Design

Objective

To compare the efficacy of rosuvastatin with that of atorvastatin in decreasing low-density lipoprotein (LDL) cholesterol in patients with acute coronary syndrome

Study Groups

Rosuvastatin 20 mg (RSV20; n= 277)

Rosuvastatin 40 mg (RSV40; n= 270)

Atorvastatin 80 mg (ATV80; n= 278)

Inclusion Criteria

Patients aged 18 to 75 years with coronary artery disease and hospitalized for acute coronary syndrome within 48 hours of ischemic symptoms; non–ST-segment elevation acute coronary syndrome and those with ST-segment elevation acute coronary syndrome who received optimal reperfusion therapy (successful treatment with a thrombolytic agent or primary catheter-based intervention initiated within 12 hours of symptom onset); non–ST-segment elevation acute coronary syndrome (non–ST-segment elevation myocardial infarction or unstable angina in whom conservative management was planned); LDL cholesterol level > 70 mg/dL and fasting triglyceride level < 500 mg/dL within 72 hours of symptom onset

Exclusion Criteria

Treatment for dyslipidemia with prescription medication within the preceding 4 weeks; current treatment with a depot formulation of progesterone or initiation of other hormone therapy within the previous 3 months; Q-wave myocardial infarction, pulmonary edema, moderate or severe congestive heart failure, acute moderate to severe mitral regurgitation (3 to 4+), acute ventricular septal defect, occurrence of ventricular fibrillation, sustained ventricular tachycardia, complete heart block, new-onset atrial fibrillation with an uncontrolled ventricular rate, paced ventricular rhythm, stroke, sepsis, acute pericarditis, or any evidence of systemic or pulmonary embolus within the preceding 4 weeks; or failed revascularization during current hospitalization

Methods

Eligible patients who passed the safety screening were randomized (1:1:1) to receive RSV20, RSV40, or ATV80 once daily for 12 weeks. Patients were assessed at weeks 2, 6, and 12 after treatment initiation. 

Duration

December 14, 2003, through August 31, 2007

Follow-up: 12 weeks 

Outcome Measures

Primary: efficacy of RSV20 and RSV40 compared with that of ATV80 in lowering LDL cholesterol averaged over measurements at 6 and 12 weeks 

Secondary: percentage change from baseline in LDL cholesterol and other relevant lipoproteins

Baseline Characteristics

RSV40 (n= 270)

ATV80 (n= 278)

Age, years

Female

White

Body mass index, kg/m²

Type of acute coronary syndrome

ST-segment elevation myocardial infarction

Non-ST-segment elevation myocardial infarction

Unstable angina 

100 (37.0%)

101 (37.4%)

69 (25.6%)

107 (38.5%)

104 (37.4%)

67 (24.1%)

Lipid profile 

Low-density lipoprotein cholesterol, mg/dL

High-density lipoprotein cholesterol, mg/dL

Non–high-density lipoprotein cholesterol, mg/dL

Total cholesterol, mg/dL

Triglycerides, mg/dL 

138.8

38.8

162.8

201.7

182.7

133.2

39.9

156.0

195.9

157.5

Results

Endpoint

RSV40 (n= 251)

ATV80 (n= 257)

p-value

Percentage change in lipid profile 

Low-density lipoprotein cholesterol, mg/dL

High-density lipoprotein cholesterol, mg/dL

Non–high-density lipoprotein cholesterol, mg/dL

Total cholesterol, mg/dL

Triglycerides, mg/dL 

-46.8 ± 18.2

11.9 ± 19.7

-42.6 ± 17.6

-32.2 ± 15.7

-14.6 ± 48.3

-42.7 ± 17.7

5.6 ± 19.1

-39.8 ± 17.4

-30.9 ± 15.1

-18.0 ± 38.7 (n= 254)

< 0.05

< 0.001

Not significant (NS)

NS

NS

LDL cholesterol lowering by RSV20 was similar to that by ATV80. Increases in HDL cholesterol were significantly greater with RSV40 (11.9%, p< 0.001) and RSV20 (9.7%, p< 0.01) than with ATV80 (5.6%). Effects of RSV20 on the secondary parameters were generally similar to those of ATV80.

