The use of anti-inflammatory canakinumab could reduce risk of heart attack

Results from a recent trial of the anti-inflammatory drug canakinumab have revealed it could help reduce risk of heart attack and mark the biggest breakthrough in cardiovascular treatment since statins.

The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) looked at people who previously suffered from a heart attack and tested whether administration of canakinumab  could reduce inflammation and reduce risk of future cardiovascular events (Ridker et al. 2017).

Speaking at the European Society of Cardiology Congress in Barcelona, where the findings were presented, Professor Paul Ridker of Harvard Medical School, said:

‘These findings represent the end game of more than two decades of research, stemming from a critical observation: half of heart attacks occur in people who do not have high cholesterol. For the first time, we’ve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk.’

According to Ridker this has far-reaching implications:

‘It tells us that by leveraging an entirely new way to treat patients—targeting inflammation—we may be able to significantly improve outcomes for certain very high-risk populations, he said.’

Outlining the trial

The trial was conducted by researchers from a wide range of international organisations, including the Center for Cardiovascular Disease Prevention and the Cardiovascular Division at Brigham and Women’s Hospital, Harvard Medical School, Boston; Novartis in East Hanover, NJ, and Basel, Switzerland; the Federal University of São Paulo; Universitätsmedizin Berlin; and the Academic Medical Center of the University of Amsterdam.

Participating centres in 39 countries enrolled patients who had a history of heart attack and an elevated blood level of high-sensitivity C-reactive protein. It is believed raised levels of this protein may lead to further heart attacks.

Participants received doses of 50 mg, 150 mg or 300 mg of either canakinumab or placebo. These were administered subcutaneously every 3 months. Patients were excluded from the study if they had any of the following:

• History of chronic or recurrent infection
• Previous cancer other than basal-cell skin carcinoma
• Suspected or known immunocompromised state
• History or high risk of tuberculosis or disease related to the human immunodeficiency virus
• Ongoing use of other systemic anti-inflammatory treatments.

The 10,016 participants recruited to the study were then monitored over the next 4 years. The researchers predominantly wanted to see whether participants suffered from additional heart attacks or stroke, or died from cardiovascular disease during this time.

In total, 1,490 participants experienced the main combined outcome of heart attack, stroke, or death from cardiovascular disease within the 4 years monitored. Within the placebo group, there was an average of 4.5 of these main events per year per 100 people. The treatment groups revealed there was no statistically significant difference between the 50 mg group, compared with placebo. The 150 mg group indicated a 15% lower risk compared with placebo (3.86 events per year per 100 people), while the 300 mg group showed a 14% lower risk (3.90 events per year per 100 people). The researchers concluded that 150 mg of canakinumab taken every 3 months led to a significant reduction in recurrent cardiovascular events compared with placebo.

Considering the results

The potential implications for medicine of this study are considerable, with mainstream media hailing it as a remarkable breakthrough (BBC 2017) and calling canakinumab a ‘new wonder drug’ (Donnelly 2017). For a drug traditionally used in the treatment of arthritis it certainly makes for great headlines. However, there are a number of considerations that must be taken into account before the drug is hailed as the medical advancement some have claimed.

Highlighting limitations

As mentioned, the study only looked at patients who have already had heart attacks. This is something many of the media’s headlines failed to convey (NHS Choices 2017). The effect of the drug, therefore, on reducing inflammation in people who have not had a heart attack, remains unknown. Additionally, many newspapers claimed that canakinumab was ‘better than statins’, but this is unhelpful as it does not reflect the nature of the study. It is thought that if canakinumab was licensed as a preventative medication, it is likely it would be given to people who wouldn’t benefit from taking statins (NHS Choices 2017).

Most importantly, before any changes can be made to the current licensing of the drug, further research is needed to confirm both the beneficial effects and the optimal dose. This was highlighted in an editorial by Dr Robert A Harrington of Stanford University published alongside the study (Harrington 2017), who called the clinical benefit of canakinumab ‘modest’. He argues that ‘a better understanding of the risks and benefits of this form of therapy is needed’ and raised concerns about the fatal infections encountered in the trial and sepsis. He also cites concern over the cost of using canakinumab in patients with a previous heart attack.

Cost matters

Canakinumab is currently licensed in the United States to treat systemic-onset juvenile rheumatoid arthritis at a cost of approximately $200,000 per year (Harrington 2017). While this pricing may be suitable for rare diseases, it is unsuitable for common indications such as coronary artery disease. Given the study was funded by Novartis, the manufacturer of the drug, substantial evidence of its benefit is needed before wider licensing of the drug can be considered.

References

BBC News. Anti-inflammatory drug ‘cuts heart attack risk’ [Internet]. London: BBC News; 2017 Aug 28 [cited 2017 Sep 7]. Available from http://www.bbc.co.uk/news/health-41071954

Donnelly L. New wonder drug hailed as biggest breakthrough in fight against heart attacks and cancer [Internet]. London: The Telegraph; 2017 Aug 27 [cited 2017 Sep 7]. Available from http://www.telegraph.co.uk/science/2017/08/27/new-wonder-drug-hailed-biggest-breakthrough-fight-against-heart/

Harrington RA. Targeting inflammation in coronary artery disease. N Eng J Med [Internet]. 2017 Aug 27 [cited 2017 Sep 6]. Available from http://www.nejm.org/doi/full/10.1056/NEJMe1709904

Ridker PM, Everett BM, Thuren T et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med [Internet]. 2017 Aug 27 [cited 2017 Sep 6]. Available from http://www.nejm.org/doi/full/10.1056/NEJMoa1707914?query=featured_home&#t=articleTop

NHS Choices. Anti-inflammatory drug may help prevent heart attacks [Internet]. 2017 Aug 30 [cited 2017 Sep 6]. Available from http://www.nhs.uk/news/2017/08August/Pages/Anti-inflammatory-drug-may-help-prevent-heart-attacks.aspx

Taken from British Journal of Cardiac Nursing, published December 2017.