The Efficacy Profile of LIPITOR

The Efficacy Profile of LIPITOR®

LIPITOR®Has Greater LDL-C Reductions in Every Dose: Head-to-Head Study1

Head-to-Head Study1

"01- LDL-C Reduction Head-to-Head Study 02- Cardiovascular Outcome Trials 03- The Efficacy Profile of LIPITOR 04- Powerful LDL-C Reductions Comparable with Rosuvastatin 05- More Cardiovascular Outcomes Data than Rosuvastatin"

LIPITOR® vs Ezetimibe/Simvastatin

LIPITOR® Has Established Evidence of CV Event Reduction Across a Wider Range of Patients Compared with Ezetimibe/Simvastatin*†ǂ2-8

CV Outcome Trials

 

LIPITOR® vs. Rosuvastatin

LIPITOR® Provides Powerful LDL-C Reductions Comparable with Rosuvastatin10

LIPITOR® Has More CV Outcomes Data than Rosuvastatin2-7,10-15

*Ezetimibe/Simvastatin dose range is 10/10 mg/day to 10/80 mg/day. The risk of myopathy is greater in patients on ezetimibe/simvastatin 10/80 mg, therefore this dose should only be used in patients with severe hypercholesterolemia and at high risk for cardiovascular complications who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks.9

†Based on target patient populations in each outcomes trial.

ǂLIPITOR® (atorvastatin calcium) is not currently approved for patients with established/documented CVD in Gulf countries (UAE, Bahrain, Oman, Qatar and Kuwait).

ACS: acute coronary syndrome; CV: cardiovascular; CHD; coronary heart disease; CKD: chronic kidney disease; LDL-C: low-density lipoprotein cholesterol; TIA:  transient ischemic attack.

 

References:

  1. Jones P, Kafonek S, Laurora I, Hunninghake D. 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.
  2. Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-1158.
  3. Colhoun HM, Betteridge DJ, Durrington PN, et al. 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. Wanner C, Krane V, März W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238-248.
  5. Knopp RH, d'Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non–insulin–dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29(7):1478-1485.
  6. Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359(13):1343-1356.
  7. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181-2192.
  8. Braunwald E, Califf R, Cannon C, et al. IMProved Reduction of Outcomes: Vytorin Efficacy International Trial. Presented at the American Heart Association Scientific Sessions, November 2014.
  9. INEGY® (ezetimbe and simvastatin) tablets [ Summary of Product Characteristics]. United Arab Emirates; Merck Sharp & Dohme Corp. Updated 2016.
  10. National Institute for Health and Care Excellence (NICE). Cardiovascular disease: risk assessment and reduction, including lipid modification. Available at https://www.nice.org.uk/guidance/cg181/resources/cardiovascular-disease-.... Published July 2014. Updated September 2016. Accessed 26 April 2022.
  11. Fellström BC, Jardine AG, Schmieder RE, et al; for AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395-1407.
  12. Kjekshus J, Apetrei E, Barrios V, et al; CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357(22):2248-2261.
  13. Tavazzi L, Maggioni AP, Marchioli R, et al. GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231-1239.
  14. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.
  15. Yusuf S, Bosch J, Dagenais G, et al; HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease [published online ahead of print April 2, 2016]. N Engl J Med. doi:10.1056/NEJMoa1600176.

LIPI-2022-0503

The Safety Profile of LIPITOR

LIPITOR® Has an Established Safety Profile Across the Dose Range1,2

Established Safety Profile Across the Dose Range 

Adapted from LIPITOR® (atorvastatin calcium) Summary of Product Characteristics. January 2019 for UAE, Qatar, Iraq, Bahrain, Oman and June 2016 for Kuwait.1; Newman C et al., Am J Cardiol, 2006;2 CRESTOR® Summary of Product Characteristics 2014;3 ZOCOR® Package Leaflet 2012;4 INEGY® Summary of Product Characteristics 2016.5

 Summary of Product Characteristics

Diabetes Patient Safety
LIPITOR® Demonstrates a Proven Safety Profile Across the Dose Range in Patients with Diabetes6

CARDS Safety Results in Patients with Type 2 Diabetes6

CARDS Safety Results in Patients with Type 2 Diabetes

  • In CARDS, the frequency of adverse events or serious adverse events did not differ between LIPITOR® 10 mg and placebo.6

CARDS study design:6

  • Double-blind, prospective study in which 2838 patients aged 40 to 75 years were randomized to LIPITOR® 10 mg (n=1428) or placebo (n=1410)
  • Patients had type 2 diabetes, no documented history of CVD, LDL-C ≤160 mg/dL, TG ≤600 mg/dL, and ≥1 of the following: hypertension, retinopathy, albuminuria, or current smoking
  • The primary endpoint was time to first occurrence of acute CHD events, coronary revascularization, or stroke
  • Median duration of follow-up was 4.0 years (IQR 3.0-4.7) in the atorvastatin group; the CARDS trial was terminated at 3.9 years to 2 years earlier than planned—due to highly significant benefits of atorvastatin

