Heart disease continues to be the leading cause of death and disability in the United States and worldwide. Atherosclerotic cardiovascular disease (ASCVD), caused by plaque buildup in artery walls, puts patients at risk of several life-threatening diseases and can be virtually overlooked until a major cardiovascular (CV) event occurs, such as a heart attack or stroke.
In the United States alone, more than 805,000 people are at risk of a heart attack, and for about 200,000 of them, this could be their second life-threatening heart attack event. More important, Almost 20% of people who have had a heart attack will be hospitalized again due to a second event within five years. These alarming statistics impact not only patients and their families, but also the workforce and the economy.
Cardiologists have made significant progress in preventing heart attacks or strokes due to high cholesterol. However, many patients remain at risk of ASCVD due to inadequate treatment, leaving them vulnerable to disease progression and potentially catastrophic events.
Statin therapy is the first-line treatment for the primary prevention of ASCVD in patients. Nevertheless, cholesterol control alone is not sufficient to prevent ASCVD-related diseases, as many statin-treated patients continue to suffer from acute cardiovascular events. Most physicians have remained focused on reducing patients’ risk of cardiovascular events through additional lipid-lowering therapies rather than addressing systemic inflammation as a factor contributing to ASCVD progression.
On average, each doubling of the statin dose results in a further reduction in LDL cholesterol (a major cause of ASCVD). However, this “Rule of 6” strategy can lead to, among other things, an increase in side effects. Even if increasing statin therapy normalizes LDL levels, the risk of a cardiovascular event still remains. Therefore, it is very important that doctors begin to recognize the effects of inflammation as a mostly untreated contributing factor to this disease.
For more than two decades, research has shown that inflammation plays an important role in the development of atherosclerosis and ASCVD. Since then, several clinical trials have shown that physicians can further reduce the risk of cardiovascular events in patients by targeting inflammation as a key therapeutic target for secondary prevention in high-risk patients.
Most important is a recent analysis published in The lancet found that residual inflammatory risk is a stronger determinant of recurrent cardiovascular events, cardiovascular death, and all-cause mortality than LDL-C.
Given this wealth of data demonstrating the importance of inflammation in cardiovascular disease, it is time for us cardiologists and physicians to additionally treat high-risk patients with anti-inflammatory therapies and aggressive lipid-lowering medications to further curb the progression of atherosclerosis.
The good news is that last year the US Food and Drug Administration (FDA) approved the first anti-inflammatory therapy option called LODOCO® (colchicine, 0.5 mg) to reduce the risk of a cardiac event in patients with established cardiac risk factors. The drug is safe and effective in addition to traditional statin therapy. Most importantly, it is cost-effective and can be easily made available to all patients with ASCVD who may not have had access to equivalent healthcare in the past.
Data supporting this approval included the LoDoCo2 trial, which showed that colchicine significantly reduced the risk of cardiovascular death, myocardial infarction, ischemic stroke, or ischemia-induced coronary revascularization by 31% compared to placebo. This represents an amazing effect that exceeds the reductions observed in current secondary prevention studies with additional lipid-lowering agents.
However, approved anti-inflammatory treatment is not enough.
For example, colchicine should not be prescribed to people with chronic kidney disease or liver dysfunction. These people represent a significant population that currently remains at risk of life-threatening cardiovascular events. Therefore, we need to continue to explore anti-inflammatory agents that can act synergistically with statins without affecting liver or kidney function to alleviate ASCVD.
In 2017, the CANTOS trial proved that anti-inflammatory action with canakinumab without lipid-lowering drugs can significantly reduce cardiovascular event rates by helping to establish the IL-1 to IL-6-CRP signaling pathway as a key target in cardiovascular disease define. Colchicine has also been shown to reduce multiple pro-inflammatory mechanisms by suppressing the NLRP3 inflammasome and inhibiting neutrophil migration into inflamed areas.
Several systematic reviews of anti-inflammatory medications have been conducted to examine their potential beneficial effects in patients with ASCVD. However, further research is needed to ensure that we provide the best possible care to patients with cardiovascular disease by also addressing the underlying systemic inflammation.
Although significant progress has been made in preventing heart attacks or strokes in patients, until recently not even doctors recognized the significant role that inflammation plays in the development of heart disease. Therefore, cardiologists and other physicians treating patients with ASCVD have continued to focus on additional aggressive lipid-lowering medications, with little success in further reducing the risk of a life-threatening cardiovascular event in their patients. However, it is paramount that we as physicians consider both cholesterol risk and inflammation to further successfully reduce the risk of a heart attack or stroke.
In the past year, we have made significant progress with an FDA-approved anti-inflammatory drug (LODOCO) that, when combined with lipid-lowering medications, can effectively treat heart disease. However, it is important that we continue to explore the potential beneficial effects of anti-inflammatory agents so that more patients can prevent life-threatening cardiac events.
Photo: BrianAJackson, Getty Images
Robert L. Quigley, MD, D.Phil., is an international health consultant and senior advisor for International SOS. He is co-founder and CEO of the International Corporate Health Leadership Council, a 501(c)(6) organization. Previously, he was Senior Vice President and Global Medical Director for Corporate Health Solutions at International SOS Assistance & MedAire in the Americas region, responsible for leading the delivery of high-quality medical assistance, healthcare management and medical transportation services. Before joining International SOS, Dr. Quigley was a triple-board certified cardiovascular and thoracic surgeon who directed two open heart programs at the Jefferson Health System in Philadelphia, where he served as a professor of surgery at Jefferson Medical College. He has a doctorate in immunology.