Adverse Events

Common Adverse Events: RSV 40 vs ATV 80 myalgia (9.1% vs 10%); angina pectoris (8.7% vs 6.7%), noncardiac chest pain (8.4% vs 6.7%); dizziness (4.9% vs 5.6%); headache (3.4% vs 5.9%)

Serious Adverse Events: 8.7% vs 14.1%; serious cardiovascular adverse event (1.9% vs 2.2%); death (0.8% vs 0.4%)

Percentage that Discontinued due to Adverse Events: 6.1% vs 9.3%; musculoskeletal and connective tissue disorders (2.3% vs 6.3%)

Study Author Conclusions

In conclusion, results from the LUNAR study show that RSV40 more effectively decreased LDL cholesterol, increased HDL cholesterol, and improved other blood lipid parameters than ATV80 in patients with acute coronary syndrome.

InpharmD Researcher Critique

As the study had a strict exclusion criterion, including patients with stroke, results may not be readily applicable to the setting of ischemic stroke. Comparative safety and efficacy beyond 12 weeks required further evaluation. 

Efficacy and safety of rosuvastatin 40mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: Results of the POLARIS study

Design

Randomized, double-blind, parallel-group study

N= 871

Objective

Study Groups

Rosuvastatin (n= 432)

Atorvastatin (n= 439)

Inclusion Criteria

Exclusion Criteria

Unstable after a major cardiac event, severe congestive heart failure, known homozygous familial hypercholesterolemia, history of serious or hypersensitivity reactions to other statins, current active liver disease, unexplained serum creatine kinase, serum creatinine > 2.0 mg/dL, uncontrolled hypothyroidism 

Methods

Patients were randomized to be treated with either rosuvastatin 40 mg or atorvastatin 80 mg once daily after titrating up from half the dose over 2 weeks. Additional lipid-lowering therapy may be allowed (excluding statins or fibrates). Fasting blood levels are collected on weeks 0, 8, and 26 after initiation of full dose regimen for lipid analysis. 

Duration

April 2003 to September 2004

Follow-up: 126 weeks after titrating to the full dose

Outcome Measures

Baseline Characteristics

Rosuvastatin (n= 432)

Atorvastatin (n= 439)

Age, years

Male

White

Baseline lipoprotein/lipid levels, mg/dL

LDL-C

TC

HDL-C

TG

non-HDL-C

189.3

275.2

48.0

190.3

227.3

189.0

274.8

47.6

191.3

227.2

HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides.

Results

Endpoint

Rosuvastatin (n= 432)

Atorvastatin (n= 439)

Change from baseline to week 8, mg/dL (95% CI)

LDL-C

TC

HDL-C

TG

Non-HDL-C

-55.9 (-57.3 to -54.4)

-40.4 (-41.5 to -39.3)

+9.6 (7.9 to 11.2)

-22.2 (-25.0 to -19.4)

-50.8 (-52.1 to -49.4)

-52.2 (-53.4 to -50.9)

-39.3 (-40.3 to -38.2)

+4.4 (2.9 to 5.8)

-27.0 (-29.6 to -24.5)

-48.3 (-49.5 to -47.1)

Change from baseline to week 26, mg/dL (95% CI)

LDL-C

TC

HDL-C

TG

Non-HDL-C

-57.0 (-58.5 to -55.5)

-41.2 (42.4 to -40.1)

+11.0 (9.1 to 12.9)

-23.7 (-26.8 to -20.7)

-52.0 (-53.4 to -50.6)

-52.5 (-53.9 to -51.1)

-39.3 (-40.5 to -38.2)

+6.2 (4.6 to 7.7)

-27.7 (-30.5 to -24.8)

-48.7 (-50.1 to -47.4)

CI, confidence interval

Adverse Events

Common Adverse Events: nasopharyngitis (6.3% rosuvastatin group vs. 3.9% of atorvastatin group), myalgia (5.1% vs. 5.9%) and arthralgia (5.8% vs. 4.1%)

Serious Adverse Events: 6.5% rosuvastatin vs. 5.7% atorvastatin

Percentage that Discontinued due to Adverse Events: 5.1% rosuvastatin vs. 6.2% atorvastatin

Study Author Conclusions

InpharmD Researcher Critique

A Comparative Study of High-intensity Rosuvastatin Versus Atorvastatin Therapy Post-acute Coronary Syndrome Using Real-world Data

Design

Retrospective cohort study

N= 1,253

Objective

To compare the effectiveness and safety of 2 high-intensity statin therapies (rosuvastatin vs atorvastatin) in patients with acute coronary syndrome (ACS) postdischarge using real-world data

