Year in Review: New Guidelines, Inclisiran, Dapagliflozin Impact CVD Prevention in 2019

The biggest cardiology news in the prevention space for 2019 included new primary prevention guidelines, promising drugs like dapagliflozin and inclisiran, and a better understanding of aspirin in clinical practice, according to two experts.

“All in all, I would say 2019 has been a great year for prevention,” Kavitha M. Chinnaiyan, MD (Beaumont Health, Royal Oak, MI), told TCTMD. “It’s made us think outside of the box in terms of understanding the pathophysiology of disease; the social, economic, cultural, and ethnic issues associated with cardiovascular disease; and how we need to train the community of cardiologists to start thinking about this.”

She pointed first to the March publication of the American College of Cardiology/American Heart Association (ACC/AHA) primary prevention guidelines as a refreshing take on the field.

 “They speak a lot about how we are actually now viewing prevention as a very important aspect of cardiology—not that it wasn’t before, but now there is a paradigm shift,” Chinnaiyan said. “We can have a lot of guidelines and we can say a lot about prevention, but when it comes down to it, it’s whether or not the patient is able to do that, to make the lifestyle changes and to afford medications. . . . In the past, we’ve kept prevention separate from the social, cultural, economic arenas of society and now they’re coming together, which they should. If we're going to talk about population medicine, precision medicine, and how they work together, we can’t ignore these factors.”

On the drug front, Chinnaiyan pointed to the ORION trials looking at inclisiran, an investigational, twice-yearly small interfering RNA (siRNA) injectable as very important. “This has shown so much promise,” she said. “Of course, the PCSK9 inhibitors are a big deal this year with so many trials coming out, and suddenly now we have agents that patients are able to tolerate. Whether or not they can afford it is another thing, but now we have the possibility of one or two doses per year, which is an incredible advancement in this arena.”

When it comes down to it, it’s whether or not the patient is able to do that, to make the lifestyle changes and to afford medications. Kavitha M. Chinnaiyan

Philip Greenland, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), agreed about the exciting potential of inclisiran. The results achieved with it so far are “quite impressive and the early findings with inclisiran are that it looks like it is very safe, but there's a lot of caveats,” he said. “The information that we have so far is short-term, it's really only biomarkers, . . . and nobody in cardiology anyway gets excited anymore about LDL-lowering—it's all about events. So we need to get the event information, which won't be out for a while longer, and we also need to know that on a longer-term basis that the drug is safe. But at least what I hear in conversations with colleagues is that it is considered to be one of the most exciting developments in the area of prevention, which could have an implication for high-risk primary prevention patients.”

However, for Greenland, his highlights of the year centered around secondary prevention.

Icosapent ethyl (Vascepa; Amarin), may have made its splash in 2018, but this year brought the presentation of the REDUCE-IT subanalysis showing the prescription omega-3 fatty acid formulation reduces total cardiovascular events by 30% in statin-treated patients with high triglyceride levels and either established cardiovascular disease or diabetes plus risk factors. Moreover, an expanded labeling for the drug was just approved last week by the US Food and Drug Administration to cover the cardiovascular event reduction.

“The real breakthrough would be if a drug like that lowered risk in primary prevention patients and it could be that in people with high triglycerides or low HDL that that might work,” Greenland commented. “There are trials that are being conducted in those kinds of patients, but still waiting. It's in the category of ‘looks pretty good so far’ with a limited use, but could be a much more expanded use and that would be pretty exciting.”

He also pointed to the DAPA-HF study, which showed marked reductions in the risk of worsening heart failure events and cardiovascular death, as well as symptom improvement when dapagliflozin was added to standard therapy in heart failure patients with reduced ejection fraction with and without diabetes. The drug is currently approved to improve glycemic control in type 2 diabetes and to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors; DAPA-HF opens up the possibility of an indication beyond diabetes.

“That would be really exciting because aside from blood pressure-lowering treatment, we just don't have very much for heart failure prevention, so this would be really potentially quite a big deal,” Greenland explained.

Lastly, he brought up the COLCOT trial, which was presented at the AHA meeting in November and showed that colchicine—an anti-inflammatory agent indicated for gout and pericarditis—can lower the risk of ischemic cardiovascular events in MI patients.

“It really plays into the whole story about the role of inflammation in coronary disease patients,” Greenland said, noting that the 2017 CANTOS trial was exciting but limited by the high expense of canakinumab and other factors. On the other hand, colchicine is “a ridiculously cheap drug that's been around for forever, . . . and there are trials showing that it's effective for preventing recurrences of pericarditis and so it's had a use in cardiology already. It looks like with this colchicine trial that this will be another potential mechanism to lower risk after MI,” he predicted.

Chinnaiyan pointed to some additional news items centered around prevention in 2019:

• Several aspirin trials that were published in 2018 as well as studies like TWILIGHT have helped further delineate the role of this drug in both primary and secondary prevention. “This has been a good year for understanding this and shaping how we are going to talk about aspirin with our patients,” she said.
• As an imager, Chinnaiyan also brought up the ongoing conversation around calcium scoring. “The power of zero has also become a real important thinking point for preventive cardiologists in understanding the economics of health care. Can we as a society afford to put people on statins if they don't need it and if patients can’t afford it?”
• This paper published in the Journal of the American College of Cardiology addresses the possibility of preventive cardiology as its own subspecialty. “This is an exciting field, and this has come about because of these trials, because of these new advances in prevention,” she said. “There is so much more we can do than just send people to surgery or to the cath lab or put them on medications.”