Treatment of Dyslipidemia¹

As an adjunct to diet for reduction of total-C, LDL-C, apo B, and TG in adults, adolescents and children aged 10 years or older with primary hypercholesterolemia, heterozygous familial hypercholesterolemia, or combined (mixed) hyperlipidemia (Fredrickson Types IIa and IIb), elevated serum TG levels (Fredrickson Type IV), and for patients with dysbetalipoproteinemia (Fredrickson Type III) when response to diet and other non-pharmacological measures is inadequate.

Atorvastatin also raises high density lipoprotein cholesterol (HDL-C) and lowers the LDL/HDL and total-C/HDL ratios.

Atorvastatin is also indicated to reduce total-C and LDL-C in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Prevention of Cardiovascular Disease¹

To reduce the risk of myocardial infarction (MI) in adult hypertensive patients without clinically evident coronary heart disease (CHD), but with at least three additional risk factors for CHD such as age ≥55 years, male sex, smoking, left ventricular hypertrophy, other specified abnormalities on electrocardiogram (ECG), microalbuminuria or proteinuria, ratio of plasma total-C to HDL-C ≥6, or premature family history of CHD.

In adults with type 2 diabetes and without clinically evident CHD, but with multiple risk factors for CHD such as retinopathy, albuminuria, smoking or hypertension, LIPITOR is indicated to:

• Reduce the risk of MI
• Reduce the risk of stroke

In adults with clinically evident CHD, atorvastatin is indicated to:

• Reduce the risk of non-fatal MI
• Reduce the risk of fatal and non-fatal stroke
• Reduce the risk for revascularization procedures
• Reduce the risk of hospitalization for congestive heart failure (CHF)
• Reduce the risk of angina

PP-LIP-SGP-0136/27AUG2021

Adapted from: Stancu C, Sima A. J Cell Mol Med. 2001;5(4):378–87.²

Lipitor^® is a selective, competitive inhibitor of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme responsible for the conversion of HMG-CoA to mevalonate, a precursor of sterols, including cholesterol. Triglycerides and cholesterol in the liver are incorporated into VLDL and released into the plasma for delivery to peripheral tissues. LDL is formed from very low-density lipoprotein (VLDL) and is catabolized primarily through the high-affinity LDL receptor.¹

Lipitor^® lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.¹

Lipitor^® reduces LDL production and the number of LDL particles. Atorvastatin produces a profound and sustained increase in LDL receptor activity coupled with a beneficial change in the quality of circulating LDL particles. Atorvastatin is effective in reducing LDL in patients with homozygous familial hypercholesterolemia, a population that has not normally responded to lipid-lowering medication.¹

In a dose-response study, atorvastatin (10 mg-80 mg) reduced total-C (30%-46%), LDL-C (41%-61%), apo B (34%-50%), and TG (14%-33%). These results are consistent in patients with heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia, and mixed hyperlipidemia, including patients with non-insulin-dependent diabetes mellitus.¹

PP-LIP-SGP-0136/27AUG2021

1.1 Proven outcomes

Powerful LDL-C Reductions in Every Dose—A Good Reason to Choose LIPITOR^®

In a dose-response study, Atorvastatin (10 mg – 80 mg) reduced total-C (30%-46%), LDL-C (41%-61%), apo B (34%-50%) and TG (14%-33%)¹

2018 /AHA Cholesterol Guidelines

• Recommend high-intensity statin therapy in patients aged <75 years with clinical ASCVD* to achieve ≥50% reduction in LDL-C levels²
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^2,†

2020 AACE/ACE Guideline

• Recommend statin therapy in patients who are at extreme risk^‡ to achieve LDL-C goal of <55 mg/dL for secondary prevention³

2016 NICE CVD Risk Update

• Recommends atorvastatin 20 mg-80 mg—a dose that lowers LDL-C by >40%—for the primary and secondary prevention of CVD⁴

*Clinical atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.