PLANET I Safety Results in Patients with Diabetes and CKD7

LIPITOR® significantly reduced UPCR at week 52 vs baseline7

Lipitor Img 1

*Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): Randomized, double-blind, parallel-group trial at 147 research centers including 353 patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria (urine protein: creatinine ratio [UPCR] 500–5000 mg/g) and taking stable ACEIs, ARBs, or both. Patients were randomized to atorvastatin 80 mg (n=102), rosuvastatin 10 mg (n=107), or rosuvastatin 40 mg (n=116) for 52 weeks. The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group.7

LIPITOR® maintained eGFR at week 52 vs. baseline7

 

Lipitor Img 2

PLANET I study design:*7

  • Randomized, double-blind, parallel-group trial at 147 research centers
  • Included 353 patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria (UPCR 500-5000 mg/g) and taking stable ACEIs, ARBs, or both
  • Patients were randomized to atorvastatin 80 mg (n=102), rosuvastatin 10 mg (n=107), or rosuvastatin 40 mg (n=116) for 52 weeks
  • The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group

CKD Patient Safety

LIPITOR® Has Demonstrated Safety in Patients With CKD, and Showed No Adverse Effect on eGFR Across the Dose Range8-10

  • No dose adjustment required in patients with renal impairment1
  • In PLANET I (n=353) in patients with moderate proteinuria, hypercholesterolemia, and diabetes, LIPITOR® 80 mg had no adverse effect on proteinuria or estimated glomerular filtration rate (eGFR) at 52 weeks compared to baseline7*
  • According to 2019 ESC/EAS dyslipidemia guidelines, ‘the use of statins or statin/ezetimibe combination is indicated in patients with non-dialysis-dependent stage 3-5 CKD10

LIPITOR®  80 mg reduced proteinuria and maintained eGFR in patients with CKD7

LIPITOR® significantly reduced UPCR at week 52 vs baseline7

 reduced proteinuria and maintained eGFR in patients with CKD  reduced proteinuria and maintained eGFR in patients with CKD 

†Prospective evaluation of proteinuria and renal function in nondiabetic patients with progressive renal disease (PLANET II): Randomized, double-blind, parallel-group trial at 114 research centers including 237 patients without diabetes, aged ≥18 years with proteinuria (urine protein: creatinine ratio [UPCR] 500-5000 mg/g) and taking stable ACEIs, ARBs, or both. Patients were randomized to atorvastatin 80 mg (n=75), rosuvastatin 10 mg (n=65), or rosuvastatin 40mg (n=80) for 52 weeks. The primary endpoint was change from baseline to week 52 or mean UPCR in each treatment group.11

LIPITOR® maintained eGFR at week 52 vs baseline7

 

 reduced proteinuria and maintained eGFR in patients with CKD  

 reduced proteinuria and maintained eGFR in patients with CKD

PLANET I study design:*7

  • Randomized, double-blind, parallel-group trial at 147 research centers
  • Included 353 patients with type 1 or type 2 diabetes aged 18 years or older with proteinuria (UPCR 500–5000 mg/g) and taking stable ACEIs, ARBs or both
  • Patients were randomized to atorvastatin 80 mg (n=102), rosuvastatin 10 mg (n=107) or rosuvastatin 40 mg (n=116) for 52 weeks
  • The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group

PLANET II study design:11

  • Randomized, double-blind, parallel-group trial at 114 research centers
  • Included 237 patients without diabetes, aged ≥18 years with proteinuria (UPCR 500-5000 mg/g) and taking stable ACEIs, ARBs or both
  • Patients were randomized to atorvastatin 80 mg (n=75), rosuvastatin 10 mg (n=65) or rosuvastatin 40 mg (n=80) for 52 weeks
  • The primary endpoint was change from baseline to week 52 or mean UPCR in each treatment group

Asian Patient Safety

A Retrospective Analysis Assessed the Safety of LIPITOR® in Asian Patients in 58 Randomized Trials12

Asian Patient Safety

Pharmacokinetic data (AUC and Cmax) are similar between Asian and Caucasian patients13

Heritage

LIPITOR® Has the Experience You Can Trust6,8,14-23

LIPITOR Has the Experience You Can Trust

*Proteinuria at baseline defined as urinary protein/creatinine excretion ratio of 500 to 5000 mg/g.7

ACEI: angiotensin converting enzymes inhibitor; ALT: alanine aminotransferase; ARB: angiotensin II receptor blocker; AST: aspartate aminotransferase; CARDS: Collaborative AtoRvastatin Diabetes Study; CHD: coronary heart disease; CK: creatine kinase; CKD: chronic kidney disease; CV: cardiovascular; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; EAS: European Atherosclerosis Society; ESC: European Society of Cardiology; HDL-C: high-density lipoprotein cholesterol; IQR: interquartile range; LDL-C: low-density lipoprotein cholesterol; LOCF: last observation carried forward; MI: myocardial infarction; PLANET I: Renal Effects of Atorvastatin and Rosuvastatin in Patients with Diabetes who have Progressive Renal Disease; PLANET II: Prospective Evaluation of Proteinuria and Renal Function in Nondiabetic Patients With Progressive Renal Disease; RRR: relative risk reduction; TC: total cholesterol; TG: triglycerides; ULN: upper limit of normal; UPCR: urine protein to creatinine ratio.

