Rosuvastatin Bests Atorvastatin for Reducing CVD Risk: Registry Data

A head-to-head comparison of two popular lipid-lowering medications suggests that rosuvastatin may be a better option than atorvastatin when it comes to decreasing the risk of all-cause mortality and cardiovascular events, a new retrospective study shows.

In two large databases—the China Renal Data System (CRDS) and UK Biobank—treatment with rosuvastatin lowered the relative risk of all-cause mortality by as much as 26% when compared with atorvastatin and lowered the risk of major adverse cardiovascular events by as much as 29%, report investigators.

“These findings emphasize that some of the clinical outcomes associated with starting rosuvastatin treatment differ from the clinical outcomes associated with starting atorvastatin treatment, and clinicians might want to consider these differences when prescribing one of these drugs to individual patients,” Shiyu Zhou, MD (Nanfang Hospital/Southern Medical University, Guangzhou, China), and colleagues write in their paper published last week in the Annals of Internal Medicine.

Atorvastatin, known commercially as Lipitor, was first approved for lowering LDL cholesterol in 1996 and lost patent protection in 2011. Crestor, the brand name of rosuvastatin, was approved in 2003 and went off patent in 2016. At the time of its approval, rosuvastatin was heralded as a super statin for its ability to lower LDL-cholesterol levels.

Stephen Nicholls, MBBS, PhD (Monash University, Adelaide, Australia), who led the SATURN imaging study comparing atorvastatin and rosuvastatin, said the larger reduction in LDL cholesterol seen with rosuvastatin should ultimately translate into fewer cardiovascular events.

There was, however, a higher risk of diabetes with rosuvastatin, he noted, which is also in line with prior studies showing that the diabetes risk is heightened with more potent statins.

“The SATURN study demonstrated similar effect on plaque progression with the highest doses of both rosuvastatin and atorvastatin, as evidenced by change in percent atheroma volume, while there did seem to be more regression of total atheroma volume with rosuvastatin,” he told TCTMD. “So, the findings are complementary. A potentially favourable effect on plaque translating to a longer-term effect on cardiovascular events in the real world.”

Nicholls, who wasn’t part of the study, stressed that both rosuvastatin and atorvastatin are “very good and potent statins” effective for managing cardiovascular risk.  

MACE, Liver Outcomes, and Diabetes

The study included 239,970 patients in the CRDS database who started atorvastatin or rosuvastatin between 2012 and 2022, as well as 45,710 patients in the UK Biobank who started either drug between 2006 and 2010. In CRDS, there were 169,357 news users of atorvastatin and 70,613 new users of rosuvastatin, while the vast majority of patients in the UK Biobank were treated with atorvastatin (n = 42,577).

After propensity matching, there were 67,189 new users of atorvastatin or rosuvastatin in CRDS and 2,984 new users in the UK Biobank. The majority of patients in both databases (61%) were treated for secondary prevention. The median age was 64 years, and roughly 54% were male. The median LDL cholesterol at baseline was roughly 108 mg/dL in the CRDS and 148 mg/dL in the UK Biobank.

In CRDS, the all-cause mortality event rates per 100 person-years were 2.57 and 2.83 with rosuvastatin and atorvastatin, respectively. In UK Biobank, the event rates per 100 person-years were 0.66 and 0.90, respectively. This translated into 9% and 26% lower risks of all-cause mortality with rosuvastatin in the two respective databases. The MACE event rates per 100 person-years were 2.20 and 2.48 with rosuvastatin and atorvastatin, respectively, in the CRDS and 0.82 and 1.14 in the UK Biobank. This translated into relative 11% and 29% reductions in MACE risk favoring rosuvastatin in CRDS and UK Biobank.

Major adverse liver outcomes were significantly reduced with rosuvastatin, while there was no significant difference in the risk of developing chronic kidney disease. The risk of developing type 2 diabetes—a known side effect of statin use—was 25% higher with rosuvastatin in the UK Biobank, but there was no signal of harm seen in the CRDS. Statin-related side effects did not differ between treatments in either database.

The researchers emphasize that the absolute differences between drugs were relatively small and there is the potential risk of residual confounding.    

Kausik Ray, MD (Imperial College London, England), who wasn’t involved in the study, said that although investigators attempted to eliminate confounding through propensity matching, it’s not fully known why or when medications were started, something that might impact clinical outcomes.

Additionally, he doesn’t think investigators compared similar-potency statins based on doses, saying it was not a “like-for-like comparison.” Most patients (87.5%) started on rosuvastatin received 10 mg or less, while 95% of atorvastatin-treated patients were started on 20 mg or less. He added that there are data showing similar benefits across statins based on the standardized 1-mmol/L reduction in LDL cholesterol used by Cholesterol Treatment Trialists’ Collaboration.

In other words, “what matters is the absolute [LDL]-lowering,” said Ray in an email.