November 20, 2023
3 minute read
Important points:
- In patients with statin intolerance, inflammatory risk contributed more to mortality and cardiovascular events than cholesterol risk.
- This result suggests that sensitive C-reactive protein measurements may benefit patients.
PHILADELPHIA ā Inflammation was a stronger predictor of risk of CV events and death than cholesterol in the CLEAR Outcomes cohort of statin-intolerant patients, researchers reported at the American Heart Association Scientific Sessions.
A new analysis was published at the same time CirculationAs previously reported by Healio, bempedoic acid (Nexletol, Esperion Therapeutics) reduced the risk of major CV events by 13% compared to placebo in more than 13,000 patients with statin intolerance and CVD. Based on key findings from CLEAR Outcomes: Additionally, in a pooled analysis of more than 31,000 high-risk patients treated with high-risk statins, residual inflammatory risk assessed by high-sensitivity C-reactive protein was associated with higher risk of CV events than residual cholesterol risk assessed. Shown to better predict death. Due to LDL.
“everyone [is] We are starting to coalesce around this general idea that in the future we need to target both hyperlipidemia and inflammation together. It was very challenging and very interesting. ā Paul M. Ridker, MD, MPH; Eugene Braunwald, director of the Center for Cardiovascular Disease Prevention and professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, told Healio. “One of the issues raised in the original work is that [pooled analysis] Could it be that because everyone was already taking statins, they inadvertently somehow reduced the effects of LDL cholesterol? We did our first analysis with everyone on statins because we didn’t want to undermine the idea that everyone should be on statins. The question was, assuming I was on a statin, what should my next medication be? Should we consider another lipid-lowering drug or should we consider anti-inflammatory therapy? That was the structure of that paper.How to deal with the idea that we have inadvertently decreased [the inflammation hypothesis] We looked only at patients treated with statins and said, “Let’s take a look inside CLEAR Outcomes.” Because it has the same structure as the other three of her exams we looked at. This is a modern trial and everyone is on active treatment. However, by definition, these patients are statin intolerant. ā
For the current CLEAR Outcomes analysis, Ridker et al. enrolled 13,970 patients (mean age 66 years, 48% female) with baseline hsCRP (median, 2.3 mg/L) and baseline LDL (median, 134.5 mg). /dL) into quartiles. .
After six months, bemepdoic acid reduced hsCRP by 21.6% and LDL by 21.1% compared to placebo, according to the researchers.
At a median follow-up of 40.6 months, compared to the lowest quartile of baseline hsCRP, those in the highest quartile had fewer major CV adverse events defined as MI, stroke, coronary revascularization, or CV death. The researchers found an increased risk (HR) of the primary endpoints: mortality rate = 1.43; 95% CI, 1.24-1.65), CV mortality (HR = 2; 95% CI, 1.53-2.61); All-cause mortality (HR = 2.21; 95% CI, 1.79-2.73).
In contrast, compared with the lowest quartile of baseline LDL, patients in the highest quartile had an increased risk of the primary endpoint, albeit to a lesser extent than that seen in the hsCRP analysis ( HR = 1.19; 95% CI, 1.04-1.37), Ridker et al. ) was found to be associated with an increased risk of
According to the researchers, bempedoic acid consistently reduced the risk of CV events compared to placebo at all baseline hsCRP and LDL levels.
“The fundamental finding is that we are still in a situation where inflammation is at least as important.” [as cholesterol level]ā Ridker told Helio. “And, again, when it comes to mortality from cardiovascular disease, which I think is the most important issue, it’s even more important. To me, this is an extension of previous research, but very It’s an important reminder that we certainly want to lower LDL cholesterol, but we need to go beyond that. We need to start taking anti-inflammation seriously.”
In June, the FDA approved low-dose (0.5 mg) colchicine (Lodoco, Agepha Pharma) as the first anti-inflammatory therapy shown to reduce CV risk in patients with residual inflammatory risk.
āThe FDA’s approval of low-dose colchicine is very important because it tells the medical community that this is a drug that we simply don’t use. It has been proven to be effective, so please consider that,ā Ridker told Healio. “[Low-dose colchicine is] Doctors should consider adding it as an adjunct to cholesterol-lowering drugs, not as a replacement for cholesterol-lowering drugs. This drug is not suitable for use in patients with severe renal or liver dysfunction. However, there are many patients with chronic stable atherosclerosis who are already taking statins and perhaps also bempedoic acid and ezetimibe, and who have elevated hsCRP levels. Assuming the patient does not have kidney or liver problems, statins are drugs to consider. This is to reduce risk. ā
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Ridker PM et al. Abstract 303. Presentation location: American Heart Association Scientific Sessions. November 11-13, 2023. Philadelphia.
Disclosure: This research was supported by Esperion Therapeutics. Mr. Ridker reports that he has received institutional research grant support from Amarin, Esperion, Kowa, NHLBI, Novartis, Novo and Nordisk and Pfizer. Agepha, Ardelyx, AstraZeneca, Boehringer Ingelheim, Cardio Therapeutics, Civi Biopharm, Cytokinetics, Eli Lilly, Flame, GlaxoSmithKline, Health Outlook, Horizon Therapeutics, Janssen, Montai Health, NewAmsterdam, Novartis, Novo Nordisk, RTI, SOCAR, Zomagen consulting. He holds shares in Angiowave, Bitteroot Bio, and Uppton. He also receives compensation for services to the Baim Institute, Leducq Foundation, Paris FR, and he Peter Munk Advisory Board (University of Toronto). Please refer to this study for relevant financial disclosures of all other authors.