Elsevier

Therapies

Volume 74, Issue 2, April 2019, Pages 261-269
Therapies

Pharmacoepidemiology
Pharmacoepidemiology of statins

https://doi.org/10.1016/j.therap.2019.01.004Get rights and content

Summary

The evaluation of the real-life benefits and risks of statins in population is a major pharmacoepidemiological issue, given their widespread use for cardiovascular prevention. The purpose of this review was not to be exhaustive but to show the contributions of pharmacoepidemiology for various aspects of the evaluation of statins such as real-life drug use, effectiveness and risk. Statins are among the most used drugs in the world, but recent data show a slight decrease in use. Actual statin users are older, and have more comorbidities than those studied in clinical trials, but this does not seem to compromise their effectiveness, unlike the compliance issues that are common with these drugs. Beyond the known adverse reactions of statins from the clinical trials, risks of statins can be varied and sometimes difficult to evaluate, considering the ubiquity of cholesterol throughout the body, from drug or endogenous molecule metabolism to the construction of cell membranes or cell activities.

Section snippets

Abbreviations

    ACC/AHA

    American College of Cardiology/American Heart Assocation

    ACS

    acute coronary syndrome

    DUS

    drug utilisation studies

    EUROASPIRE IV

    European Action on Secondary and Primary Prevention by Intervention to Reduce Events

    HMG-CoA

    3-hydroxy-3-methylglutaryl coenzyme A

    ISPOR

    International Society for Pharmacoeconomics and Outcomes Research

    MINAP

    Myocardial Ischaemia National Audit Project

    REACH

    Reduction of Atherothrombosis for Continued Health (registry)

    SWEDEHEART

    Swedish Web-system for Enhancement and

Real-life drug use

Different perspectives can be distinguished for drug utilisation studies (DUS) of statins [15]. The general objectives of these studies are to measure, explain, predict or generalize what is observed but also to examine, analyse, or interpret these observations. Utilisation studies are the first descriptive step when looking at a drug.

Foremost, DUS allow to estimate prevalence (total number of users in a population during a given period) and incidence (new users in the population during a given

Effectiveness

Statins are one of the most studied drugs. Evidence from clinical trials is huge and several meta-analyses demonstrate the efficacy of statin in reducing mortality and cardiovascular events, mainly through lowering LDL-cholesterol, mainly during secondary prevention or in high cardiovascular risk patients [3], [4], [5], [63]. There is clear consensus on the benefit of statins in secondary cardiovascular prevention, although only simvastatin and pravastatin have demonstrated a reduction of

Risk

The contribution of pharmacoepidemiology to the evaluation of the risk of drugs, and especially its complementarity with pharmacovigilance, is well established [83]. Given the wide use of statins, their mechanisms of action by inhibiting cholesterol synthesis, a central element involved in the metabolism of many molecules, and the controversies surrounding these drugs, their risk assessment can be considered as somewhat unusual. Indeed, one might distinguish the known and quantified adverse

Conclusion

In the context of statin evaluation, pharmacoepidemiology has proven its usefulness to identify differences between target and joint populations and the impact of these differences on their effectiveness. Moreover, pharmacoepidemiology allows quantifying and studying the compliance of patients with this chronic treatment, whether for daily adherence or persistence over time, required to preserve the benefits of such treatment. Even if the real-world user population is older, and has more

Disclosure of interest

The authors declare that they have no competing interest.

References (123)

  • A. Saib et al.

    Evaluation of the impact of the recent controversy over statins in France: the EVANS study

    Arch Cardiovasc Dis

    (2013)
  • J. Bezin et al.

    Impact of a public media event on the use of statins in the French population

    Arch Cardiovasc Dis

    (2017)
  • P.K. Rannanheimo et al.

    Impact of statin adherence on cardiovascular morbidity and all-cause mortality in the primary prevention of cardiovascular disease: a population-based cohort study in Finland

    Value Health

    (2015)
  • L. Grimaldi-Bensouda et al.

    Real-life effectiveness of statins in the prevention of first acute coronary syndrome in France: a prospective observational study

    Int J Cardiol

    (2013)
  • J.L. Faillie et al.

    Pharmacoepidemiology and its input to pharmacovigilance

    Therapie

    (2016)
  • A. Gupta et al.

    Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase

    Lancet

    (2017)
  • C. Khouri et al.

    Muscle pain and statin, pharmacological or nocebo effect?

    Therapie

    (2018)
  • F. Lamoureux et al.

    Pharmacogenetics in cardiovascular diseases: state of the art and implementation-recommendations of the French National Network of Pharmacogenetics (RNPGx)

    Therapie

    (2017)
  • G. Corrao et al.