^†Evaluation of the potential for ASCVD risk reduction, adverse effects, and drug–drug interactions, as well as patient frailty and patient preferences.

^‡Progressive ASCVD including unstable angina in patients after achieving an LDL-C <70 mg/dL, established clinical cardiovascular disease in patients with DM, CKD 3/4, or HeFH, and history of premature ASCVD (<55 male, <65 female).

1.2 Multiple Risk factors

Prevent CV Events—A Good Reason to Give Patients With CV Risk Factors LIPITOR^®

In the ASCOT-LLA trial in patients with hypertension and ≥3 additional CV risk factors, LIPITOR 10 mg reduced the risk of nonfatal MI and fatal CHD by 36% compared with placebo^5*

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 study⁵

*ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm): Double-blind, placebo-controlled study including 10,305 hypertensive patients treated with antihypertensive therapy, without a previous CHD but with TC ≤251 mg/dL (6.5 mmol/L) randomized to LIPITOR 10 mg (n=5168) or placebo (n=5137). Patients also had ≥3 of the following additional CV risk factors: left ventricular hypertrophy, other specified abnormalities on ECG, type 2 diabetes, peripheral arterial disease, previous stroke or transient ischemic attack, male sex, aged ≥55 years, microalbuminuria or proteinuria, smoking, plasma TC:HDL-C ratio ≥6, or family history of premature CHD. Primary endpoint: nonfatal MI and fatal CHD. Mean baseline LDL-C and HDL-C were 131 mg/dL and 50 mg/dL (3.4 mmol/L and 1.3 mmol/L). The ASCOT-LLA study was stopped after 3.3 years (median) of a planned 5-year follow-up due to a significant reduction in CV outcomes among hypertensive in the lipid-lowering arm (LLA).⁵

Prevent CV Events in The Long-Term A Good Reason to Give Patients With CV Risk Factors LIPITOR^®

ASCOT* Legacy Study: Long-term benefits with significantly fewer cardiovascular-related deaths with atorvastatin vs placebo in the LLA⁸

The ASCOT Legacy Study evaluated long-term mortality data from patients in the ASCOT Study, approximately 16 years after entry into trial and 10 years after trial closure⁸

*ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm): Double-blind, placebo-controlled study including 10,305 hypertensive patients treated with antihypertensive therapy, and without a history of CHD and with TC ≤250 mg/dL (6.4 mmol/L) randomized to LIPITOR 10 mg (n=5168) or placebo (n=5137). Patients also had ≥3 of the following additional CV risk factors: left ventricular hypertrophy, other specified abnormalities on ECG, type 2 diabetes, PAD, previous stroke or transient ischemic attack, male sex, aged ≥55 years, microalbuminuria or proteinuria, smoking, plasma TC: HDL-C ratio ≥6, or family history of premature CHD. Primary endpoint: nonfatal MI and fatal CHD. Mean baseline LDL-C and HDL-C were 132 mg/dL and 50 mg/dL (3.4 mmol/L and 1.3 mmol/L). The ASCOT-LLA study was stopped after 3.3 years of a planned 5-year follow-up due to a significant reduction in CV outcomes among hypertensive patients with normal cholesterol levels who were on atorvastatin treatment.⁵

1.3 Diabetes

Diabetes + Hypertension

Reduce CV Risk—A Good Reason to Give Patients With Hypertension and Diabetes LIPITOR^{® 6,7}

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 placebo^6*

2016 NICE CVD Risk Update

• Recommends atorvastatin 20 mg for the primary prevention of CVD in patients with type 2 diabetes and a ≥10% 10-year risk of developing CVD⁴

2020 ADA Guideline

• Recommend statin therapy for patients with diabetes aged 20-39 years with additional risk factors for ASCVD along with the lifestyle therapy⁹
• Recommend moderate-intensity statin therapy for patients with diabetes aged 40-75 years without ASCVD⁹
• Recommend high-statin therapy for patients of all ages with diabetes and ASCVD, and aged 50-70 years with diabetes and >1 ASCVD risk factor⁹

