In the United States, cardiovascular disease accounts for over 800,000 deaths per year (approximately 1 death every 40 seconds). In addition, around 92 million adults live with some form of cardiovascular disease or complication due to stroke. The cost both in terms of health expenses [expenditures] and lost productivity is estimated at over $316 billion. Globally, cardiovascular disease is the leading cause of death with over 17 million deaths per year; split almost equally between stroke and coronary heart disease. Thus, this disease takes a hefty toll on society. In recent years, several scientific advances and new insights into disease pathology have come to light, and may pave the way for better treatments to reduce both death and/or disability associated with cardiovascular disease. A few of the most exciting scientific breakthroughs are highlighted below in recognition of World Heart Day, which is today, September 29.
Availability of Valve Replacement Options in the Elderly and Intermediate-risk Patients
Better options may be available for patients with aortic valve stenosis, a narrowing of the opening in the heart valve. Aortic valve stenosis leads to restriction of blood flow from the hearts lower chamber to the main artery in the body – the aorta, causing chest pain, fatigue, shortness of breath, and more seriously, heart failure. Treatment usually involves open-heart surgery which is not an option for patients at high surgical risk or in patients with inoperable severe aortic stenosis. For high risk patients where surgery is not possible, transcatheter aortic valve replacement (TAVR) is typically used. TAVR requires only a small opening whereby a catheter is placed in the femoral artery (or through an artery in the chest), guided into the heart chambers, and once correctly positioned a heart valve device is deployed. Thus, this surgical procedure is much less invasive. TAVR has been approved for high-risk patients since 2011 but results from 2 recent clinical trials (PARTNER 2 and SURTAVI) have paved the way for approval by the Food and Drug Administration for an expanded indication of valve replacement devices (Corevalve Evolut R System, Sapien 3 and Sapien XT) in intermediate-risk patients, making this technology more accessible to a larger patient population.
Reduction of Stubborn Cholesterol Levels
There is new hope for patients with consistently elevated levels of the harmful cholesterol, low-density lipoprotein cholesterol (LDL-C). Monoclonal antibodies called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to be very effective in lowering stubborn LDL-C. Alirocumab (Praluent) and evolocumab (Repatha) work by acting on liver enzymes to pull harmful cholesterol from the circulating bloodstream. Results from a newly completed clinical trial (FOURIER), enrolling over 27,000 patients with cardiovascular disease, showed that evolocumab reduced LDL-C by 59% and more importantly, patients had a lower risk of non-fatal heart attacks and non-fatal stroke. Alirocumab, another PCSK9 inhibitor also reduced bad cholesterol by 58% in over 2,000 patients (ODYSSEY clinical trials) and lowered the risk of cardiovascular events. Alirocumab is currently being tested in a larger clinical trial with around 18,000 patients; this new trial is designed to evaluate whether alirocumab reduces coronary heart disease, major non-fatal coronary events (heart attacks, hospitalization for chest pain due to the heart muscle not getting enough oxygen [angina]), or ischemic stroke. Both evolocumab and alirocumab are designed to be used as a supplement to (not instead of) other treatments.
Another PCSK9 inhibitor, inclisiran, may also be available soon. Inclisiran is different from the 2 drugs listed above as it uses a small interfering RNA to target PCSK9 messenger RNA. A newly completed, phase 2 trial (ORIAN-1) showed a 27% to 52% reduction in LDL-C in patients at high cardiovascular risk over an 8 month period (240 days). Thus, patients struggling to control their cholesterol levels have several new drugs to help augment their current therapies.
Diabetes Drugs are Working Overtime
Type 2 diabetes is a risk factor for cardiovascular disease and the combination of both type 2 diabetes and cardiovascular disease increases a patient’s risk of death. Several drugs are now available that work double-duty to both lower glucose and reduce the risk of cardiovascular events. The glucose lowering drugs, liraglutide and empagliflozin, reduced the risk of cardiovascular death and hospitalization for heart failure in their respective clinical trials (LEADER and EMPA REG OUTCOME, respectively). In the LEADER clinical trial, over 9,000 patients were randomized to receive study drug or placebo. Patients administered liragutide had a lower risk of cardiovascular death, non-fatal heart attacks, or non-fatal strokes, and fewer hospitalizations for heart failure were reported. In the EMPA REG OUTCOME trial, over 7,000 patients were enrolled to receive empagliflozin or placebo. Empagliflozin reduced the rate of death from cardiovascular causes, and also reduced hospitalization for heart failure. As an added benefit, empagliflozin also reduced body weight and blood pressure.
Developing a Heart Through 3-D Printing Technology
As we look into the future, we may see heart transplants using artificial hearts developed through 3-D printing technology. Researchers at the Functional Materials Engineering at ETH, Zurich, have created a heart with soft, flexible materials. The artificial heart is about the same size as a human heart, is made from silicon, consists of one single part (monoblock), and has a left and right ventricle. This design means that it would only need to be fitted where the input and output ports are located for moving blood in and out of the heart. The research reported that the artificial heart fundamentally works – it mimics blood flow and pressures similar to a human heart. However, this technology is still in its infancy. The current prototype only lasts for about 3,000 heart beats, and functionality in practice will likely vary depending on a patients’ heartbeat. Thus, it will be a while before we see real world application of this technology, but it would be an ideal bridge for patients waiting for a transplant.
New medicinal products, procedures, and technologies in the cardiovascular health space give us plenty to be excited about as we observe World Heart Day 2017.