Coronary artery disease cannot be resolved using existing technologies
In recent years, several therapeutic areas -- oncology (cancer) perhaps being the most notable -- have benefited significantly from the identification and development of biomarkers that yield clear insights into tissue function and the disease state at the molecular level. However, similar progress has yet to be made in cardiovascular disease.
Although cardiologists have a number of diagnostic tools – including blood analyses, exercise stress tests,
Personalised Therapy in CAD
electrocardiogram, X-rays, magnetic resonance imaging (MRI), and computerised tomography (CT) scans – at their disposal, these standard diagnostics do not provide an accurate assessment of risk of coronary plaque rupture or progression in an individual patient. Clinicians are therefore unable to individualise treatment – a situation that has led to a 20-year stagnation in biopharmaceutical investment in the treatment of atherosclerosis and coronary artery disease as a targeted indication.
CVD research has been limited by the inability to collect samples from the critical site of disease
Whilst the entire cardiovascular system is prone to development of atherosclerotic plaque, 75% of CVD deaths are caused by the rupture or erosion of plaque within the coronary arteries, a territory that represents less than 1% of the overall cardiovascular system. Given that the state of disease within the coronary arteries correlates to an individual’s risk of a heart attack or stroke, there is a great need for biomarkers that can reliably help clinicians predict patient risk as well as the extent of disease progression.
Inflammation proven to play a key role in CAD
The use of statin drugs to reduce lipid levels, particularly LDL cholesterol (LDLC), is a widely accepted strategy for reducing the incidence of CAD in people with high cholesterol and a high risk of myocardial infarction (MI, or heart attack), stroke or CVD death. However, despite the widespread use of statins, many people carry residual cardiovascular risk and as such suffer from serious cardiac events.
The inflammation hypothesis arose from observations that as many as half of all cardiac events occur in apparently healthy people with few “traditional” risk factors, including elevated lipids. Numerous studies have suggested that inflammation contributes to the destabilisation and rupture of atherosclerotic plaques, possibly leading to MI.
Several studies (CARE, AFCAPS/TexCPS, REVERSAL, PROVE-IT, ASCOT, A to Z, JUPITER) have shown the effectiveness of reducing levels of high-sensitivity C-reactive protein (hsCRP), a key marker of the inflammatory process. The IMPROVE-IT trial confirmed the efficacy of targeting both hsCRP and LDLC by successfully combining a statin (simvastatin) with an anti-inflammatory drug (ezetimibe). Most recently, the global cardiology community hailed the Novartis Phase 3 CANTOS study as a major breakthrough in validating the inflammation hypothesis. This randomized, double-blind study tested three doses of Novartis’ anti-inflammatory drug canakinumab against placebo in 10,061 patients with previous MI and an hsCRP level of 2mg or more per liter. Notably, a 150-mg dose of canakinumab was associated with a 37% reduction in hsCRP, no change in LDLC, and a statistically significant 30% reduction in revascularisations.
The CANTOS results are just the beginning to unravelling the potential of personalised medicine in patients with CAD, in that targeting inflammation in those with residual inflammatory risk appears to be a viable strategy for ensuring that the right patients receive the right therapy at the right time.