In Focus: Stories of progress

Cardiovascular Disease:

Innovating for longer and better lives

Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease, angina, heart attack, congenital heart disease and stroke. CVD was long considered an inevitable, though unfortunate, part of getting older. In the last 50 years, understanding of the interplay of various genetic, environmental and lifestyle factors have advanced considerably along with the available range of preventive medicines. While these medicines have had tremendous success saving and extending lives, CVD remains the leading cause of death worldwide today.

From understanding to managing risk

The field of study in CVD has made use of, and in many ways pioneered, long-term epidemiological studies. Observing participants in detail over a long period led to an understanding that a healthy diet, not being overweight or obese, not smoking, and regular exercise are all important in maintaining good heart health. One of the oldest and most successful cohort studies, the Framingham Heart Study, is the origin of the term ‘risk factor’.

With improved understanding of the risk factors for CVD, trials could be designed to determine whether these factors are causal. Lowering cholesterol with drugs, demonstrated its role in atherosclerosis and paved the way for lipid modification as a medical and public health prevention strategy.

In the 1970s, the first cholesterol-lowering agent was identified by a team lead by Akira Endo. It caught the attention of MSD who would go on to identify and market lovastatin in 1987. Synthetic statins were subsequently developed, including atorvastatin, at one point the world’s best-selling medication. Millions at risk of heart attack and stroke have benefited, with minimal management: one pill a day, with limited to no side effects. Statins remain the most widely prescribed class of medications today.

It was also found that anti-hypertensive drugs could reduce the risk of heart attack and stroke, confirming the pursuit of hypertension control as an effective health intervention.

Cardiovascular disease today: Improving access through partnerships and generic medicines

Investment in R&D for NCDs is crucial. Diseases such as hypertension no longer affect only developed countries, they are becoming more and more relevant in low income and middle-income countries.Mariângela Simão, WHO

Despite measurable progress, why does CVD remain the number one cause of death worldwide? In part, because people live longer. Controlling for age, the CVD death rate has declined in all high-income and some middle-income countries since 1990, although this decline has now stalled for many regions of the world. At the same time, incidence and mortality due to CVD has risen steadily in the developing world. Over three-quarters of CVD deaths take place in LMICs.

Improving access to generic medications, which typically cost significantly less than their brand-name counterparts, is one strategy available for addressing unmet health needs. With increasing availability and use, generic drugs account for almost 90% of all prescriptions in the US . Generic hypertensive and cholesterol medications saved the US health care system almost USD 60 billion in 2016.

Population-wide interventions such as reducing tobacco and alcohol consumption and promoting improved diets and regular exercise have been effective in many countries and can be implemented elsewhere.

Finally, joint programme and company-led access initiatives are helping to address access challenges.

  • AstraZeneca’s Healthy Heart Africa collaborates with non-governmental and community-based organizations, international organizations, health experts and governments to support local health systems by increasing awareness of the symptoms and risks of hypertension through education, screening, treatment and control. It aims to improve access to hypertension care and sells branded AstraZeneca medicines that are part of the program in a no-profit/no-loss business model. Since its launch in 2014 in Kenya, and 2016 in Ethiopia, it has conducted 5.7 million blood pressure screenings, trained over 5,000 healthcare workers, activated 675 healthcare facilitates and identified over one million people living with high blood pressure.
  • Pfizer collaborates with the international non-profit Population Services International to improve the diagnosis and treatment of hypertension, which impacts one-quarter of all adults in Myanmar and Vietnam as a leading cause of mortality. Its Healthy Communities program also provides hypertension management to underserved communities by aiming to screen more than 500,000 people and train up to 400 healthcare workers in 360 private sector health facilities.

Emerging solutions: From length of life to quality of life

The next big phase of genetics will be informatics, bringing together masses of data and trying to understand how hundreds of small genetic differences combine to put people at risk of a particular disease.Peter Weissberg, former Medical Director, British Heart Foundation

Although accounting for more than 30% of global deaths, CVD research has stalled. The R&D of new cardiovascular medicines represents less than 10% of global R&D spending. For one, a high regulatory bar demands ‘hard’ endpoints like reducing death and heart attack. It is also t hard to demonstrate a meaningful benefit over existing medicines.

Companies are looking to the successes in other areas of medicine, such as oncology, which has improved patient outcomes through precision medicine. Precision medicine allows doctors and researchers to predict more accurately which treatment and prevention strategies will work in which patients, considering their genes, environment and lifestyle. The first hypertension gene was discovered in 1998, and while the role of genes in CVD is not well understood, it is a very promising area of research. A precision medicine approach also means looking at biomarkers – the naturally occurring molecules, genes, or characteristics that signal particular diseases and specific pathological or physiological processes. Tracking these in a patient means that treatment can be adjusted according to their real-time development.

Yet, the number of people surviving a heart attack, or two or three heart attacks, has increased and there are many more people now living with very badly damaged hearts. Living with heart failure means the heart is weakened and cannot pump enough blood to meet the body’s needs. It remains a debilitating condition, often significantly reducing quality of life. But recent advances have shown that certain cells in the heart play a role in its repair and restoration, so-called progenitor cells.

CVD patients are also considered an at-risk population for developing serious complications from the flu, and studies have shown that influenza is associated with an increase of heart attacks and stroke.

Irregular heart beat (atrial fibrillation) is the most common cardiac arrhythmia. The majority of patients have non-valvular atrial fibrillation (NVAF) and the risk of stroke is five times higher in this patient population. For decades, the standard of care for NVAF required routine blood testing and frequent dose adjustments. Novel oral anticoagulants now offer potential advantages over previous treatments, including fewer drug interactions and fixed doses, without the need for routine blood testing.

Researchers are targeting inflammatory pathways to prevent cardiovascular events where there is a sudden drop in blood flow to the heart.

CVD research stands to benefit from sophisticated data-led advances that can bring to light insights from large-outcome trials that would otherwise remain hidden. Take, for example, the Novartis CANTOS trial which observed 10,000 patients over six years, showing that targeting inflammation in heart attack survivors reduces CVD risk. By linking population outcomes to specific genes, Amgen’s deCODE discovered a gene associated with a 34% lower risk of coronary artery disease.

The establishment of large, quality patient registries has fuelled large-scale real-world evidence generation, helping inform clinical debate as well as payer and regulatory decision-making. CVD-REAL is a recent example, a study of more than 700,000 patients with type-2 diabetes from registries spanning North America, Europe, Asia Pacific and the Middle East, looking at the use of diabetes drugs and their impact on critical cardiovascular outcomes. This research reflects a growing understanding of links between CVD and other conditions.

Finally, there is huge potential for digital technologies to revolutionise prevention and care. Companies collaborate with payers and other stakeholders to develop algorithms that can predict risk and drive early intervention. Big data, sensors and artificial intelligence open up the possibility of precise, real-time monitoring of patients – a whole new world for CVD.

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