statin

Introduction

On February 27 1998, the members of the Danish parliamentarian health committee

received a letter from three leading cardiologists, Ole Færgeman, Torben Haghfelt

and Torsten Toftega˚rd Nielsen, advocating for a more open approach to the

reimbursement rules for cholesterol lowering drugs in Denmark. The use of statins

in Denmark had for some time lagged behind the uptake of statins in other

Scandinavian countries. In the letter, it was stated that in Denmark: ‘‘346 patients

die each year due to lack of this treatment, the same as one patient per day.’’

(Færgeman et al. 1998, p. 35751

). The numbers were extracted from the then freshly

published Scandinavian Simvastatin Survival Study (4S) in which the correlation

between decreased mortality and statin use was established for the first time among

patients with manifested coronary heart disease (Scandinavian Simvastatin Survival

Study Group 1994). Færgeman and Haghfelt functioned as the Danish 4S project

leaders and had for more than 30 years advocated for an increased focus on

cholesterol lowering interventions as a way to strengthen the health of the Danish

population. Still, the Danish state authorities together with several independent

medical practitioners continued to be cautious in their approach to this new

treatment regimen. When they delivered the letter to the health committee, the

majority of physicians were already convinced of the benefits of cholesterol

reduction. However, they needed the political approval and technological interventions necessary to actually implement pharmaceutical cholesterol reduction in

practice.

In this article, we use the notion of ‘routinization’ as a way to conceptualize the

process whereby new contested technology transforms from experimental to

standard of care.

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Since 1933, the Danish welfare state has provided free universal health care to all

its citizens, which means that no fees are paid when you go to your general

practitioner or when you are hospitalized

. Likewise, the costs of medicine are partly

state funded meaning that prescription medicines are fully reimbursed once one’s

own contributions towards meeting the costs have exceeded approximately 500 US

dollars, while costs between 200 and 500 US dollars are partly covered.

This system

also implies that the state health authorities have a very powerful command over the

use of medicines in Denmark given that they regulate which medicines are approved

for reimbursement and under what conditions. This stands in contrast to the

American health infrastructure, where, although the federal Food and Drug

Administration (FDA) obviously has a major regulatory role to play, the costs and

reimbursements of medicine expenditure are usually the concern of private health

schemes, insurance companies or the patients themselves. These differences in

health infrastructures have a huge bearing on what Kaufman has dubbed ‘‘the chain

of drivers’’ behind ordinary medicine (Kaufman 2015) since a number of key

drivers are actually not the same.

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While we are well aware of the larger systemic or

organizational drivers behind the routinization of statins at the global level, the

pharmaceutical regime did not implement itself. Rather, the transformation of

knowledge into practice was brought about by a group of individuals, whom we

name the ‘therapeutic reformers’ (Marks 1997). In Marks’ understanding of the

term, the therapeutic reformers constitute a political community;

a group joined by their belief in the power of science to unite both medical

researchers and practitioners despite obvious differences of training and

circumstances. Although connected in some cases by the accidents of personal

biography, what binds reformers is the shared belief that better knowledge

about the effects and uses of drugs will lead directly to better therapeutic

practice (p. 3).

This article is a part of the interdisciplinary LIFESTAT project (‘‘Living with

Statins’’), which leverages approaches and knowledge from health sciences, the

humanities and social sciences to analyse the impact of statin use on health, lifestyle

and wellbeing among Danish citizens (Christensen et al. 2016).

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y LIFESTAT project (‘‘Living with

Statins’’)

. More research is published on the benefits of statins. The pharmaceutical industry is now the most profitable business in several countries. The

voice of the antagonists of cholesterol management is attenuated

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. However, along the way this

epistemological doubt transformed into a perception of the inevitable necessity of

preventive medicine.

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By recognizing the

limitations of medical knowledge and the uncertainties inherent in pharmaceutical

risk reduction, from very early on, Færgeman subscribed to a view of health policy

decision making that corresponds very well with later notions of evidence-based

medicine (EBM), namely basing medical decision making on scientific evidence

rather than relying on personal experience and beliefs (Sackett et al. 1996)

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Cholesterol Campaign of 1988

By the late 1980s, a series of initiatives were established among which the

Cholesterol Campaign of 1988 was one of the largest. The campaign which was

The Rise of Statins in Denmark: Making the Case…

organized by the DHF in partnership with several media agencies, numerous general

practitioners as well as politicians, helped disseminate to the wider public

information on the importance of cholesterol management in clinical practice and

everyday life. Not surprisingly, the campaign was headed by a handful of

protagonists that included John Godtfredsen, Torben Haghfelt and Ole Færgeman.

Like Færgeman, Godtfredsen and Haghfelt were leading scientists within the field of

CVD, working at the intersection of clinical practice and research, and with a foot

each in both the Danish Society of Cardiology and the DHF. As such they trespassed

on the boundaries of ‘pure’ research and stepped into what Jasanoff has described as

a hybrid science-policy field (Jasanoff 1987).

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. Through the processes of making high

cholesterol a public health problem, the scientific elements of the cholesterol dispute

were transformed. From a situation where the dispute was seen as belonging to the

realms of laboratories and epidemiological trials, the controversy moved into a

realm of public policy where an awareness of the problem was co-produced with its

possible solution (Jasanoff 1995). Following on from the 1986 clarifying report and

the consensus conference in 1986, Færgeman and colleagues had used the public

activities of the DHF to simultaneously further the cause of cholesterol research and

management, which blurred the fine line between public and scientific interests. For

instance, during a festival in the second largest city of Denmark, A˚ rhus, the DHF (in

collaboration with the local municipality and research committee) invited all

citizens of the municipality to participate in health screenings at the city hall. For

the first time ever, this enabled the scientists to test a risk model for opportunistic

screening of risk of CVD in Denmark (Gerdes and Færgeman 1988). From a

protagonist’s perspective, this initiative could be seen as an exemplary academic

outreach activity in the interest of public health, but in the eyes of the antagonists it

amounted to a suspicious popular staging of twisted evidence.

