February 13, 2019

expert reaction to study looking at statins adherence and risk of death

Research published in JAMA Cardiology demonstrates that a low adherence to statin therapy was associated with a greater risk of dying.

Prof Stephen MacMahon, Principal Director, The George Institute for Global Health, said:

“This new report from the US shows that people with cardiovascular disease who stop taking statins are almost 50% more likely to die over a 2-3 year period.  Of course, there are many differences between those who stop treatment and those who don’t, and some of these differences such as older age, male gender and a complex medical history could well explain some of this increased risk (even after statistical adjustment).

“Nevertheless, the study serves to draw attention to the enormous problem of inadequate treatment for people at high risk of death from conditions such as heart attack and stroke.  The full complement of treatments for people with cardiovascular disease (including statins, aspirin and blood pressure lowering drugs, such as ACE inhibitors) will reduce the risk of further heart attacks, stroke and related deaths by around two-thirds.

“But still, as many as half of all those with cardiovascular disease do not receive all the treatments they need.  In part this is the consequence of patients stopping treatment, even although side-effects are uncommon.  But in part, it is also the consequence of doctors not prescribing all the relevant treatments, despite clinical guidelines emphasising their importance.

“We urgently need solutions for both these problems if we are to realise the full potential of statins and other life-saving drugs.  Solutions involving digital technologies, such as those recommended by the recent Topol Report, almost certainly offer the greatest promise.”

Prof Kausik Ray, Professor of Public Heath, Imperial College London, said:

“Statins are proven therapies to reduce the risk of heart attacks and strokes in those with and without established vascular disease such as prior heart attacks, bypass, or strokes.  As these treatments are required to be taken daily, for life, long-term adherence is essential to achieve sustained reductions in bad cholesterol (LDL-C) and thus reduce the long-term risk of heart disease and strokes.

“This is a large study using electronic health records in over a third of a million patients with prior vascular disease in the USA.  They show a graded relationship between the most adherent to the least adherent – least adherence had a 30% increased risk of dying from any cause vs the most adherent.  The study found that specific groups women, minority groups, and those at the extremes of age (young and old) were less likely to be adherent to medications.  Greater focus is needed around health literacy and patients understanding the need for adherence and its benefits for long-term outcomes during patient doctor consultations.

“Of note this study confirms and supports the findings from our own large study in JAMA Network Open (Khunti K, Ray KK Nov 2018) in a comparable UK population where we linked the combination of adherence and statin dosing to reductions in cholesterol and also outcomes.  This large real world observational study again demonstrates that those at high risk of cardiovascular disease benefit from statins.  A greater focus should now be placed on adherence and reassuring the public about the benefits.”

Prof Peter Sever, Professor of Clinical Pharmacology & Therapeutics, Imperial College London, said:

“One of the largest and most impressive observational studies on statin use in over one third of a million patients.  The data provide powerful evidence that poor compliance with statins is associated with an increase (30%) in cardiovascular death.  Combined with other studies showing that stopping statins or reducing the effective dose of statin, puts patients at a substantial increase in cardiovascular risk, this report provides robust evidence to counter unfounded claims that statins cause more harm than benefit.”

Prof David Webb FRSE FMedSci, Centre for Cardiovascular Science, The University of Edinburgh, and Past President, British Pharmacological Society, said:

“This large retrospective cohort study builds on a large body of work showing that good adherence to medicines, such as for heart failure, high blood pressure and atherosclerotic vascular disease, is associated with better outcomes for patients.

“The benefits of statin adherence in this study are likely to be two-fold: (1) linked to the direct benefits of statin in reducing vascular disease, and (2) associated with the behavioural differences between individuals who are strongly adherent to treatment and those who are not.  Importantly, people with good adherence to treatment tend to have healthier lifestyles, such as better diet, more physical activity and less smoking, and have better support systems.  This study, in patients within the US Veteran Affairs Health System, also confirmed previous findings that women and minorities are less likely to show good adherence.

“If the differences in outcome could be largely attributed to broader behaviours, then improving adherence might have modest benefits.  However, the authors used a range of techniques – including benefits with high vs. low intensity statins and adherence to other cardiac medicines – to indicate that the direct effect of statins is important, and adherence remains an important target.  Although better approaches to adherence are being developed (such as smartphone reminders and psychological support), poor adherence to medicines remains an important reason for poor outcomes in many chronic conditions.”

Dr Amitava Banerjee, Associate Professor in Clinical Data Science and Honorary Consultant Cardiologist, UCL, said:

“There are two aspects to taking medications: ‘adherence’ (taking the drug as prescribed) and ‘persistence’ (continuing to take the drug over a particular time period).

“This large, representative study from the USA looked at whether adherence to statins affected mortality in stable patients with a diagnosis of cardiovascular disease (most commonly coronary artery disease and stroke).  Previous studies have considered short-term adherence and have not looked across all subgroups and all levels of adherence.  Although this was an observational study rather than a trial, the authors controlled for the majority of confounding factors.  There were two key findings.

“First, the higher the adherence to statins, the lower the mortality.  In other words, the more you stick to taking your statin, the more likely you are to see benefit.  The “healthy adherer effect” (where people who are more adherent to drug therapies tend to have healthier lifestyle behaviours) was accounted for by the authors, and so adherence to the statins is driving this benefit.

“Second, there were certain groups (women and ethnic minorities) who had lower adherence, which has been shown previously.  The reasons for this poor adherence need to be elucidated, as we are currently lacking effective interventions to improve adherence.

“In summary, drugs do not work if you do not take them.  If statins are recommended and prescribed by your doctor, then we need to focus much more on adherence.”

‘Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease’ by Fatima Rodriguez et al. was published in JAMA Cardiology at 16:00 UK time on Wednesday 13 February 2019.

Declared interests

Prof Kausik Ray: “I have consulted for companies developing therapies for cholesterol management, diabetes and anti-platelet therapies to prevent cardiovascular disease.”

Prof Peter Sever: “I’ve received grant funding, honoraria and consultancies from Pfizer and Amgen.”

Prof David Webb: “I have no relevant conflicts.”

Dr Amitava Banerjee: “Advisory boards with Boehringer-Ingelheim, Novo-Nordisk, Pfizer and Astra-Zeneca.  Trustee of the South Asian Health Foundation.”

None others received.