Greater Use of Combination Therapy Would Reduce Heart Attacks and Strokes in Patients with Atherosclerotic Cardiovascular Disease, Yale Cardiologists Say

Reducing low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) leads to lower rates of heart attack and stroke, but fewer than a third of these patients typically reach the recommended goal of 70 mg/dL or lower. Kamil Faridi, MD, assistant professor of medicine (cardiovascular medicine) and Nihar Desai, MD, associate professor of medicine (cardiovascular medicine) at Yale School of Medicine, are calling for more universal use of combination lipid-lowering therapy, which they call a simple, safe, and effective approach that could improve ASCVD patients’ long-term health and save lives.

Existing guidelines recommend combination therapy based on a patient’s risk and level of LDL cholesterol. In theory, this involves physicians utilizing a stepwise approach including starting off patients on a statin [a common cholesterol-lowering drug], and if LDL cholesterol is not adequately lowered, prescribing a second agent down the line. But despite evidence supporting that these therapies are highly safe and effective, fewer than half of patients with ASCVD receive statins at adequate doses and fewer than 10% use an additional agent. By offering at least two lipid-lowering therapies up front regardless of LDL cholesterol level, physicians have the opportunity to prevent a significant number of heart attacks and strokes, Faridi and Desai argue in the American Journal of Preventive Cardiology.

“We know that over the past several decades, rates of atherosclerotic cardiovascular disease have been going down. But these rates have slowed, or even plateaued, in recent years,” says Faridi. “We’d like to see those rates of recurrent events continue to decline, and a key component of that would be to utilize effective guideline-directed medical therapy, including combination lipid-lowering therapy as we’re recommending.”

ASCVD is a clinical condition in which a patient with atherosclerosis suffers a cardiovascular event indicative of the disease, including symptomatic coronary artery disease, heart attack, stroke, or peripheral artery disease. Because cardiovascular diseases are the leading cause of death worldwide, using scientific evidence to guide patient treatment is incredibly important and can save lives, says Desai. Lifestyle changes like healthy diet and exercise are critical for disease management, he says, but secondary prevention measures including medications for managing blood pressure, diabetes, and cholesterol are also often necessary for reducing risk of future adverse events.

LDL cholesterol can build up in the arteries and induce an inflammatory reaction leading to arterial plaque. High levels of LDL cholesterol are associated with an increased risk of heart attack and stroke, especially in patients with ASCVD. Many large, randomized controlled trials have shown that lipid-lowering therapies reduce LDL cholesterol and in turn lower the risk of adverse events. Several lipid-lowering therapies are currently available, but most of the existing evidence supports statins, which are safe, well-tolerated, and cheap. Thus, the standard of care for all patients with ASCVD has been treatment with high-intensity statins. “They’re the mainstay of treatment for patients with atherosclerotic cardiovascular disease,” says Faridi.

However, in clinical practice, a substantial number of patients are not meeting the recommended LDL cholesterol guidelines. This may be due in part to what Desai describes as “clinical inertia.” In other words, physicians initially prescribe a medication like a statin but fail to make further therapeutic modifications even if the patients aren’t achieving their goals. “This suboptimal care results in higher rates of heart attack and stroke than we would like,” says Faridi. “We need a greater uptake of appropriate dosing of statins.”

Furthermore, over the past decade, newer medications for lowering LDL cholesterol have arrived on the market, including ezetimibe and PCSK9 inhibitors. When used in conjunction with statins, research has shown that these agents can reduce the risk of heart attack and stroke even further. “But they are massively underutilized in clinical practice, even though we know they’re very safe and effective,” says Faridi.

Faridi and Desai believe that offering two lipid-lowering medications off the bat will help more patients with ASCVD lower their LDL cholesterol to safer levels. Because the drugs are “incredibly safe” and typically well-tolerated, this protocol offers significant benefits with minimal risk, says Faridi. “It’s a simpler message,” he explains. “And we know we can do it safely with the medications available.”

The duo hopes to advocate for this approach both to cardiologists and to primary care providers who often manage patients with this disease. “A piece of advice I have for practitioners caring for patients with atherosclerotic cardiovascular disease is that even if they’re feeling fine, you can still impact their future and reduce their risk of events,” says Faridi. “I encourage practitioners to go ahead and prescribe a second lipid-lowering therapy agent for ASCVD patients in their care because we know in the long term it may improve not only their lifespan, but also their quality of life.”