Rosuvastatin, Atorvastatin: Similar effects in LODESTAR, Some signals differ

This secondary analysis showed more diabetes and cataracts but rosuvastatin reduced LDL cholesterol more effectively.

According to a secondary analysis of the LODESTAR trial, among people with CAD, both rosuvastatin and atorvastatin were similarly effective against the composite of all-cause death, myocardial infarction, stroke, or any coronary revascularization within 3 years. Notably, although the former has been linked to lowering LDL cholesterol, it has also been linked to a higher risk of new-onset diabetes and cataract surgery.

Presented at the 2023 American College of Cardiology meeting, LODESTAR’s main findings demonstrated that a treat-to-target approach involving statins was non-inferior to the guideline-recommended high-intensity strategy in reducing the risk of major adverse cardiovascular events.

The secondary analysis of this statin-focused trial will not only be useful to physicians in optimizing their practice in the management of dyslipidemia but also to the general population in providing Insight into regular testing of blood sugar, HbA1c and cataracts. [that] should be considered when they are taking high-potency statins, senior author Myeong-Ki Hong, MD, PhD (Yonsei University of Medicine, Seoul, Korea), told TCTMD in an email.

According to Derek Connolly, MBChB, PhD (Birmingham City Hospital, UK), who commented on the research on TCTMD, the marketing of these drugs before they become generic may lead some people to believe that rosuvastatin is better than atorvastatin. However, I think the LODESTAR studies tell us there’s probably not a big difference between them, he said.

Secondary analysis results

As for the new analysis, published yesterday in the journal BMJ, Yong-Joon Lee, MD (Yonsei University School of Medicine), Hong and colleagues included 4,341 Korean patients from the original trial (median age 65 years; 27.9% women) randomized to receive atorvastatin or rosuvastatin.

After 3 years, the mean daily dose was higher in the rosuvastatin group than in the atorvastatin group (17.1 vs 36.0 mg; P < 0.001). Additionally, fewer patients in the rosuvastatin group also received ezetimibe.

The primary composite outcome of all-cause death, myocardial infarction, stroke, or any coronary revascularization at 3 years did not differ between drugs, occurring in 8.7% of the rosuvastatin and rosuvastatin cohorts. 8.2% in the atorvastatin group (HR 1.06; 95% CI 0.86). -1.30). There were no differences between study groups on any of these endpoints, individually.

Mean LDL cholesterol was lower in patients treated with rosuvastatin than in patients treated with atorvastatin (1.8 vs 1.9 mmol/L; P < 0.001), but more former patients reported new-onset diabetes requiring antidiabetic medication (7.2% vs 5.3%; HR 1.39; 95% CI 1.03- 1.87) and cataract surgery (2.5% vs 1.5%; HR 1.66; 95 %CI 1.07-2.58). There were no differences between study groups for all other safety endpoints.

Finally, a post-hoc analysis using the definition of new-onset diabetes as having a hemoglobin A1c concentration of at least 6.5% during the study period still showed a higher incidence in those treated with rosuvastatin vs atorvastatin (9.5% vs 7.7%; HR 1.25). ; 95% CI 1.02-1.53).

Hong called all the results surprising given the lack or anecdotal clinical data in this field. The primary finding of comparable cardiovascular benefits between the two statins and the secondary finding of [slight] differences in LDL cholesterol levels [achieved]“The need for high-intensity statins or ezetimibe, new-onset diabetes requiring medication, and cataract surgery are all important findings that could impact our clinical practice,” he said. .

Hong said he took all of this into account to optimize my dyslipidemia treatment by considering risk factors for each patient. For example, if a patient definitely needs a stronger reduction in LDL-cholesterol levels, a certain statin may be preferred. On the other hand, if a patient’s LDL levels are well managed but they have impaired fasting blood sugar, another statin may be preferred.

While the data may be considered for future cholesterol guidelines, Hong said he believes more data will be needed to change the guidelines.

Statins have only one building block

Furthermore, although there may be small differences between the drugs, the statin monotherapy strategy is no longer the preferred approach, Connolly argues, data citation Supports the benefits of combination therapy including drugs such as bempedoic acid (Nexletol; Esperion), ezetimibe, a PCSK9 inhibitor, and inclisiran (Leqvio; Novartis). Statins are just one of the basic components and I think that hasn’t really been emphasized in [LODESTAR] papers, he said.

The bottom line, however, is that, overall, this is not a surprising test, Connolly said. [It] would likely lead most clinicians to choose atorvastatin over rosuvastatin despite the minimal differences. It won’t change my practice at all because I already prefer atorvastatin, and I like most of the world. [already] are doing it.

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