The adherence challenge in cardiovascular disease

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Cardiovascular diseases have a social and economic impact  

Cardiovascular disease is the leading cause of mortality globally, accounting for 17.9 million deaths a year,¹ with around  75-80% of these deaths taking place in low- and middle-income countries.² For example, in Russia, cardiovascular disease is the leading cause of death in men aged 49 or older.³ In addition, 37% of premature deaths (patients <70 years of age) are due to cardiovascular disease.¹ Between 2011 and 2015, it is estimated that the total cost associated with cardiovascular disease in low- and middle-income countries was $3.7 trillion; this translates to approximately half of the non-communicable disease burden and 2% of global GDP.² 

There are a variety of treatment options for cardiovascular disease, including both primary and secondary prevention methods; both ultimately have the goal to reduce complications. However, the efficacy of these treatments depends on the adherence to treatment regimen.

Key treatments in primary and secondary prevention of cardiovascular disease and recovery from cardiovascular disease 

Treatments for cardiovascular disease have evolved through the years, along with our understanding of how lifestyle factors can influence the disease progression or outcome. However, despite the availability of increasingly effective medications, there has not been a simultaneous and proportionate improvement in outcomes, since many patients don’t take their medications as prescribed. Since the 1950s, over 100 blood-pressure medications have been developed, with demonstrable benefits in cardiovascular disease. This is also seen in other drug classes, such as statins and anti-platelet therapies (Table 1). However, non-adherence can impede clinical improvements, and the lack of improvement in outcomes often leads to pressure to try alternative pharmacologic approaches, which may not have the intended effect in solving the challenge.

For cardiovascular disease, adherence varies by drug class and depends on whether the treatment is indicated for either primary or secondary intervention. The rate of global adherence to cardiovascular-disease medications is between 40-60%, meaning that roughly half of prescribed medications are not taken,⁸ with rates expected to be lower in developing countries.⁹ Even acute cardiac events do not necessarily improve adherence. In a study of more than 4 500 post-myocardial infarction patients, 18% did not once fill their cardiac-medication prescriptions in the 4 months after discharge from hospital (an example of non-fulfillment).¹⁰ In a separate cohort of more than 22,000 post-acute coronary syndrome patients, 60% discontinued their statin medication within 2 years of hospitalization (non-persistence).¹⁰ Thus, non-adherence to cardiovascular-disease treatments is significant. 

Non-adherence influences clinical and health-economic outcomes  

Low levels of medication adherence within cardiovascular diseases are often linked to poor control of cardiovascular risk factors, such as hypertension and hyperlipidemia and, in turn, this leads to worse clinical outcomes.¹⁰ A lack of adherence to therapeutic interventions can have a detrimental impact not only on the individual, but also a wider impact on the healthcare system and the economy.¹¹ This is represented disproportionately in low-to middle- income countries; in Sub-Saharan Africa, half of cardiovascular deaths occur in men aged 30-69, at least 10 years earlier compared to high-income countries.² The clinical burden of non-adherence is more clearly demonstrated in high-income countries such as the US, where there are 83.6 million cardiovascular-disease patients, 735,000 of them will experience a cardiac event, such as a myocardial infarction, with 210,000 going on to experience a recurrent event post recovery.¹² A study found that of patients hospitalized for myocardial infarction or with atherosclerotic disorders, those who were fully adherent (≤80%) to therapy (statins or ACE inhibitors) had a significantly lower rate of major adverse cardiovascular events than the non-adherent (<40%) group. ¹² An observational study by Roebuck et al highlighted increased adherence was associated with significantly fewer lower annual inpatient hospital days for dyslipidemia.¹³ 

This imposes a significant pressure on the healthcare system, whereby an estimated 200,000 premature deaths could be avoided in addition to the estimated costs to the European Union of EUR125 billion in excess healthcare services.⁸ This is a pattern seen globally, where the US has costs of $105 billion a year related to avoidable hospitalizations.⁸ As a secondary aspect to this, there are increased costs associated with outpatient care and emergency-room visits.⁸ Furthermore, 80% of cardiovascular disease-related patient deaths are in low- t0 middle-income countries, having a total economic loss due to cardiovascular disease of $3.7 trillion.²  These excess costs represent a significant economic burden in low- to middle-income countries, for example $20 billion in Brazil and $1 billion in Serbia, costs of cardiovascular care far exceed the health expenditure per capita.² This is only further emphasized by a lack of integrated healthcare, meaning disease is often detected at a late stage, contributing to a higher mortality rate within a lower age range.¹ 

Encouraging medication adherence, therefore, is crucial in chronic conditions such as cardiovascular disease. By encouraging adherence, optimizing patient–physician communication and aligning goals, there is a significant cost-benefit with a substantial long-term impact, including prevention of recurrent vascular events and a lower chance of hospitalization.⁸ 

References 
1. World Health Organization (WHO). Cardiovascular Diseases (CVDs) https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)  [Accessed 2 December 2020]. 
2. Gheorge et al. The economic burden of cardiovascular disease and hypertension in low- and middle-income countries: a systematic review. BMC public health 2018: 18-975 
3. GBD Russia Collaborators. The burden of disease in Russia from 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2018;392:1138-46 
4. Catarutti et al. Antihypertensive treatment in elderly frail patients: evidence from a large Italian database 2020 Hypertension; 76:00-00 
5. Khera R et al. Cost-related medication nonadherence in adults with atherosclerotic cardiovascular disease in the United States, 2013-2017. Circulation; 2019;140:00-00 
6. Bitton et al. The impact of medication adherence on coronary artery disease costs and outcomes: A systematic review Am J. Med 2013; 126: 357e.7- 357e.26 
7. Selak V et al. Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care. BMJ 2014;348:g3318 
8. Organisation for Economic Co-operation and Development, 2018. http://www.oecdlibrary.org/docserver/8178962c-en.pdf OECD Health Working Paper No 105: Investing in medication adherence improves health outcomes and health system efficiency: Adherence to medicines for diabetes, hypertension and hyperlipidaemia. 
9. Hamine S et al. Impact of mHealth Chronic Disease Management on Treatment Adherence and Patient Outcomes: A Systematic Review. J Med Internet Res 2015;17(2):e52 
10. Kronish, Ian M, and Siqin Ye. “Adherence to cardiovascular medications: lessons learned and future directions.” Progress in cardiovascular diseases vol. 55,6 (2013): 590-600. doi:10.1016/j.pcad.2013.02.001 
11. Cutler RL et al. Economic impact of medication non-adherence by disease groups: a systematic review. BMJ Open 2018;8:e016982.
12. Bansilal et al. Assessing the impact of medication adherence on long term cardiovascular outcomes. th J Am Cardio 2016 ;68 ;8 : 0735-1097
13. Roebuck C et al. Medication Adherence leads to lower health care use and costs despite increased health care spending. Health affairs 2011;30;1:91-99