A persistent public health problem

Cardiovascular diseases seem to lack the urgency that is ascribed to other illnesses, such as cancer – even as health conditions such as heart attacks and atherosclerotic heart diseases are killing millions of people every year. Rare have been the occasions when a public scare triggered decisive institutional action. The last time this happened was in 1955, when US President Dwight Eisenhower, who had smoked four packs of cigarettes a day, suffered his first heart attack. Eisenhower’s much publicized illness led to greater research funding. But since then – despite major medical improvements, a fall in mortality rates and concerted efforts from the World Health Organization (WHO), governments, academia, and private companies – cardiovascular diseases have remained a massive public healthcare burden. The reasons for this are manifold. While unhealthy lifestyles contribute to the bulk of heart-related deaths and hospitalizations, the complexity of the medical conditions and the sheer number of patients, as well as traditional low-risk attitudes toward heart diseases, compound the problem, which can only be solved if healthcare players work together. Importance of partnerships and prevention Heart disease, compared to other diseases, is often played down, experts say, because unlike cancer, which is considered a death sentence, cardiovascular disease is taken as a part of life. But nothing could be further from the truth. For example, patients suffering from heart failure die within five years of diagnosis. Life expectancy of other coronary diseases is similarly low if left untreated. And worse, some life-threatening heart conditions go almost unnoticed by patients, further reducing the urgency. But once patients are affected by a heart disease, their lives dramatically change, leaving many unable to continue their jobs or live independently. According to the Centers for Disease Control and Prevention, heart disease and stroke in the United States alone cost the healthcare system 216 billion US dollars per year, as well as an additional 147 billion US dollars in lost productivity. To solve this challenge, medical interventions per se are not enough, as the healthcare system itself is strained. Besides working on the development of novel therapies that can treat conditions from heart failure to atherosclerotic cardiovascular diseases, Novartis is also working together with institutional and private partners to tackle the systemic challenges in the healthcare sector. To increase awareness of the disease and work closely with healthcare system partners, the company, in the United States for example, is working together with hospitals, insurers and academic research centers. These include institutes such as the American Heart Association and the American College of Cardiology, among others. In other countries, where the healthcare system set-up is different, Novartis is collaborating with governmental institutions. In Japan, for example, the company is working with regional prefectures and academic institutes. This includes a collaboration with Japan’s Integrity Healthcare, a leading telemedicine company, which allows for efficient patient care, both remotely as well as at home. In Switzerland, meanwhile, the company is tying up with several healthcare insurers to broaden its reach.

Despite these efforts, the situation remains challenging since healthcare providers, including doctors, insurers and governments, are under increased stress given the large number of patients that need to be treated. “There is no one panacea that will solve everything, and everyone has to pull together to make a difference,” says Mei Haruya, who is building a cardiovascular disease partnership network for Novartis in Japan. “But we have to do everything we can to provide the best possible care for patients.” Steady clinical and medical improvement Although the situation is difficult, improvements have been substantial since the 1950s, when British epidemiologist Jeremy Morris found in a major study – in which he compared heart attack rates among double-decker bus drivers and conductors in London – that a lack of physical activity was a key factor for heart conditions. His work not only helped fan the popular fitness boom of the 1970s and 1980s.

His findings, which have led other researchers to conduct similar trials, still give credence today to the efforts of healthcare providers and governments to popularize physical activity and natural diets to maintain good health. “You can go back to ancient physicians and philosophers like Hippocrates and Siddhartha who said exercise is good for you,” Steven Blair, professor of exercise science at the University of South Carolina, told the New York Times when discussing the relevance of the work by Morris, who died in 2009, aged 99. “But they didn’t have any data. Jeremy was the guy who did the systematic research that invented the whole field of physical activity epidemiology.” Besides improved clinical understanding, medical innovation has been constant. Among the early movers in the field was Novartis predecessor company Sandoz, where researcher Arthur Stoll iso­lated the active principles of foxglove, a plant that had been used to treat heart conditions since the 18th century. Novartis predecessor company Ciba was also active in the field, focusing on Indian snakeroot. In 1953, researchers managed to isolate a new alkaloid from this traditional Ayurvedic plant, which was used to treat high blood pressure, among other indications. At about the same time, the pharmaceutical industry also started to develop more potent diuretics and anticoagulants, which help destroy plaques that accumulate in vessels and often lead to heart attacks. By the 1960s, when cardiac conditions were the number one killer in the industrialized world, calcium antagonists and beta-blockers reached the market, with Sandoz and Ciba among the key players. Innovation momentum remained high during the ensuing decades While cholesterol-lowering drugs were all the rage in the late 1980s and 1990s, Ciba-Geigy was successful with an ACE-inhibitor drug whose scientific advance would later give rise to an antihypertensive drug from Novartis. In 2007, Novartis launched a renin inhibitor and followed up with a heart failure medicine a decade later and is now sporting a broad portfolio of me­dicines that also includes treatments for bad cholesterol.