    Clinical significance of diabetes likely induced by statins: evidence from a large population-based cohort

    Diabetes Res Clin Pract

    (2017)
  • D. Adedinsewo et al.

    Prevalence and factors associated with statin use among a nationally representative sample of US adults: national health and nutrition examination survey, 2011-2012

    Clin Cardiol

    (2016)
  • Assurance maladie

    Usage des statines : une structure de consommation à améliorer, un potentiel d’économies majeur pour le système de soins - Point d’information

    (2013)
  • Cholesterol Treatment Trialists C et al.

    The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

    Lancet

    (2012)
  • F. Taylor et al.

    Statins for the primary prevention of cardiovascular disease

    Cochrane Database Syst Rev

    (2013)
  • Preventive Services Task Force U.S et al.

    Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement

    JAMA

    (2016)
  • A.L. Catapano et al.

    2016 ESC/EAS Guidelines for the Management of Dyslipidaemias

    Eur Heart J

    (2016)
  • J.J. Brugts et al.

    The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

    BMJ

    (2009)
  • M. Mitka

    Statin therapy in primary CVD prevention remains a hot-button topic for some

    JAMA

    (2011)
  • K.K. Ray et al.

    Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants

    Arch Intern Med

    (2010)
  • R.F. Redberg et al.

    Statins for primary prevention: the debate is intense, but the data are weak

    JAMA

    (2016)
  • J.H. Gurwitz et al.

    Statins for primary prevention in older adults: uncertainty and the need for more evidence

    JAMA

    (2016)
  • M. Elseviers et al.

    Drug utilization research: methods and applications

    (2016)
  • S. DeWilde et al.

    Evolution of statin prescribing 1994-2001: a case of agism but not of sexism?

    Heart

    (2003)
  • F.C. Taylor et al.

    Statin therapy for primary prevention of cardiovascular disease

    JAMA

    (2013)
  • T. Walley et al.

    Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997-2003

    Br J Clin Pharmacol

    (2005)
  • A.G. O’Keeffe et al.

    Time trends in the prescription of statins for the primary prevention of cardiovascular disease in the United Kingdom: a cohort study using The Health Improvement Network primary care data

    Clin Epidemiol

    (2016)
  • ANSM

    Analyse des ventes de médicaments en France en 2013. Rapport 2014

    (2014)
  • Assurance maladie

    Medic’AM. Données mensuelles et annuelles sur les médicaments remboursés par l’Assurance Maladie

    (2018)
  • K. Martin et al.

    Differences between clinical trials and postmarketing use

    Br J Clin Pharmacol

    (2004)
  • B. Ibanez et al.

    2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)

    Eur J Heart

    (2018)
  • S.C. Chung et al.

    Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries

    BMJ

    (2015)
  • K. Kotseva et al.

    EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries

    Eur J Prev Cardiol

    (2016)
  • D.J. Kumbhani et al.

    Adherence to secondary prevention medications and four-year outcomes in outpatients with atherosclerosis

    Am J Med

    (2013)
  • M. Sjölander et al.

    Few sex differences in the use of drugs for secondary prevention after stroke: a nationwide observational study

    Pharmacoepidemiol Drug Saf

    (2012)
  • A.J. Bagnall et al.

    Optimal medical therapy for non-ST-segment-elevation acute coronary syndromes: exploring why physicians do not prescribe evidence-based treatment and why patients discontinue medications after discharge

    Circ Cardiovasc Qual Outcomes

    (2010)
  • M. Pereira et al.

    Age and sex inequalities in the prescription of evidence-based pharmacological therapy following an acute coronary syndrome in Portugal: the EURHOBOP study

    Eur J Prev Cardiol

    (2014)
  • K. Homer et al.

    Statin prescribing for primary prevention of cardiovascular disease: a cross-sectional, observational study

    Br J Gen Pract

    (2015)
  • T.P. van Staa et al.

    The efficiency of cardiovascular risk assessment: do the right patients get statin treatment?

    Heart

    (2013)
  • J. Wu et al.

    Patient factors influencing the prescribing of lipid lowering drugs for primary prevention of cardiovascular disease in UK general practice: a national retrospective cohort study

    PLoS One

    (2013)
  • C.M. Gamboa et al.

    Race-sex differences in statin use and low-density lipoprotein cholesterol control among people with diabetes mellitus in the reasons for geographic and racial differences in stroke study

    J Am Heart Assoc

    (2017)
  • R. Fleetcroft et al.

    Variations in statin prescribing for primary cardiovascular disease prevention: cross-sectional analysis

    BMC Health Serv Res

    (2014)
  • View full text