References:

  1. LIPITOR® (atorvastatin calcium) Summary of Product Characteristics. January 2019 for UAE, Qatar, Iraq, Bahrain, Oman and June 2016 for Kuwait.
  2. Newman C, Tsai J, Szarek M, et al; Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients. Am J Cardiol. 2006;97(1):61-67.
  3. CRESTOR® (rosuvastatin calcium) Summary of Product Characteristics.2014.
  4. ZOCOR® (simvastatin) Package Leaflet. 2012.
  5. INEGY® (ezetimibe and simvastatin) Summary of Product Characteristics.2016.
  6. Colhoun HM, Betteridge DJ, Durrington PN, et al; 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.
  7. de Zeeuw D, Anzalone DA, Cain VA, et al. Renal effects of atorvastatin and rosuvastatin in patients w3th diabetes who have progressive renal disease (PLANET I): a randomised clinical trial. Lancet Diabetes Endocrinol. 2015;3(3):181-190.
  8. LaRosa JC, Grundy SM, Waters DD, et al; 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.
  9. Koren MJ, Davidson MH, Wilson DJ, et al. Focused atorvastatin therapy in managed-care patients with coronary heart disease and CKD. Am J Kidney Dis. 2009;53(5):741-750.
  10. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2019;00:1-78.
  11. Prospective Evaluation of Proteinuria and Renal Function in Non-diabetic Patients With Progressive Renal Disease (PLANET II).Clinical trials.gov. Available at https://clinicaltrials.gov/ct2/show/study/NCT00296400#wrapper. Accessed 26 April 2022.
  12. Chan JC, Kong AP, Bao W, Fayyad R, Laskey R. Safety of atorvastatin in Asian patients within clinical trials. Cardiovasc Ther. 2016;34(6):431-440.
  13. Gandelman K, Fung GL, Messig M, Laskey R. Systemic exposure to atorvastatin between Asian and Caucasian subjects: a combined analysis of 22 studies. Am J Ther. 2012;19(3):164-173.
  14. Data on file. Reference available upon request.
  15. IMS List of Countries. Reference available upon request.
  16. IMS Patient Years Experience. Reference available upon request.
  17. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495-1504.
  18. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285(13):1711-1718. 
  19. Koren MJ, Hunninghake DB. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the ALLIANCE study. J Am Coll Cardiol. 2004;44(9):1772-1779.
  20. Pederson TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437-2445.
  21. Wanner C, Krane V, März W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238-248.
  22. Knopp RH, d'Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non–insulin–dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29(7):1478-1485.
  23. Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-1158.

LIPI-2022-0503

Treating Patients With Hypertension and Multiple Risk Factors

Treating Patients with Hypertension and Multiple Risk Factors

Hypertension + ≥3 Additional Risk Factors

In the ASCOT-LLA trial in patients with hypertension and ≥3 additional risk factors, LIPITOR® 10 mg reduced the risk of nonfatal MI and fatal CHD by 36% compared with placebo1

 

reduced the risk of nonfatal MI and fatal CHD by 36%  

  • LIPITOR® 10 mg reduced mean LDL-C from 133 mg/dL (3.44 mmol/L) to 90 mg/dL (2.32 mmol/L) over the course of the study1

Hypertension + ≥2 Additional Risk Factors

In an ASCOT-LLA post hoc subgroup analysis in patients with hypertension, diabetes, and ≥2 additional risk factors, LIPITOR® 10 mg reduced the risk of total CV events and procedures by 23% compared with placebo2

        

Adapted from Sever PS et al. Diabetes Care.2005.

ASCOT-LLA Study design1,2

  • Double-blind, placebo-controlled study including 10,305 hypertensive patients treated with antihypertensive therapy and without a previous MI with TC ≤250 mg/dL (6.5 mmol/L)
  • Patients also had ≥3 additional CV risk factors
  • Randomized to LIPITOR® 10 mg (n=5168) or placebo (n=5137)
  • Trial was terminated early (after a median follow-up of 3.3 years) on the recommendation of the data safety monitoring board, due to the significant early difference between groups in the primary endpoint
  • Analysis includes the 2532 patients with diabetes randomized to LIPITOR® (n=1258) or placebo (n=1274)

ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm; CHD: coronary heart disease; CV: cardiovascular;  MI: myocardial infarction; RRR: relative risk reduction; TC: total cholesterol.

