| Lipid-Lowering Data |
Along with diet, LIPITOR can significantly lower both LDL-C and TG
*Mean change from baseline. LDL-C and TG data are pooled average results from 2 multicenter, placebo-controlled, dose-response studies in patients with primary hypercholesterolemia.
LIPITOR demonstrated powerful LDL-C reductions in high-risk patients with CHD or type 2 diabetes and ≥1 risk factor
Patients with CHD
The TNT trial (N=10,001) evaluated the effect of LIPITOR 80 mg‡ compared with LIPITOR 10 mg on major CV events§ (primary end point) in patients with CHD. Patients randomized to LIPITOR 80 mg‡ (n=4995) experienced the following mean LDL-C reductions after 3 months1,2:
Patients with type 2 diabetes and ≥1 risk factor
The CARDS trial (N=2838) evaluated the effect of LIPITOR 10 mg compared with placebo on major CV events¶ (primary end point) in patients with type 2 diabetes and ≥1 risk factor. Patients randomized to LIPITOR 10 mg (n=1428) experienced the following mean LDL-C reductions after 6 months3:
Patients with type 2 diabetes and CKD
A post hoc subgroup analysis of CARDS evaluated the effect of LIPITOR 10 mg compared with placebo in patients with type 2 diabetes and ≥1 risk factor who also had CKD.4 In this subgroup analysis, patients randomized to LIPITOR 10 mg (n=482) experienced the following mean LDL-C reductions at 3 months2:
As seen in CURVES
LIPITOR reduced LDL-C by >50% with a 40-mg starting dose.5†
Simvastatin, pravastatin, and lovastatin did not provide a mean 50% LDL-C reduction with a starting dose in multiple clinical trials.5-11
As seen in a trial sponsored by AstraZeneca
In this AstraZeneca study, mean LDL-C reductions were comparable for LIPITOR and Crestor across the approved dose ranges, with differences between 3% and 4%. There was no statistical evaluation of the difference in TG reductions across the approved dose ranges of LIPITOR and Crestor. Therefore, statistical superiority cannot be concluded.12
Additionally, according to product labeling, LIPITOR is proven to raise HDL-C 5% to 9%.‡‡
While important, lipids are one part of the story.
- LDL-C reductions are a surrogate measure of efficacy
- AHA/ACC and ADA guidelines recommend making evidence-based treatment decisions13,14
To see LIPITOR CV outcomes evidence click here
To access a library of clinical study abstracts and reprints, click here
†LIPITOR 40 mg may be a starting dose for patients who require an LDL-C reduction of >45%.
‡LIPITOR 80 mg is not a starting dose.
§In TNT, major CV events were defined as time to first occurrence of death from CHD, nonfatal
non-procedure-related MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.1
llMean LDL-C at screening (after washout for patients on lipid-lowering therapy) in the LIPITOR 80 mg arm.
¶In CARDS, major CV events were defined as time to first occurrence of MI, acute CHD death, unstable angina,
resuscitated cardiac arrest, coronary revascularization, or stroke.3
#Based on a calculation of 3.04 mmoL/L divided by 0.02586.
**Based on a calculation of 1.75 mmoL/L divided by 0.02586.
††TG reductions seen with Crestor were not dose dependent: 23%, 22%, 18%, and 26% at the 5-mg, 10-mg,
20-mg, and 40-mg doses, respectively.12
‡‡HDL-C levels with LIPITOR are not dose dependent: 6%, 9%, 6%, and 5% at the 10-mg, 20-mg, 40-mg, and
80-mg doses, respectively.
RRR=relative risk reduction.
Crestor (rosuvastatin calcium) is a registered trademark of the AstraZeneca group of companies.
LIPITOR Important Safety Information and Indications
Please scroll to see the Indications below.
Important Safety Information
LIPITOR is contraindicated in patients with active liver disease or unexplained persistent elevations of hepatic transaminases; in women who are or may become pregnant or who are nursing; in patients with hypersensitivity to any component of this medication.
Rare cases of rhabdomyolysis have been reported with LIPITOR and other statins. Tell patients to promptly report muscle pain, tenderness, or weakness. Predisposing factors include advanced age (≥65), uncontrolled hypothyroidism, and renal impairment. Patients with a history of renal impairment merit closer monitoring. In cases of myopathy or rhabdomyolysis, therapy should be temporarily withheld or discontinued.
The concomitant use of higher doses of LIPITOR with certain drugs such as cyclosporine and strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, and HIV protease inhibitors) increases the risk of myopathy/rhabdomyolysis. Lower doses of LIPITOR should be considered. Physicians should carefully monitor patients for signs or symptoms of myopathy early during therapy and when titrating the dose of either drug.
It is recommended that liver function tests be performed prior to and 12 weeks following both the initiation of therapy and any elevation of dose, and periodically thereafter. If ALT or AST values >3 x ULN persist, dose reduction or withdrawal is recommended.
