Year in Review: SGLT2 Inhibition, Lipid-Lowering Make Waves in Clinical Cardiology in 2019

Trials of the sodium glucose co-transporter 2 (SGLT2) inhibitors, originally developed as antidiabetic medications, continued to create excitement within the cardiology world throughout 2019, along with studies of novel lipid-lowering therapies.

Both areas were highlighted as two of the major developments over the past year within the broad umbrella of clinical cardiology by Christopher Cannon, MD (Brigham and Women’s Hospital, Boston, MA), and Erin Michos, MD (Johns Hopkins Medicine, Baltimore, MD).

“There were just so many interesting trials this year. I thought it was a great year,” Michos told TCTMD.

Impressive SGLT2 Inhibitor Data

Although the benefits of SGLT2 inhibitors in terms of reducing cardiovascular risk in patients with type 2 diabetes have been known for a few years, 2019 saw the publication of two trials that broadened the scope of the effects of this class of drugs, Michos said.

The first was CREDENCE, a trial of canagliflozin (Invokana; Janssen) in patients with type 2 diabetes and chronic kidney disease. Results presented at the American Diabetes Association Scientific Sessions and published in the New England Journal of Medicine showed that the SGLT2 inhibitor improved both renal and cardiovascular outcomes. That’s important, Michos said, because other than ACE inhibitors and angiotensin II receptor blockers, no major therapies have been shown to have a meaningful impact on renal outcomes in patients with type 2 diabetes over the past few decades.

When looking that CV benefits of SGLT2 inhibitors, DAPA-HF, a trial of dapagliflozin (Farxiga; AstraZeneca), “takes it to the next level,” she said. That’s because the trial, reported in full at the European Society of Cardiology (ESC) Congress and later published in NEJM, demonstrated that the drug reduced the risk of worsening heart failure events and CV death and improved symptoms in patients with heart failure and reduced ejection fraction, regardless of whether they had diabetes.

The impact outside of diabetes is an “eye-opener,” according to Cannon, and “makes this very much like ACE inhibitors in the sense of the breadth of the benefit in terms of population and on endpoints prevented.”

Cannon noted that these data are already having an impact on practice, with SGLT2 inhibitor prescriptions rising. “It’s slower than one would hope, but there have been so much data that everyone’s paying attention—cardiologists, endocrinologists, primary care [physicians], nephrologists,” he said.

Michos agreed that the impact has been far-reaching: “I think we’ve moved out of the realm of considering these diabetes medications. I consider them cardiovascular prevention drugs and organ protection drugs.”

Shifts in Treatment of Lipids

Both Michos and Cannon singled out lipid management as an area that experienced significant developments over the past year.

Cannon pointed to new European guidelines that pushed for a lower-is-better and risk-based approach to managing patients with high LDL cholesterol. He called the recommendations “awesome,” adding that “they’re simple, evidence-based, and aggressive in adopting the new trial data.” Specifically, he was supportive of the move to recommend an LDL cholesterol goal of less than 55 mg/dL for very-high-risk patients.

“I’m hoping that the [American College of Cardiology/American Heart Association (ACC/AHA)] guideline, which made a lot of progress, could look at how simple the ESC one is and morph a little bit towards the simplicity of that guideline,” Cannon said.

Over the past year, icosapent ethyl (Vascepa; Amarin) has continued to gain traction for lipid management. REDUCE-IT, showing that the prescription fish oil prevents CV events in patients with high triglycerides, was first published last year, but new analyses looking at its impact on total events and its cost-effectiveness (it was, in fact, cost-saving) were released in 2019.

“That’s great news that we’ll have a therapy that won’t be blocked so much by the insurance companies and provides a huge benefit for patients,” Cannon said. “I’ve also been impressed/depressed at how many patients have high triglycerides despite effective LDL control, and so this, too, applies to many of our patients here in the US and worldwide.”

Michos also mentioned the new REDUCE-IT data, but pointed out that insurance coverage remains a barrier to use of the therapy for some patients. “I’ve been trying to use a lot more icosapent ethyl after REDUCE-IT was published last year, and I still run into problems with burdensome [preauthorizations],” she said, adding that she hopes the cost-effectiveness data will aid in addressing that problem.

And finally, both Michos and Cannon expressed excitement about ongoing developments in new lipid-lowering therapies—in particular, bempedoic acid, which is being developed by Esperion, and inclisiran, which is being developed by The Medicines Company. The former drug proved successful in lowering LDL cholesterol in statin-treated patients in the CLEAR Wisdom and CLEAR Harmony trials, and the latter showed reductions in LDL cholesterol in the ORION series of studies.

Michos said trials demonstrating effects on hard clinical outcomes are still needed, but indicated that there remains a need for additional lipid-lowering therapies. Inclisiran is promising, she said, because it is delivered by injection just twice a year. And she said bempedoic acid is interesting because it is an oral agent and would likely be much cheaper than either inclisiran or the PCSK9 inhibitors.

“I’m excited because for years we really didn’t have anything but statins and then ezetimibe. And then we had the PCSK9 monoclonal antibodies, but they’re so expensive—even with the price reduction they’re still $6,000 a year. So to have more options for LDL-lowering I think is going to be really great progress for patients,” Michos said. “The jury is still out, but I’m really watching this space closely. I think it’s really exciting. Big year for lipids.”

Dropping Aspirin and More

Several other developments shaped cardiology in 2019 as well, according to Michos and Cannon. Here are some of the highlights:

• New prevention guidelines from the ACC and AHA pulled back on recommendations for aspirin, among other advice.
• The PARTNER 3 and Evolut TAVR in Low-Risk Patients trials established a place for transcatheter aortic valve replacement in low-risk patients.
• ISCHEMIA showed that an invasive strategy was no better than optimal medical therapy in terms of hard clinical outcomes in patients with stable, moderate-to-severe coronary disease, but that revascularization was better at improving angina. “It’s nice to have those data to reaffirm the importance of medical therapy, and then you use revascularization when you need to,” Cannon said.
• Low-dose colchicine cut the risk of ischemic CV events in patients with a prior MI in the COLCOT trial, validating the inflammatory hypothesis, according to Michos.
• The TWILIGHT trial showed that ticagrelor (Brilinta; AstraZeneca) monotherapy after 3 months of dual antiplatelet therapy (DAPT) lessens bleeding without increasing ischemic events after PCI compared with continuing DAPT.