References:

  1. Sever PS, Dahlöf B, Poulter NR, et al; ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-1158.
  2. Sever PS, Poulter NR, Dahlöf B, et al; ASCOT Investigators. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes:        Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA). Diabetes Care. 2005;28(5):1151-1157.

LIPI-2022-0503

Treating Patients With Diabetes

Treating Patients with Diabetes

LIPITOR® Provides Significant CV Risk Reduction in Patients with Diabetes1

Hypertension + Diabetes + ≥2 Additional Risk Factors

In an ASCOT-LLA post hoc subgroup analysis in patients with hypertension, diabetes, and ≥2 additional risk factors, LIPITOR® 10 mg reduced the risk of total CV events and procedures by 23% compared with placebo2

Lipitor reduced the risk of total CV events and procedures by 23%

Adapted from Sever PS et al. Diabetes Care. 2005.

ASCOT-LLA Study Design2

  • Double-blind, placebo-controlled study including 10,305 hypertensive patients treated with antihypertensive therapy and without a previous MI with TC ≤250 mg/dL (6.5 mmol/L)
  • Patients also had ≥3 additional CV risk factors
  • Randomized to LIPITOR® 10 mg (n=5168) or placebo (n=5137)
  • Trial was terminated early (after a median follow-up of 3.3 years) on the recommendation of the data safety monitoring board, due to the significant early difference between groups in the primary endpoint.
  • Analysis includes the 2532 patients with diabetes randomized to LIPITOR® (n=1258) or placebo (n=1274)

Diabetes + ≥1 Additional Risk Factor

In the CARDS trial in patients with type 2 diabetes and ≥1 other CHD risk factor, LIPITOR® 10 mg reduced the risk of major CV events by 37% compared with placebo1

ASCOT-LLA Study Design

*Major CV events: MI (including silent MI), unstable angina, acute CHD death, resuscitated cardiac arrest, coronary revascularization, and stroke.4

Lipitor reduced the risk of MI by 42%

  • LIPITOR® 10 mg also reduced the risk of MI by 42% (P=0.007)3

In the CARDS trial in patients with type 2 diabetes and ≥1 risk factor, LIPITOR® 10 mg reduced the risk of stroke by nearly half compared with placebo4

Lipitor reduced the risk of stroke by nearly half

*Major CV events: MI (including silent MI), unstable angina, acute CHD death, resuscitated cardiac arrest, coronary revascularization, and stroke.4

The lowest mean LDL-C level reached with LIPITOR

  • The lowest mean LDL-C level reached with LIPITOR® in this study was 68 mg/dL (1.8 mmol/L)1

CARDS Study Design1,4,5

  • Double-blind, prospective study in which 2838 patients aged 40 to 75 years were randomized to LIPITOR® 10 mg (n=1428) or placebo (n=1410)
  • Patients had type 2 diabetes, no documented history of CVD, LDL-C ≤160 mg/dL, TG ≤600 mg/dL, and ≥1 of the following: hypertension, retinopathy, albuminuria, or current smoking
  • The primary endpoint was time to first occurrence of acute CHD events, coronary revascularization, or stroke
  • Median duration of follow-up was 4.0 years (IQR 3.0-4.7) in the atorvastatin group; the CARDS trial was terminated at 3.9 years—2 years earlier than planned—due to highly significant benefits of atorvastatin

Diabetes + CKD,

In the CARDS post hoc subgroup analysis in high-risk patients with type 2 diabetes and CKD*, LIPITOR® 10 mg significantly reduced the risk of stroke compared with placebo5

LIPITOR reduced mean LDL-C

  • In the CARDS post hoc subgroup analysis, LIPITOR® 10 mg (n=482) reduced mean LDL-C from baseline 120 mg/dL to 71 mg/dL5

CARDS Study design1,4,5

  • Double-blind, prospective study in which 2838 patients aged 40 to 75 years were randomized to LIPITOR® 10 mg (n=1428) or placebo (n=1410)
  • Patients had type 2 diabetes, no documented history of CVD, LDL-C ≤160 mg/dL, TG ≤600 mg/dL, and ≥1 of the following: hypertension, retinopathy, albuminuria, or current smoking
  • The primary endpoint was time to first occurrence of acute CHD events, coronary revascularization, or stroke
  • Median duration of follow-up was 4.0 years (IQR 3.0-4.7) in the atorvastatin group; the CARDS trial was terminated at 3.9 years—2 years earlier than planned—due to highly significant benefits of atorvastatin

ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm; CARDS: Collaborative AtoRvastatin Diabetes Study; CHD: coronary heart disease; CV: cardiovascular; CVD: cardiovascular disease; CKD: chronic kidney disease; HDL-C: high-density lipoprotein cholesterol; IQR: interquartile range; LDL-C: low-density lipoprotein cholesterol; MI: myocardial infarction; RRR: relative risk reduction; TC: total cholesterol; TG: triglycerides.