In a post hoc analysis of the SPARCL study in patients without CHD who had a stroke or TIA within the preceding 6 months, a higher incidence of hemorrhagic stroke was seen in the LIPITOR 80-mg group compared with placebo (2.3% vs 1.4%). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the LIPITOR group.
The most commonly reported adverse reactions with LIPITOR in placebo-controlled trials were: nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection.
Indications
LIPITOR is indicated as an adjunct to diet to reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adult patients with multiple risk factors but without clinically evident coronary heart disease (CHD); to reduce the risk of MI and stroke in patients with type 2 diabetes and without clinically evident CHD, but with multiple risk factors; to reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adult patients with clinically evident CHD.
LIPITOR, as an adjunct to diet, is also indicated to reduce elevated total-C, LDL-C, apo B, and TG levels; and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.
§§LIPITOR $4 Co-Pay Card Terms & Conditions
By using the LIPITOR $4 Co-Pay Card (the "Card"), you acknowledge that you currently meet the eligibility criteria and will comply with the terms and conditions described below:
This Card is not valid for prescriptions that are eligible to be reimbursed, in whole or in part, by Medicaid, Medicare, or other federal or state healthcare programs (including any state prescription drug assistance programs and the Government Health Insurance Plan available in Puerto Rico [formerly known as "La Reforma de Salud"]). The Card is not valid for prescriptions that are eligible to be reimbursed by private insurance plans or other health or pharmacy benefit programs which reimburse you for the entire cost of your prescription drugs. To qualify for this offer, your out-of-pocket expense must be greater than $4 per prescription. If your out-of-pocket expenses for a 1-month supply (30 tablets) are $54 or less, you will pay $4 for a 1-month supply. If your out-of-pocket expenses for a 1-month supply (30 tablets) exceed $54, you qualify for up to $50 in savings for a 1-month supply. In either case, you can only qualify for up to $600 of savings per calendar year. After a maximum of $600, you will pay usual monthly out-of-pocket costs. You must deduct the value received under this program from any reimbursement request submitted to your insurance plan, either directly by you or on your behalf. The Card is not valid for Massachusetts residents whose prescriptions are covered in whole or in part by third-party insurance, or where otherwise prohibited by law. This Card cannot be combined with any other rebate/coupon, free trial, or similar offer for the specified prescription. The Card will be accepted only at participating pharmacies. This Card is not health insurance. Offer good only in the US and Puerto Rico. The Card is limited to 1 per person during this offering period and is not transferable. Offer limited to 1 use per month. Pfizer reserves the right to rescind, revoke or amend the program without notice at any time. Card and Program expire 12/31/2012. No membership fees.
For reimbursement when using a non-participating pharmacy/mail order: Pay for LIPITOR prescription and mail copy of original pharmacy receipt (cash register receipt NOT valid) with product name, date, and amount circled to: LIPITOR Co-Pay Card, 6501 Weston Parkway, Suite 370, Cary, NC 27513. Be sure to include a copy of the front of your Co-Pay Card, your name, and mailing address.
For healthcare professional customer service, call 1-800-505-4426 Monday through Friday, 8:30 AM to 5:30 PM EST or visit www.LipitorHCP.com. Pfizer Inc., 235 East 42nd Street, New York, NY 10017.
Please see full prescribing and patient information
Study Descriptions
TNT (N=10,001) assessed the efficacy and safety of lowering LDL-C <100 mg/dL in CHD patients who achieved a mean LDL-C target level of <130 mg/dL after an 8-week, open-label, run-in period with LIPITOR 10 mg and were then randomized to receive either LIPITOR 80 mg or LIPITOR 10 mg. Eligible patients with CHD were defined as having 1 or more of the following: previous MI, previous or current angina with objective evidence of atherosclerotic CHD, and a history of coronary revascularization. The primary end point was time to first occurrence of a major CV event, defined as fatal CHD, nonfatal non-procedure-related MI, resuscitated cardiac arrest, or fatal or nonfatal stroke.1
CARDS (N=2838) assessed the effect of LIPITOR 10 mg vs placebo in non-CHD patients with type 2 diabetes, elevated cholesterol (LDL-C ≤160 mg/dL, TG ≤600 mg/dL), and ≥1 of the following risk factors: retinopathy, albuminuria, hypertension, or current smoking. The primary end point was time to first occurrence of a major CV event, defined as acute CHD events (ie, MI including silent MI, unstable angina, acute fatal CHD, resuscitated cardiac arrest), coronary revascularization, or stroke.3
