Intended for healthcare professionals


Four in one polypill halves predicted cardiovascular risk, international study shows

BMJ 2011; 342 doi: (Published 27 May 2011) Cite this as: BMJ 2011;342:d3355

Does the polypill advance patient outcome in daily practice?

The luxury to practice effective prevention of cardiovascular disease
is partly based on the availability of several types of pharmacologic
treatments, including blood pressure lowering agents, statins and aspirin,
that reduce cardiovascular morbidity and mortality on population
level.(1;2) As a comprehensive risk reduction approach, the introduction
of the 'polypill' hence yielded high expectations,(3) in part due to lower
costs and better compliance. Although the benefits of individual
treatments have been established, the promised impact of the 'polypill'
remains uncertain.

Recently, the PILL collaborative group performed a good clinical
trial that puts down the potential benefits of introducing this treatment
to a large population that does not satisfy current criteria for
pharmacologic treatments.(4) However, it should be recognized that their
primary end-points are surrogate markers only. Subsequent estimations on
risk reductions hence are frail, as illustrated by a recent meta-analysis
that revealed cardiovascular benefits of aspirin in primary prevention
does not outweigh the increased hazards.(5) Moreover, balancing risk
reductions and side-effects is challenging. Consequently, a dilemma in
preventive treatment is anchored in targeting the appropriate patients.
The selection of high-risk patients favours the performance of the
intervention, but leaves out many low-risk patients.

In daily practice adherence appeared poor, i.e. only 60% after 5
years,(6) whilst risk reductions also depend on other modifiable factors
like smoking, lifestyle and diet.(1) The 'polypill' might induce a false
safety effect that may lead to discouragement and consequently a
contradictory hazardous effect of these non-pharmacologic factors. Before
rushing into introducing the 'polypill' and its side effects to large
populations, the net effect of this treatment should be more thoroughly
questioned. We wonder if the traditional patient-tailored treatment is
still the best alternative. In the hesitation on which trial to perform
next, we would encourage to conduct implementation studies with 'hard
cardiovascular endpoints' in order to provide useful and sustainable
results for daily practice.

Reference List

(1) Kesteloot H, Sans S, Kromhout D. Dynamics of cardiovascular and
all-cause mortality in Western and Eastern Europe between 1970 and 2000.
Eur Heart J 2006; 27(1):107-113.

(2) Wijns W, Kolh P, Danchin N, Di MC, Falk V, Folliguet T et al.
Guidelines on myocardial revascularization: The Task Force on Myocardial
Revascularization of the European Society of Cardiology (ESC) and the
European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J

(3) Yusuf S. Two decades of progress in preventing vascular disease.
Lancet 2002; 360(9326):2-3.

(4) PILL Collaborative Group. An International Randomised Placebo-
Controlled Trial of a Four-Component Combination Pill ("Polypill") in
People with Raised Cardiovascular Risk. PLoS ONE 2011; 6(5):e19857.

(5) Raju N, Sobieraj-Teague M, Hirsh J, O'Donnell M, Eikelboom J.
Effect of Aspirin on Mortality in the Prevention of Cardiovascular
Disease. Am J Med 2011.

(6) van Wijk BL, Shrank WH, Klungel OH, Schneeweiss S, Brookhart MA,
Avorn J. A cross-national study of the persistence of antihypertensive
medication use in the elderly. J Hypertens 2008; 26(1):145-153.

Competing interests: No competing interests

03 June 2011
Wouter D. van Dijk
PhD student, Family Medicine trainee
H. Luijks, M. van der Wel, C. Bakx
Radboud University Nijmegen Medical Centre, Department of Primary and Community Care