References:

  1. Colhoun HM, Betteridge DJ, Durrington PN, et al; 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.
  2. Sever PS, Poulter NR, Dahlöf B, et al; ASCOT Investigators. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA). Diabetes Care. 2005;28(5):1151-1157.
  3. LIPITOR® (atorvastatin calcium) Summary of Product Characteristics. January 2019 for UAE, Qatar, Iraq, Bahrain, Oman and June 2016 for Kuwait.
  4. Hitman GA, Colhoun H, Newman C, et al. Stroke prediction and stroke prevention with atorvastatin in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabet Med. 2007;24(12):1313-1321.
  5. Colhoun HM, Betteridge DJ, Durrington PN, et al; 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 Kid Dis. 2009;54(5):810-819.

LIPI-2022-0503

Primary Prevention Of Stroke

Primary Prevention of Stroke

Diabetes + ≥1 Additional Risk Factor
In the CARDS trial in patients with type 2 diabetes and ≥1 risk factor, LIPITOR® 10 mg reduced the risk of stroke by nearly half compared with placebo1

LIPITOR reduced the risk of stroke by nearly half

*Major CV events: MI (including silent MI), unstable angina, acute CHD death, resuscitated cardiac arrest, coronary revascularization, and stroke.1

The lowest mean LDL-C level reached with LIPITOR
  • The lowest mean LDL-C level reached with LIPITOR® in this study was 68 mg/dL (1.8 mmol/L)2

CARDS Study Design1,2

  • Double-blind, prospective study in which 2838 patients aged 40 to 75 years were randomized to LIPITOR® 10 mg (n=1428) or placebo (n=1410)
  • Patients had type 2 diabetes, no documented history of CVD, LDL-C ≤160 mg/dL, TG ≤600 mg/dL, and ≥1 of the following: hypertension, retinopathy, albuminuria, or current smoking
  • The primary endpoint was time to first occurrence of acute CHD events, coronary revascularization, or stroke
  • Median duration of follow-up was 4.0 years (IQR 3.0-4.7) in the atorvastatin group; the CARDS trial was terminated at 3.9 years—2 years earlier than planned—due to highly significant benefits of atorvastatin

Diabetes + CKD

In the CARDS post hoc subgroup analysis in high-risk patients with type 2 diabetes and CKD, LIPITOR® 10 mg significantly reduced the risk of stroke compared with placebo5

significantly reduced the risk of stroke compared with placebo
  • In the CARDS post hoc subgroup analysis, LIPITOR® 10 mg (n=482) reduced mean LDL-C from baseline 120 mg/dL to 71 mg/dL3

CARDS study design1-3

  • Double-blind, prospective study in which 2838 patients aged 40 to 75 years were randomized to LIPITOR® 10 mg (n=1428) or placebo (n=1410)
  • Patients had type 2 diabetes, no documented history of CVD, LDL-C ≤160 mg/dL, TG =600 mg/dL, and ≥1 of the following: hypertension, retinopathy, albuminuria, or current smoking
  • The primary endpoint was time to first occurrence of acute CHD events, coronary revascularization, or stroke
  • Median duration of follow-up was 4.0 years (IQR 3.0-4.7) in the atorvastatin group; the CARDS trial was terminated at 3.9 years—2 years earlier than planned—due to highly significant benefits of atorvastatin

Hypertension + ≥3 Additional Risk Factors

In the ASCOT-LLA trial in patients with hypertension and ≥3 additional risk factors, LIPITOR® 10 mg reduced the risk of fatal and nonfatal stroke by 27% compared with placebo4

ASCOT-LLA study design

ASCOT-LLA study design4

  • Double-blind, placebo-controlled study including 10,305 hypertensive patients treated with antihypertensive therapy and without a previous MI with TC ≤250 mg/dL (6.5 mmol/L)
  • Patients also had ≥3 additional CV risk factors
  • Randomized to LIPITOR® 10 mg (n=5168) or placebo (n=5137)
  • Trial was terminated early (after a median follow-up of 3.3 years) on the recommendation of the data safety monitoring board, due to the significant early difference between groups in the primary endpoint
  • Analysis includes the 2532 patients with diabetes randomized to LIPITOR® (n=1258) or placebo (n=1274)

ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm; CARDS:Collaborative AtoRvastatin Diabetes Study; CHD: coronary heart disease; CV: cardiovascular; CVD: cardiovascular disease; CKD: chronic kidney disease; HDL-C: high-density lipoprotein cholesterol; IQR: interquartile range; LDL-C: low-density lipoprotein cholesterol; MI: myocardial infarction; RRR: relative risk reduction; TC: total cholesterol; TG: triglycerides.


References:

  1. Hitman GA, Colhoun H, Newman C, et al. Stroke prediction and stroke prevention with atorvastatin in the Collaborative Atorvastatin Diabetes Study (CARDS). Diabet Med. 2007;24(12):1313-1321.
  2. Colhoun HM, Betteridge DJ, Durrington PN, et al; 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.
  3. Colhoun HM, Betteridge DJ, Durrington PN, et al; 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 Kid Dis. 2009;54(5):810-819.
  4. Sever PS, Dahlöf B, Poulter NR, et al; ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-1158.
  5. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care 2022;45(Suppl.1):S1–S254.