A post hoc subgroup analysis of CARDS assessed the effect of LIPITOR 10 mg vs placebo in patients with type 2 diabetes and CKD (n=970). The primary end point evaluated was the same as in the overall study: the first occurrence of a major CV event, defined as acute CHD events (ie, MI including silent MI, unstable angina, acute fatal CHD, resuscitated cardiac arrest), coronary revascularization, or stroke. Patients with eGFR <60 mL/min/1.73 m2, identified at baseline using the Modification of Diet in Renal Disease (MDRD) equation, were classified as having CKD. Patients with CKD had a moderate decrease in kidney function (ie, stage 3 kidney disease as defined by the KDOQI) because only 1 person had an eGFR less than 30 mL/min/1.73 m2 at baseline.4
CURVES (N=534) was an 8-week, randomized, open-label, parallel-group study that compared milligram-milligram doses of LIPITOR with simvastatin, pravastatin, lovastatin, and fluvastatin in patients with LDL-C ≥160 mg/dL and TG ≤400 mg/dL. Baseline LDL-C values were similar and patient demographics evenly distributed across treatment groups. Patients were randomized to LIPITOR 10 mg (n=73), 20 mg (n=51), 40 mg (n=61), or 80 mg (n=10); simvastatin 10 mg (n=70), 20 mg (n=49), or 40 mg (n=61); pravastatin 10 mg (n=14), 20 mg (n=41), or 40 mg (n=25); or lovastatin 20 mg (n=16), 40 mg (n=16), or 80 mg (n=11). LIPITOR 10 mg, 20 mg, and 40 mg produced greater reductions in LDL-C (38%, 46%, and 51%, respectively; P≤.01) compared with equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. LIPITOR 10 mg produced LDL-C reductions comparable with or greater than simvastatin 10 mg, 20 mg, and 40 mg (28%, 35%, and 41%, respectively); pravastatin 10 mg, 20 mg, and 40 mg; lovastatin 20 mg and 40 mg; and fluvastatin 20 mg and 40 mg.5
STELLAR (N=2431) was a 6-week, randomized, parallel-group, open-label trial comparing the efficacy of Crestor with LIPITOR, simvastatin, and pravastatin in patients with LDL-C ≥160 mg/dL to <250 mg/dL and TG <400 mg/dL. Patients were randomized to Crestor 10 mg, 20 mg, 40 mg, or 80 mg; LIPITOR 10 mg, 20 mg, 40 mg, or 80 mg; simvastatin 10 mg, 20 mg, 40 mg, or 80 mg; or pravastatin 10 mg, 20 mg, or 40 mg. This study discusses dosages outside of the approved dose range in that it studied Crestor across a dose range of 10 mg to 80 mg and Crestor 80 mg is not currently an FDA-approved dose. Mean differences between the LDL-C dose-response slopes of Crestor 10 mg to 80 mg vs LIPITOR 10 mg to 80 mg and pravastatin 10 mg to 40 mg were significant (both P<.001). The log-dose slopes of Crestor and simvastatin were not parallel, but equivalent doses were significantly different. Simvastatin LDL-C reductions were 28% at 10 mg, 35% at 20 mg, 39% at 40 mg, and 46% at 80 mg.9
Schneck et al conducted a 6-week double-blind trial comparing the efficacy of LIPITOR with Crestor in 374 patients with LDL-C ≥160 mg/dL to <250 mg/dL and TG <400 mg/dL, but without arterial disease, within 3 months of entry. Patients were randomized to fixed doses of Crestor 5 mg, 10 mg, 20 mg, 40 mg, or 80 mg; or LIPITOR 10 mg, 20 mg, 40 mg, or 80 mg. The primary end point was the percentage change from baseline in LDL-C at week 6 and showed both treatments resulted in dose-dependent reductions in LDL-C. A secondary end point was the percentage change from baseline in TG reductions at week 6. The difference between the linear regression lines for LDL-C lowering, which included assessment up to LIPITOR 80 mg and Crestor 80 mg, demonstrated a mean 8.4% greater reduction in LDL-C with Crestor at any given milligram-equivalent dose compared with LIPITOR (P<.001). Because Crestor 80 mg is not currently an FDA-approved dose, the LDL-C and TG-lowering results seen with this dose are not included.12
References: 1. LaRosa JC, Grundy SM, Waters DD, et al; for Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435. 2. Data on file. Pfizer Inc, New York, NY. 3. Colhoun HM, Betteridge DJ, Durrington PN, et al; for CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685-696. 4. Colhoun HM, Betteridge DJ, Durrington PN, et al; for CARDS Investigators. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis. 2009;54(5):810-819. doi:10.1053j.ajkd. 2009.03.022. 5. Jones P, Kafonek S, Laurora I, Hunninghake D; for CURVES Investigators. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81(5):582-587. 6. Zocor [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 1998. 7. Pravachol [package insert]. Princeton, NJ: Bristol-Myers Squibb Co; 2007. 8. Mevacor [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2007. 9. Jones PH, Davidson MH, Stein EA, et al; for STELLAR Study Group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol. 2003;92(2):152-160.
10. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003;326(7404):1-7. doi:10.1136/bmj.326.7404.1423. 11. Schaefer EJ, McNamara JR, Tayler T, et al. Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Am J Cardiol. 2004;93(1):31-39. 12. Schneck DW, Knopp RH, Ballantyne CM, McPherson R, Chitra RR, Simonson SG. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am J Cardiol. 2003;91(1):33-41. 13. Smith SC Jr, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006;47(10):2130-2139. 14. American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care. 2011;34(suppl 1):S11-S61.
