Rosuvastatin, Atorvastatin: Similar Efficacy in LODESTAR, Some Differing Signals

Among those with CAD, both rosuvastatin and atorvastatin are similarly effective regarding the combination of all-cause death, MI, stroke, or any coronary revascularization over 3 years, according to a secondary analysis of the LODESTAR trial. Notably, while the former was associated with lower LDL cholesterol, it also was linked to greater risks of new onset diabetes and cataract surgery.

Presented at the American College of Cardiology 2023 meeting, the main LODESTAR findings demonstrated that a treat-to-target approach regarding statins is noninferior to the guideline-recommended high-intensity strategy with regards to reducing the risk of major adverse cardiovascular events.

“This secondary analysis of the trial which focused on statin type will be helpful not only for physicians to optimize their practice in dyslipidemia management but also for the general population in providing insight regarding regular check-ups for blood glucose, HbA1c, and cataracts [that] should be considered when they are taking high-potency statins,” senior author Myeong-Ki Hong, MD, PhD (Yonsei University College of Medicine, Seoul, Republic of Korea), told TCTMD in an email.

Prior marketing of these drugs before they became generic likely led some to believe that rosuvastatin is “better” than atorvastatin, according to Derek Connolly, MBChB, PhD (Birmingham City Hospital, England), who commented on the study for TCTMD. However, “I think the LODESTAR studies tell us there probably isn't any major difference between them,” he said.

Secondary Analysis Findings

For the new analysis, which was published yesterday in the BMJ, Yong-Joon Lee, MD (Yonsei University College of Medicine), Hong, and colleagues included 4,341 Korean patients from the original trial (mean age 65 years; 27.9% women) who were randomized to receive atorvastatin or rosuvastatin.

At 3 years, mean daily dose was higher in the rosuvastatin group compared with those on atorvastatin (17.1 vs 36.0 mg; P < 0.001). Also, fewer patients in the rosuvastatin group were also taking ezetimibe.

The primary combined outcome of all-cause death, MI, stroke, or any coronary revascularization at 3 years was no different between agents, occurring in 8.7% of the rosuvastatin cohort and 8.2% in the atorvastatin arm (HR 1.06; 95% CI 0.86-1.30). There were no differences between the study groups for any of these endpoints, individually.

Mean LDL cholesterol was lower for rosuvastatin-treated patients compared with those on atorvastatin (1.8 vs 1.9 mmol/L; P < 0.001), but more of the former patients reported both new-onset diabetes requiring antidiabetic drugs (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 the study groups for all other safety endpoints.

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

Hong called all of the results surprising given the lack or randomized clinical data in this space. “The primary finding of comparable cardiovascular benefits between the two statin types, and secondary findings of a [slight] difference in LDL-cholesterol level [achieved], requirement of high-intensity statins or ezetimibe, new-onset diabetes requiring medications, and cataract surgery were all important findings which will possibly affect our clinical practice,” he said.

Hong said he takes all of these into account to “optimized my practice in dyslipidemia management by considering risk factors for each patient. For example, if the patient surely requires more intensive lowering of LDL-cholesterol levels, certain type of statin may be preferred.” On the other hand, if the patient’s LDL levels are well-managed, but they have impaired fasting glycemia, “the other type of statin may be preferred.”

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

Statins Only One ‘Building Block’

Moreover, though there may be subtle differences between the drugs, a strategy of statin monotherapy is no longer the preferred approach, Connolly argued, citing data supporting the benefits of combination therapy including drugs like bempedoic acid (Nexletol; Esperion), ezetimibe, PCSK9 inhibitors, and inclisiran (Leqvio; Novartis). “Statins are only one of the building blocks, and I think that's not really emphasized in the [LODESTAR] papers,” he said.

“The bottom line though, overall, is that this isn't a surprising trial,” Connolly said. “[It] will probably lead to most clinicians choosing atorvastatin over rosuvastatin even though there are minimal differences. It won't change my practice at all because I was already favoring atorvastatin, and I and most of the world were [already] doing that.”