2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease

• Recommend moderate-intensity statin therapy in patients with diabetes aged 40-75 years¹⁰
• Recommend high-intensity statin therapy in adults with diabetes with >1 ASCVD risk factor to reduce LDL-C levels by ≥50%¹⁰

*ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm): Double-blind, placebo-controlled study including 10,305 hypertensive patients treated with antihypertensive therapy and without a previous MI with TC ≤250 mg/dL (6.5mmol/L) were randomized to LIPITOR 10 mg (n=5168) or placebo (n=5137). Patients also had ≥3 of the following additional CV risk factors: left ventricular hypertrophy, other specified abnormalities on ECG, type 2 diabetes, peripheral arterial disease, previous stroke or transient ischemic attack, male sex, aged ≥55 years, microalbuminuria or proteinuria, smoking, plasma TC:HDL-C ratio ≥6, or family history of premature CHD. The 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. This analysis includes the 2532 patients with diabetes randomized to LIPITOR (n=1258) or placebo (n=1274).^5,6

Significant CV Risk Reduction—A Good Reason to Give Patients With Diabetes LIPITOR^{® 11}

In the CARDS trial in patients with type 2 diabetes and ≥1 risk factor, LIPITOR 10 mg reduced the risk of major CV events by 37% compared with placebo^11*

LIPITOR 10 mg also reduced the risk of MI by 42% (P=0.007)¹

2016 NICE CVD Risk Update

• Recommends atorvastatin 20 mg for the primary prevention of CVD in patients with type 2 diabetes and a ≥10% 10-year risk of developing CVD⁴

2020 ADA Guideline

• Recommend statin therapy for patients with diabetes aged 20-39 years with additional risk factors for ASCVD along with the lifestyle therapy⁹
• Recommend moderate-intensity statin therapy for patients with diabetes aged 40-75 years without ASCVD⁹
• Recommend high-statin therapy for patients of all ages with diabetes and ASCVD, and aged 50-70 years with diabetes and >1 ASCVD risk factor⁹

2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease

• Recommend moderate-intensity statin therapy in patients with diabetes aged 40-75 years¹⁰
• Recommend high-intensity statin therapy in adults with diabetes with >1 ASCVD risk factor to reduce LDL-C levels by ≥50%¹⁰

*CARDS (Collaborative AtoRvastatin Diabetes Study): Double-blind, prospective study in which 2838 patients aged 40-75 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. The trial was terminated 2 years earlier than planned due to significant benefits of atorvastatin. The median duration of follow-up was 4 years in the atorvastatin group and 3.9 years in the placebo group.¹¹

Stroke Risk Reduction—A Good Reason to Give Patients With Diabetes LIPITOR^{® 12}

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 placebo^12*

The lowest mean LDL-C level reached with LIPITOR in this study was 68 mg/dL (1.8 mmol/L)¹¹

*CARDS (Collaborative Atorvastatin Diabetes Study): Double-blind, prospective study in which 2838 patients aged 40-75 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 (4.1 mmol/L), TG ≤600 mg/dL (6.8 mmol/L) 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 3.9 years; the CARDS trial was terminated at 3.9 years–2 years earlier than planned–due to highly significant benefits of atorvastatin.^11,12

1.4 Coronary Heart Disease

Reduce CV Events—A Good Reason to Give CHD Patients LIPITOR^{® 14}

In the TNT trial in patients with CHD, LIPITOR 80 mg significantly reduced the rate of major CV events compared with LIPITOR 10 mg¹⁴*

2016 NICE CVD Risk Update

• Recommends atorvastatin as first-line treatment for the prevention of CVD⁴

2019 ESC/EAS Dyslipidemia Guidelines

• Recommend high-intensity statin up to the highest tolerated dose as first-line treatment to achieve goals set for the specific level of risk¹³

2018 ACC/AHA Cholesterol Guidelines

• Recommend high-intensity statin therapy in patients aged <75 years with clinical ASCVD‡ to achieve ≥50% reduction in LDL-C levels²
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^2,§

*TNT (Treating to New Targets): Double-blind, prospective study in which 10,001 patients with stable, clinically evident CHD and LDL-C <130 mg/dL (3.4 mmol/L) were randomized to LIPITOR 10 mg (n=5006) or 80 mg (n=4995).