LIPI-2022-0503

Patient Profile

Patient Profiles

Diabetes
LIPITOR® Provides Significant CV Risk Reduction in Patients with Diabetes1

LIPITOR Provides Significant CV Risk Reduction in Patients with Diabetes

Farah*

Age: 61 years old
Occupation: Seamstress
Family status: Married, 4 children.
Overweight: BMI 29.7

Hypertension for 11 years

  • Treated with amlodipine 5 mg.
  • Current BP: 125/80 mm Hg

Type 2 diabetes for 10 years

  • Fasting plasma glucose: 119 mg/dL
  • HbA1c: 6.8%
  • Taking metformin 500 mg BID

Menopausal

Lipid profile

  • TC: 237 mg/dL (6.1 mmol/L)
  • LDL-C: 132 mg/dL (3.4 mmol/L)
  • TG: 240 mg/dL (2.7 mmol/L)
  • HDL-C: 38 mg/dL (1.0 mmol/L)

  10-year ACC/AHA ASCVD Risk

  • 12.5% calculated risk
Recent guidelines recommend moderate-† to-high-intensity‡ statin therapy to reduce CV risk in patients with diabetes2-5 

Recent guidelines recommend moderate to high-intensity statin therapy

Cardiovascular outcomes in patients with diabetes

Lipitor Safety Profile

*This patient case study is fictional. Medical profile data have been derived for illustrative purposes only.

Moderate-intensity statin is defined as statin therapy that results in approximately 30% to <50% LDL-C reduction.2,3

High-intensity statin is defined as statin therapy that results in ≥50% LDL-C reduction.2,3

Hypertension
LIPITOR® Provides Proven Outcomes for High-Risk Patients with Primary Hypertension6

Proven Outcomes for High-Risk Patients with Primary Hypertension

Addullah*

Age: 55 years old
Occupation: Vendor
Family status: Widowed
Overweight: BMI 25.3

Hypertension for 23 years

  • Mean SBP=151 mm Hg
  • Taking amlodipine 5 mg QD

Lipid Profile

  • TC: 220 mg/dL (5.7 mmol/L)
  • LDL-C: 147 mg/dL (3.8 mmol/L)
  • TG: 160 mg/dL (1.81 mmol/L)
  • HDL-C: 35 mg/dL (0.91 mmol/L)

10-Year ACC/AHA ASCVD Risk

  • 11.2% calculated risk

Guidelines recommend statin therapy for the primary prevention of CVD4,5,7

Guidelines recommend statin therapy for the primary prevention of CVD

*This patient case study is fictional. Medical profile data have been derived for illustrative purposes only.

Hypertension and Multiple Risk Factors
LIPITOR® Provides Significant CV Risk Reduction in Patients with Hypertension and Multiple Risk Factors6

Significant CV Risk Reduction in Patients with Hypertension and Multiple Risk Factors

Maria*

Age: 54 years old
Occupation: Florist
Family status: Married,3 children
Overweight: BMI 29.8

Hypertension for 3 years

  • Treated with 5mg amlodipine per day
  • Current BP: 135/80 mm Hg

Smoker

  • 10 packs/week for 10 years

Menopausal

Lipid profile
  • TC: 246 mg/dL (6.4 mmol/L)
  • LDL-C: 155 mg/dL (4.0 mmol/L)
  • TG: 225 mg/dL (2.5 mmol/L)
  • HDL-C: 46 mg/dL (1.2 mmol/L)

10-Year ACC/AHA ASCVD Risk

  • 10.0% calculated risk

Guidelines recommend moderate- to-high- intensity statin therapy in patients with hypertension and multiple CV risk factors.3-5,7

Guidelines recommend moderate-to-high intensity statin therapy

*This patient case study is fictional. Medical profile data have been derived for illustrative purposes only.
Moderate-intensity statin is defined as statin therapy that results in approximately 30% to <50% LDL-C reduction.3
High-intensity statin is defined as statin therapy that results in ≥50% LDL-C reduction.3

Cardiovascular outcomes in patients with diabetes

 

Lipitor Safety Profile

 

ACC: American College of Cardiology; ADA: American Diabetes Association; AHA: American Heart Association; ASCVD; atherosclerotic cardiovascular disease; BID: twice daily; BP: blood pressure; CV: cardiovascular; CVD: cardiovascular disease; ESC: European Society of Cardiology; ESH: European Society of Hypertension; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; NICE: National Institute for Health and Care Excellence; QD: once daily; SBP: systolic blood pressure; TC: total cholesterol; TG: triglycerides.

