Clinical trial may help lower inherited risk of heart attack

On a Saturday morning, two days after his 50th birthday, Richard Tran went cycling with his friends, a group he regularly rides 20-60 miles with on weekends in the summer.

When they took a break — about 40 minutes into the ride that day — Tran noticed something was wrong.

“My chest started to hurt and it just kept getting worse — nothing I did seemed to help,” he says. “Then my left arm went numb. That’s when I wondered if I was having a heart attack.”

Tran was taken by ambulance to a local hospital, where he learned his suspicions were correct — a blockage in one of his arteries had obstructed blood flow to his heart. His care team was able to clear the blockage and insert a stent (small tube) to keep the artery open.

Tran made a full recovery, but he was left with an unsettling question: Why had his heart attack happened in the first place?

“I was 50 years old, in pretty good health, with no other issues going on,” he says. “It didn’t make sense.”

The hunt for an answer

Three months after his heart attack, Tran embarked on a quest to uncover what caused it. His doctor checked his blood pressure and ordered a lipid panel — a blood test that measures fat molecules called lipids, which can increase a person’s risk of cardiovascular disease.

However, neither of those screenings yielded results that would explain his heart attack, so Tran began doing some research.

“Online, I found some instances of young people, in their 40s and 50s, having heart attacks, and most of them had one thing in common — high Lp(a) levels,” he says. “I had never heard of Lp(a).”

Tran isn’t alone. While many are familiar with the role that high levels of cholesterol and triglycerides play in cardiac events, Lipoprotein(a) — also known as Lp(a) — and its risks are less known outside the medical community.

Elevated levels of Lp(a) — a sticky molecule that carries fats through your bloodstream — can increase the risk of heart attack and cardiovascular diseases, such as arteriosclerosis and aortic valve stenosis.

“The amount of Lp(a) is genetically determined for about 70 to 90 percent of people,” says Dr. Vinay Malhotra, MD, a cardiologist at MultiCare’s Pulse Heart Institute. “If a person has elevated Lp(a) levels, it has nothing to do with their diet or lifestyle — they just inherited it.”

About one in five people inherit elevated levels of Lp(a), but they may not know it because it’s not part of a standard lipid panel, and it’s not common to test for it.

“The reason many doctors don’t test people for elevated Lp(a) is that we don’t have good therapies to treat it and bring those levels down,” Dr. Malhotra says. “While statins can lower triglycerides and cholesterol, they don’t make a substantial difference in lowering Lp(a).”

Should you get tested for Lp(a)?

Dr. Malhotra recommends talking to your doctor or other health care provider about Lp(a) testing if you:

• Have a family history of premature coronary artery disease
• Are in your 40s or 50s and have experienced a heart attack (myocardial infarction)

A clinical trial offers hope for lowering Lp(a) levels

After reading about Lp(a), Tran consulted with his doctor and they decided to test him for it. Sure enough, his Lp(a) levels were elevated.

Now that he had identified the likely culprit of his heart attack, a new question arose: Given the lack of treatments available for high Lp(a), what could he do to lessen his risk of having another cardiac event?

Tran’s doctor referred him to a clinical trial testing an investigational drug that may reduce Lp(a) levels at the MultiCare Institute for Research & Innovation.

“Lp(a) is made in the liver, and it’s assembled from smaller particles,” says Dr. Malhotra, principal investigator of the trial. “If you think of Lp(a) as a Lego set, the aim of this drug is to disrupt the assembly of its pieces. If Lp(a) particles can’t be assembled, then the levels of Lp(a) circulating in the bloodstream naturally go down.”

In previous rounds of study, the drug demonstrated both safety and efficacy. Now Dr. Malhotra and his co-investigators want to further confirm its effectiveness by comparing it to a placebo (a product that looks the same as the investigational drug but contains no active medication).

The trial is both double-blind and randomized, which means that participants are assigned by chance to one of two groups: one receives the investigational drug while another receives the placebo.

In this type of study, neither the trial participants nor the investigators know who is assigned to which group until the trial is over. This study design allows investigators to accurately compare treatments and helps eliminate potential bias. Participants in the placebo group will have access to the investigational drug once the trial is complete.

Across the nation, this multicenter trial enrolled approximately 7,000 patients. Many people traveled to the Research Institute study site in Puyallup from neighboring states to participate. While enrollment has closed, the study is ongoing.

“We are on the cusp of a turning point for people with elevated Lp(a) levels,” Dr. Malhotra says. “This drug is part of a whole new class of medications in development that will likely enable us to personalize treatment for this population, helping to prevent cardiac events from happening.”

Like the other participants, Tran does not know whether he is receiving the investigational drug or placebo, but his motivation for participating extends beyond his own well-being.

“My children have elevated Lp(a) levels too,” he says. “So if this drug proves successful, my hope is that one day they can take it so they don’t have to go through what I did.”