averted. The polypill’s ICER is thus far better than that for other CVD interventions like community screening for CVD, individual drugs, and health education, and comparable to that of other public health interventions in widespread use like those for malaria, HIV, and HPV immunization.
Even at retail prices, it is as cost-effective as anti-retroviral therapy to prevent vertical transmission of AIDS in Africa. Earlier studies in developed countries support this finding.
The second finding deals with the dramatically increased likelihood that patients will get all required medications when the physician only needs to prescribe a single pill rather than four separate medications. This will dramatically increase the population covered by the potentially life-saving intervention, making all of these medications available to a wider population. This is the single factor that accounts for most of the benefit associated with polypill use.
For the first time, this study shows that single-pill formulations are hugely more beneficial in terms of ensuring standardized physician prescriptions rather than improved patient compliance, though the latter is also important since the patient only needs to take one pill rather than several.
The third result is the need to diagnose all eligible patients at the right time and put them on the polypill, to ensure that the full benefits of the pill are available to prevent recurrences of stroke and heart attacks. This is because of the very small percentage of patients in LMICs who are currently on at least one of the appropriate treatments for CVD.
Kazi sounds a note of caution: the polypill cannot replace all other efforts to reduce the incidence of CVD. He says, “n order to achieve meaningful improvements in health outcomes, LMICs adopting the polypill must also make strategic investments in high-quality health infrastructure and effective supply chains to ensure that patients with a prior history of heart disease or stroke have reliable access to an affordable cardiovascular polypill.”
In other words, making the polypill available will not ensure cost-effective coverage: rather, LMICs should scale up the infrastructure that will take the polypill to where it is needed.
The study was published in The Lancet, on August 30, 2019.
Cost-effectiveness of a fixed-dose combination pill for secondary prevention of cardiovascular disease in China, India, Mexico, Nigeria, and South Africa: a modelling study. John K Lin, Andrew E Moran, Kirsten Bibbins-Domingo, Bode Falase, Andrea Pedroza Tobias, Charuta N Mandke, & Dhruv S Kazi. The Lancet. August 30, 2019. DOI:https://doi.org/10.1016/S2214-109X(19)30339-0. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(19)30339-0/fulltext