Study Groups

Rosuvastatin (n= 627)

Atorvastatin (n= 626)

Inclusion Criteria

Age 18-75 years; diagnosed with ACS (ST-elevation myocardial infarction [STEMI], non-ST-elevation myocardial infarction [NSTEMI], or unstable angina [UA]); either statin-naïve or on a low-to-moderate intensity statin therapy prior to admission; discharged on either atorvastatin (40 mg or 80 mg per oral once daily) or rosuvastatin (20 mg or 40 mg per oral once daily)

Exclusion Criteria

Known hypersensitivity to any statin; active liver disease or hepatic dysfunction defined as a level of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) of more than 3 times the upper limit of normal (ULN); pregnancy or breast-feeding; receiving proprotein convertase subtilisin/kexin Type 9 (PCSK9) inhibitor; receiving ezetimibe; already receiving a high-intensity statin prior to ACS diagnosis and hospitalization

Methods

Information was compiled using electronic medical records. Patients were admitted to Heart Hospital in Qatar, a 116-bed tertiary cardiology center, and were discharged on either atorvastatin (40 mg or 80 mg per oral once daily) or rosuvastatin (20 mg or 40 mg per oral once daily). 

Duration

Admitted between January 1, 2017 to December 31, 2018

Follow-up: 1 year post-discharge after index event

Outcome Measures

Primary: composite endpoint of cardiovascular disease- (CVD) associated death, non-fatal ACS, and non-fatal stroke within 1 month and within 12 months of discharge

Secondary: all-cause mortality, CV-related mortality, fatal or non-fatal stroke, fatal or nonfatal ACS, coronary revascularization, stent thrombosis, stent restenosis within 1 month and 12 months postdischarge, and lowering low-density lipoprotein cholesterol (LDL-C) by ≥ 50% from baseline or LDL-C < 70 mg/dL

Safety: myopathy attributed to statin use or warranted stopping statin therapy or reducing its dose, rhabdomyolysis with a documented rise in creatine kinase by at least 5 times the ULN, elevation of ALT or AST by more than 3 times ULN, any adverse drug event requiring the discontinuation of statin therapy

Baseline Characteristics

Rosuvastatin (n= 627)

Atorvastatin (n= 626)

p-value

Age, years

Male

Weight, kg

Median LDL, mg/dL

Median total cholesterol, mg/dL

Median HDL, md/dL

114

178

35

114

182

35

0.708

0.022

0.132

ALT, U/L

AST, U/L

28

29

29

28

0.927

0.287

High intensity statin dose

20 mg

40 mg

80 mg

619 (98.7%)

8 (1.3%)

-

-

475 (75.9%)

151 (24.1%)

-

-

-

HDL, high-density lipoprotein

Results

Endpoint

Rosuvastatin (n= 627)

Atorvastatin (n= 626)

Adjusted hazard ratio (95% confidence interval)

p-Value

Primary composite endpoint

1 month

12 months

8 (1.3%)

30 (4.8%) 

6 (1.0%)

22 (3.5%)

1.64 (0.55–4.94)

1.48 (0.82–2.67) 

0.379

0.199 

There was no significant difference between groups in any secondary endpoint at 1 month or 12 months.

Adverse Events

Myopathy occurred in 0.5% of patients in the rosuvastatin group and 0.8% in the atorvastatin group. The increase of ALT to > 3 times the ULN was 0.2% in the rosuvastatin group and 0.8% in the atorvastatin group. An increase of AST to >3 times the ULN occurred in 0.3% in the rosuvastatin group and 0.5% in the atorvastatin group. One patient discontinued rosuvastatin due to adverse events, while atorvastatin was discontinued in 3 patients due to adverse events. No rhabdomyolysis was reported in either group. 

Study Author Conclusions

This study suggests that the use of high-intensity rosuvastatin, mainly 20 mg, in secondary prevention post-ACS has a comparable effectiveness and safety to high-intensity atorvastatin over a one-year follow-up period, which may provide a clinician with evidence-based reassurance and more flexibility in the selection of a high-intensity statin therapy.

InpharmD Researcher Critique

A very limited number of patients included in this study were given rosuvastatin 40 mg (n= 8, 1.3%). While the study was conducted in Qatar, the facility was one of the country's main cardiovascular tertiary care centers, with a medical records system integrated within all its major centers.