Article Image

The Best and Worst of Times at the 2023 ACC Conference

Op-Med is a collection of original articles contributed by Doximity members.

Dr. Edward Fry set a bittersweet tone for the 2023 American College of Cardiology conference with a quote from Charles Dickens in his keynote address: “It was the best of times, it was the worst of times.” He cited the country’s declining life expectancy throughout the COVID-19 pandemic as an example of how it was the “worst of times.” Yet, the conference represented how it was simultaneously “the best of times.” The research and technologies in cardiovascular care presented at the meeting promised a better, healthier future. This comeback spirit resonated with the location of New Orleans, which famously had recovered from another natural disaster much earlier when Hurricane Katrina hit in 2005. 

Among the late-breaking clinical trials of the conference were two studies supporting new drugs for cholesterol reduction. Statins have long been the standard medication utilized to lower cholesterol, particularly low-density lipoprotein (LDL). However, many patients experience intolerance to statins with myalgias, cognitive impairment, and diabetes. Alternatives to statin therapies up until now have included ezetimibe, bile acid sequestrants, and oral PCSK9 inhibitors, which are not without their concerns. Bile acid sequestrants, for example, can be associated with gastrointestinal distress and hypertriglyceridemia. Given that approximately 1 in every 10–12 patients experience statin intolerance, the need for alternative lipid-lowering therapies at this time is highly imperative. 

One of these studies supporting alternative lipid-lowering agents was the CLEAR trial, which examined bempedoic acid’s effects in LDL reduction. Presented by study chair Dr. Steve Nissen, the study was a multi-center, international, randomized control trial of 13,970 participants with proven statin intolerance. They were randomized to either 180 mg daily of bempedoic acid or placebo. Bempedoic acid inhibits hepatic cholesterol synthesis upstream of HMG-CoA reductase, which is the enzyme inhibited by statins. Because bempedoic acid is a pro-drug activated in the liver but not in peripheral tissues, its adverse effects compared to statins are theoretically fewer. In the study, participants were followed for at least 24 months, with a median follow-up of 40.6 months. The primary composite endpoint of nonfatal myocardial infarction, stroke, coronary revascularization, or cardiovascular death was 13% lower among patients receiving bempedoic acid. Rates of myocardial infarction were reduced by 23% and coronary revascularization by 19%. Importantly, bempedoic acid was also associated with a decrease in LDL by as much as 21.7% at six months follow-up and a decrease in hs-CRP with a reduction by 22.2% at six months. Despite these outcomes in favor of bempedoic acid, there was no difference between treatment groups in all-cause and cardiovascular-related mortality. No differences in most adverse events were observed, although the bempedoic acid group did experience a slightly higher rate of gout in 3.1% of patients and cholelithiasis in 2.2% of patients. Results from the CLEAR trial were simultaneously published in The New England Journal of Medicine. 

The second trial demonstrating efficacy of non-statin lipid-lowering therapy assessed an oral PCSK9 inhibitor, MK-0616. Injectable PCSK-9 inhibitors reduce LDL by as much as 43% to 64% and are recommended in the ACC/AHA guidelines for patients with elevated cholesterol that is refractory to treatment with statin or ezetimibe. However, injectable PCSK9 inhibitors can be associated with discomfort at the injection site and carry a high cost. In this Phase 2b trial, presented by the study’s lead author Dr. Christie Ballantyne, 381 patients were randomized to receive MK-0616 at various doses or placebo. At eight weeks, there was a significant percent change in LDL from baseline seen across all doses of MK-0616. Among patients receiving the lowest dose of the treatment drug, a 41.2% difference was seen in percent LDL reduction compared to the placebo group. Rates of adverse events at 16 weeks were similar among groups. The size of the trial was relatively small, and clinical outcomes related to cardiovascular events and mortality were not assessed in this study. Nevertheless, the trial suggested that the benefits of injectable PCSK9 inhibitors in lowering LDL carry over into the oral formulation as well. Results from the study were published in the Journal of the American College of Cardiology. 

Together these two late-breaking clinical trials offer a glimpse into “the best of times” in cardiology care. In addition to their scientific breakthroughs, nearly half the participants in both trials were women. The CLEAR trial, and Phase 2b study of oral PCSK9 inhibitors provide hope that new medications will soon be added to the armamentarium of cardiologists seeking alternative lipid-lowering therapies for their patients with statin intolerance.

Dr. Haghighat has no conflicts of interest to declare.

Image by ya_blue_ko / Shutterstock

All opinions published on Op-Med are the author’s and do not reflect the official position of Doximity or its editors. Op-Med is a safe space for free expression and diverse perspectives. For more information, or to submit your own opinion, please see our submission guidelines or email

More from Op-Med