The primary endpoint was the first major CV event (death from CHD, nonfatal, non–procedure-related MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke). Median follow-up was 4.9 years.¹⁴

‡Clinical atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.²

§Evaluation of the potential for ASCVD risk reduction, adverse effects, and drug–drug interactions, as well as patient frailty and patient preferences.²

CHD + Diabetes

Reduce CV Events—A Good Reason to Give Patients with CHD and Type 2 Diabetes LIPITOR^{® 15}

In the TNT trial post hoc subgroup analysis in patients with stable CHD and type 2 diabetes, LIPITOR 80 mg significantly reduced the rate of major CV events compared with LIPITOR 10 mg^15*

2018 ACC/AHA Cholesterol Guidelines

Recommend moderate-intensity statin therapy for diabetes patients 40-75 years of age regardless of estimated 10-year ASCVD risk²

*TNT (Treating to New Targets): Double-blind study including 1501 patients with stable, clinically evident CHD, diabetes, and LDL-C <130 mg/dL (3.4 mmol/L). Patients were randomized to LIPITOR 10 mg (n=753) or 80 mg (n=748). Primary endpoint: first major CV event (death from CHD, nonfatal, non–procedure-related MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke). Median baseline LDL-C was 0.6mg/dL (2.5 mmol/L).¹⁵

CHD + CKD

Reduce CV Events—A Good Reason to Give Patients With CHD and CKD LIPITOR^{® 16}

In a TNT post hoc subgroup analysis in patients with stable CHD and CKD, LIPITOR 80 mg significantly reduced the rate of major CV events compared with LIPITOR 10 mg^16*

2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease

• Recommend moderate-intensity statin therapy in adult patients at intermediate risk and patients at borderline risk with risk-enhancing factors¹⁰

2018 ACC/AHA Cholesterol Guideline

• Recommend high-intensity statin therapy in patients aged <75 years with clinical ASCVD‡ to achieve ≥50% reduction in LDL-C levels²
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^2,§

*TNT (Treating to New Targets): Double-blind, prospective study in which 10,001 patients with stable, clinically evident CHD and LDL-C <130 mg/dL (3.4 mmol/L) were randomized to LIPITOR 10 mg (n=5006) or 80 mg (n=4995).

The primary endpoint was the first major CV event (death from CHD, nonfatal, non–procedure-related MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke). Median follow-up was 5.0 years.¹⁶

‡Clinical atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.²

§Evaluation of the potential for ASCVD risk reduction, adverse effects, and drug–drug interactions, as well as patient frailty and patient preferences.²

CHD +CHF

Reduce Hospitalizations—A Good Reason to Give CHD Patients With Previous CHF LIPITOR^{® 17}

Heart failure affects an estimated 23 million people worldwide¹⁸

In a TNT post hoc subgroup analysis in patients with stable CHD and a history of CHF, LIPITOR 80 mg significantly reduced the rate of hospitalizations due to heart failure compared with LIPITOR 10 mg^17*

*TNT (Treating to New Targets): Double-blind study including 781 patients with stable, clinically evident CHD, a history of heart failure, and LDL-C <130 mg/dL (3.4 mmol/L). Patients were randomized to LIPITOR 10 mg (n=404) or 80 mg (n=377). Primary endpoint: first major CV event (death from CHD, nonfatal, non–procedure-related MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke). Median follow-up was 4.9 years.¹⁷