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‘‘The Scandinavian

Simvastatin Survival Study (4S)’’ initiated in 1988. Sponsored by Merck, Sharpe &

Dohme (MSD), the study aimed at proving that statin treatment of patients with

coronary heart disease decreased mortality.

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The Danish primary investigators, Ole

Færgeman and Torben Haghfelt, presented the first results of 4S in an article in The

Danish Medical Journal in 1995. The main endpoint of the study was death, and the

trial showed an impressive 30% reduction in mortality in the statin treated group

compared to the placebo group. Based on these results, Færgeman and Haghfelt

estimated that statin treatment could not only save the lives of thousands of Danes,

but also reduce the health care costs by billions (Færgeman and Haghfelt 1995).

These results continue to appear in the newest clinical practice guidelines on the

prevention of CVD as one of the main arguments behind the logic of risk reduction

The Rise of Statins in Denmark: Making the Case…

in clinical practice, hence had a pivotal influence on the closure of the cholesterol

controversy in Denmark.

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In 1999, the Danish government launched the Public Health Programme (1999-

2008) which focused explicitly on prevention. In his capacity as spokesman for the

Danish College of General Practitioners, Hans Kallerup published a note in the

Danish Medical Journal, on the status of ‘‘The General Practitioner as ‘preventer’’’.

In the note he argued that ‘‘The year 1999 created the basis for the general

practitioner as a central figure in the healthcare system in the next millennium’’

(Kallerup 2000, p. 1709). The new public health programme favoured the role of the

GPs and actively built them into the programme as the crucial actors in the attempt

to increase the lifespan of the Danish population especially through the logics of

prevention (Sundhedsstyrelsen 1999).

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The tool was invented as part of a doctoral project undertaken by MD Troels

Frølund Thomsen. In a recent interview, Thomsen elaborates on the origin of the

idea:

During a ward round [as part of an internship at Glostrup hospital, Denmark

1990], I came to see a male engineer suffering from a minor infarct. I clearly

remember how I entered his ward, with the wife talking to the nurse next to the

bed. It was December and there was snow outside and candlelight inside, you

know, one of these really cosy winter days. The patient had elevated blood

pressure, nothing great just a little bit, and he smoked 10 cigarettes per day. So

he asked me; ‘‘Doctor, what should I do? Quit smoking or start taking blood

pressure medication?’’ He wanted only one answer; one solution to his

problems. I told him to quit smoking, but I guess I was biased since I had been

a part of the militant non-smokers frontier as a young person, and because I

never really liked smoking. And then the patient said; ‘‘Well, now it is four

The Rise of Statins in Denmark: Making the Case…

against three. Four of your colleagues advise me to quit smoking, and three

advocate for the pill. What do you now think I should do?’’ To me this was

really an eye-opener, because it clearly displayed our lack of insight into the

risk of individual patients. I took the case to my supervisor, and in the next

conference he asked if I could figure out how to give the same answer to all

our patients, which became the starting point for the development of the risk

assessment tool.

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. Originally named PRECARD (PREvention of CARdiovascular Disease), the

tool became the solution that would guide this quest (see also Bauer 2008). The

programme was based on knowledge derived from epidemiological trials, originally

the ‘‘Glostrup Population Studies and the Copenhagen Heart Study’’ (Thomsen et al.

2001). It was introduced for the first time in 1999, and 3 years later it was installed

in one-third of all practices in Denmark (Bauer 2008). Later, in 2003, it was adopted

by the European Society of Cardiology and recommended as the European CVD

prediction and management system by the Third Joint task force on CVD Prevention

(De Backer et al. 2003) and expanded to 43 countries in- and outside of Europe

under the new name: HeartScore (Bonnevie et al. 2005). The programme filled a gap

in the practical management of CVD prevention in clinical practice by transforming

large amounts of data into simple facts that could be easily visualized. Furthermore,

the programme transcended EBM as it functioned not only as a way to access the

risk of individual patients but also served educational purposes by supporting the

general practitioners attempt to promote healthy living (Bauer 2008)

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‘‘one person dies every day due to lack of

S. R. Lau et al.

statin treatment, […]

By the late 1990s, the dispute over the cholesterol hypothesis almost completely

vanished from the pages of the Danish Medical Journal. With the release of the 4S

study results, which were supported by other statin trials released during the second

half of the 1990s (Greene 2007; Steinberg 2007), the battle between protagonists

and antagonists of cholesterol management had been settled. Although antagonists

continue to challenge the raison d’eˆtre of cholesterol management in websites and

popular media, the decade long controversy over cholesterol in the community of

general practitioners was replaced by a general agreement that lowering cholesterol

was an important rather self-evident part of CVD prevention.

. While the safety of prescribing

statins for heart healthy individuals is still heavily debated in scientific milieus

(Godlee 2014; Kristensen et al. 2015), in healthcare practice pharmaceutical

management of high cholesterol has become standard of care (Greene 2007; Dumit

2012; Christensen et al. 2016).

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. Finally, the prescription of

statins as a supplement to health promotion was authorized through the liberalization of reimbursement rules. During the course of routinizing high cholesterol

management, the epistemological doubt in the new treatment regime was

transformed into a view of pharmaceutical prevention as an inevitable and

necessary part of high quality healthcare. Despite ongoing scholarly disagreement

about the effectiveness of prescribing statins for heart healthy individuals

(Abramson et al. 2013; Godlee 2016; THINCS 2014), in medical practice the

contested evidence has been transformed into standard of care.

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