References:

  1. Colhoun HM, Betteridge DJ, Durrington PN, et al; CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet. 2004;364(9435):685-696.
  2. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care 2022;45(Suppl.1):S1–S254.
  3. AmettDK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646.
  4. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104.
  5. National Institute for Health and Care Excellence (NICE). Cardiovascular disease: risk assessment and reduction, including lipid modification. Available at: https://www.nice.org.uk/guidance/cg181. Published July 2014. Updated September 2016. Accessed 26 April 2022.
  6. Sever PS, Dahlöf B, Poulter NR, et al; ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-1158.
  7. FLJ Visseren, F Mach, YM Smulders, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC) . Eur Heart J. 2021;42(34):3227-3337.

LIPI-2022-0503

Highlights Of Prescribing Information

These highlights do not include all the information needed to use LIPITOR® safely and effectively. See full Prescribing Information for LIPITOR®.

Dosing
LIPITOR® Dosing Guide1

LIPITOR® is available in 10, 20, 40, and 80 mg tablets.1

LIPITOR Dosing Guide

 

LIPITOR® may be used with bile acid resins.1
The combination of HMG-CoA reductase inhibitors (statins) and fibrates should generally be used with caution.1
Dosage adjustment in patients with renal dysfunction is not necessary.1

See full Prescribing Information for LIPITOR.

Contraindications

Contraindications1

  • Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels exceeding three times the upper limit of normal.
  • Women who are pregnant or may become pregnant.
  • Nursing mothers
  • Hypersensitivity to any component of this medication

Warnings + Precautions

Warnings + Precautions1

Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase when higher doses are used concomitantly with cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, HIV protease inhibitors). Predisposing factors include advanced age (>65), uncontrolled hypothyroidism, and renal impairment. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported. Advise patients to promptly report to their physician any unexplained and/or persistent muscle pain, tenderness, or weakness. LIPITOR® therapy should be discontinued if myopathy is diagnosed or suspected.1 Liver enzyme abnormalities: Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter.1 A higher incidence of hemorrhagic stroke was seen in patients without CHD but with stroke or TIA within the 6 months before therapy in the LIPITOR® 80 mg group versus placebo.1

Undesirable Effects

Undesirable Effects1
The common undesirable effects are nasopharyngitis allergic reaction, hyperglycemia, headache, pharyngolaryngeal pain, epistaxis, constipation, flatulence, dyspepsia, nausea, diarrhea, myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain, liver function test abnormal, blood creatine kinase increased.1

To learn more about how to report SUSPECTED ADVERSE REACTIONS, please review the Report Adverse Events page

Drug Interactions

Drug Interactions1

To learn more about how to report SUSPECTED ADVERSE REACTIONS, please review the Report Adverse Events page

Lipitor Drug Interactions

 

  • Other Lipid-Lowering Medications: Use of LIPITOR® with fibrate products or lipid-modifying doses of niacin increases the risk of adverse skeletal muscle effects. Caution should be used when prescribing with LIPITOR®.1
  • Digoxin: Patients should be monitored appropriately.1
  • Oral Contraceptives: Values for norethindrone and ethinyl estradiol may be increased.1
  • Rifampin should be simultaneously co-administered with LIPITOR®.1

References:

  1. LIPITOR® (atorvastatin calcium) Summary of Product Characteristics. January 2019 for UAE, Qatar, Iraq, Bahrain, Oman and June 2016 for Kuwait.

LIPI-2022-0503

Abbreviated Prescribing Information

Lipitor® (Atorvastatin) Abbreviated Prescribing Information.