CHD

Prevent CV Events—A Good Reason to Give Patients With CHD LIPITOR^{® ¹9}

In the ALLIANCE trial in patients with established CHD, LIPITOR at a mean dose of 40.5 mg reduced the risk of non-fatal MI by nearly half compared with usual care^19*

2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease

• Recommend moderate-intensity statin therapy in adult patients at intermediate risk and patients at borderline risk with risk-enhancing factors¹⁰

2018 ACC/AHA Cholesterol Guideline

• Recommend high-intensity statin therapy in patients aged ≤75 years with clinical ASCVD^‡ to achieve ≥50% reduction in LDL-C levels²
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^2,§

*ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events): Prospective study in which 2442 patients with known CHD and hyperlipidemia (LDL-C 110-200 mg/ dL [2.8-5.2 mmol/L] for lipid-treated patients, 130-250 mg/dL [3.4-6.5 mmol/L] for untreated patients) were randomized to aggressive treatment with LIPITOR (n=1217) or usual care (n=1225) and followed for a mean of 51.5 months. LIPITOR-treated patients were titrated to LDL-C goals of <80 mg/dL [2.1 mmol/L] or a maximum dose of 80 mg/day. Mean dose of LIPITOR was 40.5 mg/day. Usual-care patients received any treatment deemed appropriate by their physicians, including lipid-lowering treatment. The primary efficacy endpoint was the time from randomization to the first occurrence of a primary CV event (cardiac death, nonfatal MI, resuscitated cardiac arrest, cardiac revascularization, or unstable angina requiring hospitalization).¹⁹

‡Clinical atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.²

§Evaluation of the potential for ASCVD risk reduction, adverse effects, and drug–drug interactions, as well as patient frailty and patient preferences.²

Effectively Reduce CV Risk—A Good Reason to Give Patients With CHD LIPITOR^{® 19}

In the ALLIANCE trial in patients with established CHD, LIPITOR at a mean dose of 40.5 mg significantly reduced the rate of CV events compared with usual care¹⁹

2020 AACE/ACE Guidelines

• Recommend statin therapy in patients who are at extreme risk‡ to achieve LDL-C goal of <55 mg/dL for secondary prevention³
• Recommend statin therapy in patients who are very high-risk with established coronary, carotid, and peripheral vascular disease, or diabetes, and also have at least 1 additional risk factor, to achieve LDL-C <70 mg/dL³
• Recommend statin therapy in patients who are at high-risk and very high-risk categories to further lower LDL-C beyond established targets for additional ASCVD event reduction³

*ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events): Prospective study in which 2442 patients with known CHD and hyperlipidemia (LDL-C 110-200 mg/ dL [2.8-5.2 mmol/L] for lipid-treated patients, 130-250 mg/dL [3.4-6.5 mmol/L] for untreated patients) were randomized to aggressive treatment with LIPITOR (n=1217) or usual care (n=1225) and followed for a mean of 51.5 months. LIPITOR-treated patients were titrated to LDL-C goals of <80 mg/dL [2.1 mmol/L] or a maximum dose of 80 mg/day. Median dose of LIPITOR was 40.5 mg/day. Usual-care patients received any treatment deemed appropriate by their physicians, including lipid lowering treatment. The primary efficacy endpoint was the time from randomization to the first occurrence of a primary CV event (cardiac death, nonfatal MI, resuscitated cardiac arrest, cardiac revascularization, or unstable angina requiring hospitalization).¹⁹

‡Progressive ASCVD including unstable angina in patients after achieving an LDL-C <70 mg/dL, established clinical cardiovascular disease in patients with DM, CKD 3/4, or HeFH, and history of premature ASCVD (<55 male, <65 female).³

Reduce CV Risk—A Good Reason to Give Patients With CHD LIPITOR^{® 20}

In the GREACE trial in patients with CHD, LIPITOR 10 mg to 80 mg reduced the risk of death by 43% and the risk of coronary death by 47% compared with usual care²⁰

