Pharma thinks it’s found the next frontier in preventing heart attacks. 

Novartis, Amgen and Eli Lilly are among the drugmakers betting that slashing levels of a particularly bad form of cholesterol could deliver the next blockbusters in cardiology. All three of the pharmaceutical giants are in late-stage trials to test whether drugs that cut Lp(a) can protect people from heart attacks.

If they can, the opportunity could be massive: an estimated one in five people worldwide have elevated Lp(a), and there’s not much they can do to lower it. Evidence from human genetics suggests the idea could work, but drugmakers don’t know for sure. That makes the first late-stage trial results from Novartis, expected later this year, important for the entire pipeline. 

“History has taught us you can’t make assumptions,” said Dr. Steve Nissen, chief academic officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic who is the principal investigator of Novartis’ Phase 3 Horizon trial of pelacarsen, the company’s experimental drug to lower Lp(a). “We thought raising HDL would be beneficial and that didn’t work, so I think we have to keep an open mind.”

Lp(a), or lipoprotein(a), was first discovered in 1963. It’s a more dangerous cousin to the well-known LDL cholesterol because it simultaneously clogs arteries and promotes blood clots, posing two risks with just one particle. Almost 50 years after Lp(a) was discovered, researchers found that people who have high levels of it had a more than twofold higher risk of heart attack than those who don’t. 

How much Lp(a) a person has circulating in their body is almost entirely determined by their genes. Lifestyle factors like diet and exercise don’t influence Lp(a) levels like they do LDL levels, leaving people with few good options to reduce it. 

Currently, doctors encourage people to focus on the factors they can change, such as lowering their LDL cholesterol, decreasing blood pressure, treating obesity and diabetes and exercising. Those strategies can help protect people from high Lp(a) for some time, Nissen said. New medicines could treat people for a longer time. 

Novartis, Amgen and Lilly have already proven their experimental drugs slash levels of Lp(a) by more than 80%. Now, they will need to show that translates into tangible benefits. If that happens, the drugs could reach annual sales of $5.6 billion by 2032, according to consensus estimates from Evaluate, a pharmaceutical commercial intelligence firm.

“We don’t know how much you have to lower levels,” Nissen said. “We don’t know how high you have to be to benefit from getting your level lowered. Estimates of how much you have to lower levels to prevent events based upon genetic studies are highly variable, so we don’t have an answer, and we won’t have an answer until on the date that we unblind the trial.”

That should happen around the middle of the year, Novartis CEO Vas Narasimhan said on the company’s fourth-quarter earnings call in February….

Investor Insight

Cardiol Therapeutics is positioned with a late-stage lead asset, multiple orphan indications, strong clinical proof-of-concept data, and a differentiated non-immunosuppressive approach to inflammatory heart disease. The company’s 2025–2026 catalysts – MAVERIC Phase III enrollment progress, full ARCHER data, and CRD-38 clinical initiation – are key value drivers in large and underserved cardiovascular markets.

Overview

Cardiol Therapeutics Inc. (NASDAQ:CRDL,TSX:CRDL) is a clinical-stage life sciences company focused on the research, development, and commercialization of innovative anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease. The company’s programs target serious, often life-threatening cardiovascular conditions for which there are limited or no approved treatments, including recurrent pericarditis, acute myocarditis, and heart failure.

Cardiol’s therapeutic approach centers on modulating inflammasome pathway activation—a central driver of inflammation and fibrosis in the heart. This is achieved through pharmaceutically manufactured cannabidiol formulations developed under cGMP standards. Cannabidiol has been shown in preclinical and clinical studies to down-regulate inflammatory mediators (e.g., IL-1, IL-6) and preserve cardiac structure and function, offering the potential for disease-modifying, non-immunosuppressive treatment options.

The company’s lead oral drug candidate, CardiolRx, is in late-stage clinical development:

Cardiol is also advancing CRD-38, a proprietary subcutaneous cannabidiol formulation for heart failure. IND-enabling studies are underway following compelling preclinical results showing cardioprotection through preservation of mitochondrial function and prevention of cardiac remodeling.

What it is: A pivotal clinical program testing CardiolRx in patients with recurrent pericarditis, a painful and debilitating inflammation of the membrane around the heart that often returns despite prior treatments. The condition can cause severe chest pain, shortness of breath, and repeated hospitalizations.

Why it matters: Current third-line therapy is costly, immunosuppressive and associated with a high recurrence rate after discontinuation. CardiolRx offers the potential for a non-immunosuppressive, disease-modifying option.

Status:

• Completed MAvERIC-Pilot Phase II: Rapid and durable reductions in pain and inflammation sustained over 26 weeks; majority of patients recurrence-free during extension.
• Phase III MAVERIC trial: Multinational, double-blind, placebo-controlled study enrolling 110 high-risk patients across ~20 sites in North America and Europe. Primary endpoint: recurrence-free rate at 24 weeks after IL-1 blocker discontinuation.

What it is: A global Phase II trial evaluating CardiolRx in acute myocarditis, an inflammatory heart…

Billionaire Ray Dalio, founder of Bridgewater Associates, is sounding the alarm on America’s chronic spending, national debt nearing $37 trillion, combined with a $2 trillion deficit that may balloon with President Trump’s ‘One Big Beautiful Bill.’ 

“We’re spending 40% more than we’re taking in and this is a chronic problem. So what you’re seeing is the debt service payments beginning to squeeze away, not beginning, well into squeezing away. So it’s like plaque in the arteries squeezing away buying power. And as you can do the numbers you will see that you can have an economic heart attack as a result of that That we’re going to very soon get to the position that you need debt to pay the debt,” said Dalio on FOX Business Network’s ‘The Claman Countdown.’

NEARLY ONE-THIRD OF $36T NATIONAL DEBT NEEDS REFINANCING AS TRUMP DEMANDS RATE CUTS

Dalio also outlined a pathway to ease the economic credit crunch. 

“We are at a juncture right now that, if we can, soon, very soon, while the economy is still good, cut the deficit to 3% of GDP, which is possible. You only have to change a couple of things, change spending by four percent, change tax income by four percent, then you’ll have a lower interest rate as a result. This is possible. It was done between 1991 and 1998, that balance, if everybody gives a little bit, there’s a possibility of being able to get it down to 3%. If you don’t do that, and we probably won’t do that, It is like the plaque building in the heart. And so we are now then going to have not only more debt and more debt service encroaching on our spending, But it’s also going to mean that we’re going to have a supply-demand problem,” he said. 

DALIO ON THE U.S.: GOING BROKE?

CAN AND WOULD TRUMP FIRE FED CHAIR POWELL?

The Congressional Budget Office estimates Trump’s tax bill could lift the deficit to $2.77 billion. The White House has pushed back on the CBO’s scoring and estimates, saying it doesn’t factor in revenues, including what tariffs are bringing in. Former Trump economic Advisor Larry Kudlow, now host of FOX Business Network’s ‘Kudlow,’ has also pointed out the CBO has a history of missing the mark and “under-reported” the first go-round of Trump’s 2017 tax cuts by $2.3 trillion over the past seven years. 

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The bill continues to make its way through Congress and is expected to be on the President’s desk by July 4.