Presentation: Lipitor supplied as white, elliptical film-coated tablet containing 10 mg, 20 mg, 40 mg, and 80 mg of atorvastatin as excipient atorvastatin calcium trihydrate in blister packs of 30 and/or 100 film-coated tablets. Indications: Hypercholesterolaemia: Lipitor is indicated as an adjunct to diet for reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides in adults, adolescents and children aged 10 years or older with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (Corresponding to Types IIa and IIb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate. Lipitor is also indicated to reduce total-C and LDL-C in adults with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable. Prevention of cardiovascular disease: Prevention of cardiovascular events in adult patients estimated to have a high risk for a first cardiovascular event as an adjunct to correction of other risk factors. Dosage and Administration: Posology: Patient should be placed on a standard cholesterol-lowering diet before receiving Lipitor and should continue this diet during treatment with Lipitor. Usual starting dose is 10 mg once a day. Adjustment of dose should be made at intervals of 4 weeks or more. The maximum dose is 80 mg once a day. Lipitor is for oral administration. Each daily dose of atorvastatin is given all at once and may be given at any time of day with or without food. Prevention of cardiovascular disease: In the primary prevention trials the dose was 10 mg/day. Higher doses may be necessary in order to attain (LDL-) cholesterol levels according to current guidelines. Renal impairment: No adjustment of dose is required. Hepatic impairment: Should be used with caution in patients with hepatic impairment. Lipitor is contraindicated in patients with active liver disease. Elderly: Efficacy and safety in patients older than 70 using recommended doses are like those seen in the general population. Paediatric population: Paediatric use should only be carried out by physicians experienced in the treatment of paediatric hyperlipidaemia and patients should be re-evaluated on a regular basis to assess progress. For patients with Heterozygous Familial Hypercholesterolemia aged 10 years and above, the recommended starting dose of atorvastatin is 10 mg per day. The dose may be increased to 80 mg daily, according to the response and tolerability. Atorvastatin is not indicated in the treatment of patients below the age of 10 years. Contraindications: Hypersensitivity to the active substance or to any of the excipients, active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal, during pregnancy, while breast-feeding and in women of child-bearing potential not using appropriate contraceptive measures. Special warnings and precautions: Liver effects: LFT should be performed before the initiation of treatment and periodically thereafter. Patients who develop any signs or symptoms suggestive of liver injury should have liver function tests performed. Should an increase in transaminases of greater than 3 times the upper limit of normal (ULN) persist, reduction of dose or withdrawal of Lipitor is recommended. Lipitor should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL): In a post-hoc analysis of stroke subtypes in patients without coronary heart disease (CHD) who had a recent stroke or transient ischemic attack (TIA) there was a higher incidence of haemorrhagic stroke in patients initiated on atorvastatin 80 mg compared to placebo. The increased risk was particularly noted in patients with prior haemorrhagic stroke or lacunar infarct at study entry. Skeletal muscle effects: Atorvastatin may in rare occasions affect the skeletal muscle and cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis, myoglobinaemia and myoglobinuria which may lead to renal failure. Interactions: Risk of rhabdomyolysis is increased when atorvastatin is administered concomitantly with certain medicinal products that may increase the plasma concentration of atorvastatin such as potent inhibitors of CYP3A4 or transport proteins (e.g. ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc). The risk of myopathy may also be increased with the concomitant use of gemfibrozil and other fibric acid derivates, erythromycin, niacin, ezetimibe, or the combination of tipranavir/ritonavir also with the concomitant use of other antivirals for the treatment of hepatitis C (HCV) like (boceprevir, telaprevir, elbasvir/grazoprevir), In cases where co-administration of these medicinal products with atorvastatin cannot be avoided lower starting and maximum doses of atorvastatin should be considered and appropriate clinical monitoring of the patient is recommended. Fertility, Pregnancy and lactation: Women of childbearing potential: Women of child-bearing potential should use appropriate contraceptive measures during treatment. Pregnancy: Lipitor is contraindicated during pregnancy. Breast-feeding: Atorvastatin is contraindicated during breast-feeding. Fertility: In animal studies atorvastatin had no effect on male or female fertility. Effects on ability to drive and use machines: Lipitor has negligible influence on the ability to drive and use machines. Undesirable effects: In the atorvastatin placebo-controlled clinical trial database of 16,066 (8755 Lipitor vs. 7311 placebo) patients treated for a mean period of 53 weeks, 5.2% of patients on atorvastatin discontinued due to adverse reactions compared to 4.0% of the patients on placebo. The common undesirable effects are nasopharyngitis, allergic reaction, hyperglycaemia, headache, pharyngolaryngeal pain, epistaxis, constipation, flatulence, dyspepsia, nausea, diarrhoea, myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain, liver function test abnormal and blood creatine kinase increased. Overdose: Specific treatment is not available for Lipitor overdose. Patient should be treated symptomatically, and supportive measures instituted, as required. Liver function tests should be performed and serum CK levels should be monitored. Due to extensive atorvastatin binding to plasma proteins, haemodialysis is not expected to significantly enhance atorvastatin clearance. Pharmaceutical precautions: Keep in a dry place. Store below 30 °C. Do not use Lipitor after the expiry date which is stated on the carton after EXP: The expiry date refers to the last day of that month. Keep out of the sight and reach of children. Reference: Lipitor SmPC Gulf States & Iraq revision dated: January 2019; for UAE (Registered Lipitor 10mg,20mg,40mg & 80mg), Qatar (Registered Lipitor 10mg, 20mg, 40mg & 80mg) & Iraq (Registered Lipitor 10mg, 20mg & 40mg); ), Bahrain (Registered Lipitor 10mg, 20mg, 40mg & 80mg), ), Oman (Registered Lipitor 10mg, 20mg & 40mg) and  June 2016 for Kuwait (Registered Lipitor 10mg, 20mg, 40mg & 80mg);

Date of Document: May 2020.

Full prescribing information is available upon request

LIPI-2022-0503

International Treatment Guidelines for Dyslipidaemia

The International Treatment Guidelines for Dyslipidemia

The International Treatment Guidelines for Dyslipidaemia

Efficacy in Reducing Blood Pressure

Norvasc Efficacy in Reducing Blood Pressure

Norvasc Efficacy in Reducing Blood Pressure

Prevalence of CVD in Africa Middle East

The Prevelance of CVD in Africa Middleast

ACE study- The Prevelance of CVD in Africa Middleast

Reduction of Cardiovascular Events

Norvasc Reduction in Cardiovascular Events

Norvasc Reduction of Cardiovascular Events