2020 AACE/ACE Guidelines

• Recommend statin therapy in patients who are at extreme risk‡ to achieve LDL-C goal of <55 mg/dL for secondary prevention³
• Recommend statin therapy in patients who are very high-risk with established coronary, carotid, and peripheral vascular disease, or diabetes, and also have at least 1 additional risk factor, to achieve LDL-C <70 mg/dL³
• Recommend statin therapy in patients who are at high-risk and very high-risk categories to further lower LDL-C beyond established targets for additional ASCVD event reduction³

*GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation): Prospective trial in which 1600 consecutive patients aged <75 years with established CHD were randomized to LIPITOR 10 mg titrated as necessary up to 80 mg to reach LDL-C <100 mg/dL (n=800) or usual care, which could include lipid-lowering treatment (n=800). Primary endpoints were death, nonfatal MI, unstable angina, CHF, revascularization and stroke. The mean LIPITOR dosage was 24 mg/day; mean follow-upwas 3 years.²⁰

†Progressive ASCVD including unstable angina in patients after achieving an LDL-C <70 mg/dL, established clinical cardiovascular disease in patients with DM, CKD 3/4, or HeFH, and history of premature ASCVD (<55 male, <65 female).³

1.5 Acute Coronary Syndrome (ACS)

Reduce CV Risk—A Good Reason to Give ACS Patients LIPITOR^{® 21}

In the PROVE IT trial in patients with ACS, LIPITOR 80 mg significantly reduced the rate of death or a major CV event compared with pravastatin 40 mg²¹

• The benefit of high-dose atorvastatin as compared with standard-dose pravastatin emerged as early as 30 days and was consistent over time²¹
• In a PROVE IT analysis, LIPITOR 80 mg did not increase the risk of kidney injury compared to pravastatin 40 mg²²

2019 ESC/EAS Dyslipidemia Guidelines

• Recommend initiation or continuation of high-dose statins in all ACS patients without any contraindication or definite history of intolerance, irrespective of initial LDL-C levels¹³

*PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22): Double-blind, prospective study in which 4162 patients hospitalized for ACS within the preceding 10 days, with TC ≤240 mg/dL (6.2 mmol/L) (or ≤200 mg/dL [5.2 mmol/L] if on long-term lipid-lowering therapy), were randomized to LIPITOR 80 mg (n=2099) or pravastatin 40 mg (n=2063). The primary endpoint was a composite of all-cause mortality, MI, unstable angina requiring hospitalization, revascularization, and stroke. Follow-up lasted 18-36 months (mean 24).²¹

ACS + Diabetes

Reduce Acute Cardiac Events—A Good Reason to Give Patients With ACS and Diabetes LIPITOR^{® 23}

In a PROVE IT post hoc subgroup analysis in patients with recent ACS and diabetes, LIPITOR 80 mg significantly reduced the rate of acute cardiac events compared with pravastatin 40 mg²³

2020 AACE/ACE Guidelines

Recommend statins in patients who are at extreme risk, including patients with established clinical CVD in patients with diabetes, to achieve an LDL-C goal of <55 mg/dL³

*PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22): Analysis of subjects with diabetes (n=978) out of 4162 patients hospitalized for ACS within the preceding 10 days, with TC ≤240 mg/dL (6.2 mmol/L) (or ≤200 mg/dL [5.2 mmol/L] if on long-term lipid-lowering therapy). Patients were randomized to LIPITOR 80 mg (n=499) or pravastatin 40 mg (n=479). The primary endpoint was a composite of death, MI, unstable angina requiring rehospitalization, revascularization, or stroke; also assessed was a triple endpoint of acute cardiac events (death, MI, or unstable angina requiring rehospitalization).^21,23

ACS

Reduce CV Events, Including Stroke at 16 Weeks – A Good Reason to Give Patients With ACS LIPITOR^{® 24}

