Questionable benefit from polypill treatment.
The idea proposed by Wald and Law1
to treat all human beings above age 55 with a six-drug pill for the rest of
their life is fundamentally flawed. According to the authors this treatment
should reduce cardiovascular disease by more than 80% corresponding to 11-12
more years free of ischemic heart disease event or stroke.
Apparently, Wald and
Law have little clinical experience. They would else have known that many
unpredictable problems associated with multidrug treatment with all certainty
may reduce the alleged benefit.
Worse is that they have not included the risk of
dying in their calculations. This objection to their papers presented in “the
most important BMJ for 50 years” is most relevant because in many of the
studies included in their trial analyses total mortality was either unchanged or
higher after treatment. For instance, in a meta-analysis of the cholesterol
lowering trials performed before the appearance of the statin drugs, coronary
mortality was unchanged and total mortality increased by ten percent.2
In the three statin trials that included healthy people only, total mortality
was increased in one3 and unchanged in two,4,5 and in a
recent trial that included high-risk individuals only, the benefit from a
decreased cardiovascular mortality was neutralised by an increased mortality
Also, in most of the controlled, randomised trials
included in a meta-analysis of antihypertensive drug treatments,7
total mortality was not lowered significantly. This discrepancy between
cardiovascular and total mortality may be due to side effects of the treatments
or to the possibility that some of the deceased participants died from a
cardiovascular disease but had another diagnosis on their death certificate.
Whatever the cause may be, I am confident that few people are interested in
avoiding a heart attack by life-long polymedication if their risk of dying, in
particular from another disease, is unchanged or higher, considering the many
nasty alternative ways of dying.
NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80% BMJ 2003;326:1419-24.
U. Cholesterol lowering trials in coronary heart disease: frequency of
citation and outcome. BMJ 1992;305: 15-9.
RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, et al. Expanded
Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in
modifying plasma lipoproteins and adverse event profile in 8245 patients
with moderate hypercholesterolemia. Arch Intern Med 1991;151:43-9.
of Scotland Coronary Prevention Study (WOSCOPS) Group. Prevention of
coronary heart disease with pravastatin in men with hypercholesterolaemia. N
Engl J Med 1995;333:1301-7.
JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary
prevention of acute coronary events with lovastatin in men and women with
average cholesterol levels: results of the Air Force/Texas Coronary
Atherosclerosis Prevention Study (AFCAPS/TexCAPS). JAMA
Study of Pravastatin in the Elderly at Risk (PROSPER) study group.
Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a
randomised controlled trial. Lancet
LH, Agenäs I, Beerman B, Berglund G, Dahlgren H, Elmfeldt D et al. Måttligt förhöjt blodtryck. Report no.
121. The Swedish Council on Technology Assessment in Health Care, Stockholm
Competing interests: No competing interests