Strengths and Limitations of Using the Polypill in Cardiovascular Prevention
Curr Cardiol Rep
Strengths and Limitations of Using the Polypill in Cardiovascular Prevention
Ambuj Roy 0
Nitish Naik 0
K. Srinath Reddy 0
0 Public Health Foundation of India, Delhi National Capital Region , Plot No. 47, Sector 44, Institutional Area, Gurugram 122002 , India
1 K. Srinath Reddy
Purpose of Review Polypill and its role in cardiovascular disease (CVD) prevention has been extensively discussed and debated since the inception of the concept in 2003. This article reviews the subsequent accumulated research in this area. Recent Findings Several short and intermediate to long-term studies with different brands of polypills have analysed the impact of polypill in phase II and III trials. The strengths of polypill that have emerged include better adherence, equivalent or better risk factor control and quality of life among polypill users as compared to usual care. The lurking limitations include difficulty with dose adjustment to targets, fear of mass medicalisation and low acceptability among physicians. Summary The current literature supports polypill use in reducing blood pressure and cholesterol levels for CVD prevention with improvement in adherence to medication. However, the long-term outcome of polypill on CVD events and mortality are unavailable and are currently being studied in clinical trials.
Polypill; Fixed dose combination; Cardiovascular diseases; Adherence; Secondary prevention; Primary prevention
-
President, Public Health Foundation of India, New Delhi, India
Introduction
The concept of polypill or a fixed drug combination (FDC)
was proposed, to reduce cardiovascular burden, rather
dramatically in a much cited paper by Wald and Law in the year 2003
[
1
]. They proposed that this polypill comprising of six drugs
(aspirin, statin, beta-blocker, angiotensin converting enzyme
(ACE) inhibitor, diuretic and folic acid) could reduce burden
of cardiovascular disease (CVD) by 80% when taken by all
above the age of 55 years and those with CVD. The concept
was based on research accumulated over years on the benefit
of blood pressure lowering, cholesterol lowering and
antiplatelet drugs in reducing CVD morbidity and mortality.
Over the last decade or so the story of the polypill has
progressed with both successes and disappointments [
2
].
This review discusses the potential role of polypharmacy,
the current state of research, strengths and limitations and
the future directions that we foresee for the polypill.
Importance of Polypharmacy in CVD Prevention
CVD is the leading cause of mortality worldwide [
3
]. This is
true of both the developed world and most of the developing
countries. While CVD burden is declining in the developed
countries, it is on the rise in developing countries with 80% of
the burden projected to be in the lower and middle income
countries (LMIC) by 2020 [
4
].
All current guidelines recommend aspirin and high dose
statins for patients with established cardiovascular disease
[
5, 6
]. In addition most patients with CVD are advised beta
blockers and ACE inhibitors as class I or IIA indication unless
specifically contraindicated [5]. Modelling and nested case
control studies have shown that this combination
pharmacotherapy leads to a 75% reduction in mortality in
patients with established CAD [
7
].
In patients without CVD, the strength of evidence for
polypharmacy is not well established. While the benefits of
management of individual risks like hypertension,
dyslipidemia are well documented general use of aspirin, and statins
remains controversial. Aspirin trials for primary prevention
reduce non-fatal MI but have little impact on mortality, while
consistently causing increase in risk of bleeding [
8
]. Similarly,
the utility/efficacy of statin for primary prevention is not well
established. Two large primary prevention trials did show
benefit of use of rosuvastatin in reducing cardiovascular outcomes
in individuals without CVD [
9, 10
]. However, they used a
biomarker or clinical risk identifier to include at risk
individuals to administer statin. Similarly, appropriate risk
stratification strategy to identify high risk individuals for primary
prevention with polypill needs to be tested before adopting it.
This could be based on clinical scores [10] or novel
investigations like calcium score, which has been claimed by authors
in a modelling paper, to substantially bring down the number
to treat (NNT) [
11
] as compared to basing it only on age as
proposed by Wald and Law.
Summary of Current Research
The last decade has witnessed development of multiple
polypills, with varying constituents, which have been tested
in different trials. The polypills considered here for CVD
prevention are those with at least one anti-hypertensive in
addition to aspirin and statin. A list of these polypills studied or
marketed is documented in Table 1.
These polypills have been studied in numerous research
trials in comparison to placebo or usual care. These (...truncated)