Continuing research and data-collecting efforts But even though there are more than 100 approved heart medicines on the market, more needs to be done in medical research, since one of the major obstacles in improving heart health is simplifying the treatment regimen, as well as developing longer-lasting medicines. Novartis is working on several research projects to this end, including a deeper dive into ath­erosclerosis with a special focus on therapies to reduce cholesterol and decrease inflammation. Strategies to reverse atherosclerosis are also explored. Furthermore, the company is working on compounds to treat specific forms of heart failure in which researchers are seeking to understand the mechanisms of certain conditions to develop novel therapies. But even as new therapies arrive on the market, healthcare practitioners are often reluctant to prescribe new medicines because they want to fully understand the medical implications of a new treatment since many of their patients suffer from other conditions too. “Cardiologists need much more data so that they can really be sure that prescribing a new treatment regimen is actually useful,” explains David Soergel, Head of Drug Development for Cardiovascular, Renal and Metabolic Diseases at Novartis. “This is not least because there are also implications for follow-up care due to the multimorbidity of many patients.” Traditionally, this requires pharmaceutical companies to run large clinical trials that often last up to a decade.

For one of its heart failure trials, Novartis included more than 8000 patients to test the drug’s efficacy as well as understand the side effects for specific patient groups. Such large clinical trials often present pharmaceutical companies with a Herculean task in terms of patient recruitment, as many patients do not know that they can participate. “There is no shortcut from the lab to a drug getting to patients and making an impact on public health,” Soergel explains. “It is upon us to increase awareness in that regard because the more awareness we create, the more people will want to participate in clinical trials.” Raising awareness From a medical point of view – although mortality rates have more than halved since cardiac-related deaths peaked in the 1960s – the high number of deaths seem intolerable, since most cardiovascular deaths are preventable, either by receiving the right treatment or cultivating a healthy lifestyle. According to the WHO, an estimated 18 million people died from cardiovascular diseases in 2019, representing 32 percent of all global deaths. Of these deaths, 85 percent were due to heart attack and stroke, most of them occurring in low- and middle-income countries. Out of the 17 million premature deaths under the age of 70 due to noncommunicable diseases in 2019, 38 percent were caused by heart diseases, most of which can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol.

Raising awareness of the need to adhere to a healthy lifestyle, therefore, remains a cornerstone of helping to improve public health and address the cardiovascular epidemic. Governments around the world, for example, have increased efforts to cut down on salt, cholesterol or trans-fat consumption, while health insurers are rewarding customers with discounts if they do sports more regularly. Novartis, meanwhile, also wants to improve adherence to existing drugs. “After a heart attack, which is one of the most life-changing experiences, almost all patients get started on high-intensity statins because it’s been shown to improve outcomes,” Soergel says. “A year later, less than half of the patients adhere to the therapy. Many people simply don’t like taking medicines. But the risk goes up exponentially.” The way out is to have longer-lasting medicines: “The next generation of treatments is already here – instead of having to take statins every day, you can have a shot at your doctor’s office, a sort of take-it-and-forget-it approach,” Soergel says. “This takes patient adherence out of the equation, and I think it will become much more appreciated over time.” The stakes are high. According to the WHO, some 500 million people stand at risk to develop a heart disease or diabetes over the next 10 years due to sedentary lifestyles, which could cost the world’s healthcare systems an additional 27 billion US dollars annually. Urging more physical activity, Tedros Ghebreyesus, WHO Director-General, said, “the benefits are huge, not only for the physical and mental health of individuals, but also for societies, environments and economies. We hope countries and partners will build more active, healthier and fairer societies for all.” While the situation still looks difficult, the odds that concerted efforts will lead to further improvements are intact: Ever since Jeremy Morris published his landmark study highlighting the need for physical activity and aerobic training, mortality rates have come down. While more than 500 out of 100 000 people in the United States died of a cardiovascular condition in the late 1950s, the number has since dropped to below 300. Although this figure is still too high, the declining trend shows that preventive measures and highly effective medicines can bring about lasting change.