In the MIRACL trial in patients with ACS, LIPITOR reduced the risk of fatal and nonfatal stroke by half compared with placebo²⁴

2018 ACC/AHA Cholesterol Guideline

• Recommend high-intensity statin therapy in patients aged ≤75 years with clinical ASCVD† to achieve ≥50% reduction in LDL-C levels²
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^2,‡

2013 ACCF/AHA Guideline

• Recommend LIPITOR 80 mg in all patients with ST–segment-elevated myocardial infarction and without contraindications²⁵

^†Clinical atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.²

^‡Evaluation of the potential for ASCVD risk reduction, adverse effects, and drug–drug interactions, as well as patient frailty and patient preferences.²

1.6 Stroke/ TIA

Prevent Stroke—A Good Reason to Give High-risk Patients With Previous Stroke/TIA LIPITOR^{® 26}

In the SPARCL trial in patients with a previous stroke/TIA, LIPITOR 80 mg significantly reduced the rate of fatal or nonfatal stroke compared with placebo^26*

2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease

Recommend moderate-intensity statin therapy in adult patients at intermediate risk and patients at borderline risk with risk-enhancing factors¹⁰

2019 AHA/ASA Guideline

• Recommend high-intensity statin therapy in patients ≤75 years with clinical ASCVD, to achieve ≥50% reduction in LDL-C levels²⁸
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^28*

*Potential for ASCVD risk reduction, adverse effects, and drug-drug interactions, as well as patient frailty and patient preferences²⁸

Prevent CV events—A Good Reason to Choose LIPITOR® in Patients With Previous Stroke/TIA and No Known CHD²⁹

In a post hoc analysis of the SPARCL trial, the total number of vascular events prevented with atorvastatin 80 mg was more than twice the number of first events prevented, with significant reductions in total vascular, cerebrovascular, coronary, and peripheral events.²⁹

2020 AACE/ACE Guidelines

• Recommend statin therapy in patient who are very-risk with established coronary, carotid, and peripheral vascular disease, or diabetes, and also have at least 1 additional risk factor, to achieve LDL-C <70 mg/dL³
• Recommend statin therapy in patients who are at high-risk and very high-risk categories to further lower LDL-C beyond established targets for additional ASCVD event reduction³

2019 AHA/ASA Guidelines

• Recommend high-intensity statin therapy in patients ≤75 years with clinical ASCVD to achieve ≥50% reduction in LDL-C levels²⁸
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^28,†
• Recommend non-statins in patients with clinical ASCVD receiving highest tolerated statin dose, are at very high risk, and ≥ 70 mg/dL (≥1.8 mmol/L) LDL-C level²⁸

Stroke+TIA

Reduce CV Events—A Good Reason to Give High-risk Patients With Previous Stroke/TIA LIPITOR^{® 26}

In the SPARCL trial in patients with a previous stroke/TIA, LIPITOR 80 mg reduced the risk of any coronary event by 42% compared with placebo^26*

LIPITOR 80 mg also provided a 49% relative risk reduction in non-fatal MI compared with placebo (P<0.001) and brought patients to a mean LDL-C level of 73 mg/dL (1.9 mmol/L)²⁶

2019 AHA/ASA Guidelines

• Recommend high-intensity statin therapy in patients ≤75 years with clinical ASCVD to achieve ≥50% reduction in LDL-C levels²⁸
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^28,†

^† Potential for ASCVD risk reduction, adverse effects, and drug-drug interaction, as well as patient frailty and patient preferences.²⁸

Stroke + ASCVD

Prevent CV events – A Good Reason to Target LDL-C <70 mg/dL in Patients With Previous Stroke and ASCVD³⁰

In the Treat Stroke to Target (TST) trial in patients with ischemic stroke, targeting LDL-C to <70 mg/dL significantly prevented major vascular events vs a target LDL-C of 100±10 mg/dL^30,31

2020 AACE/ACE Guidelines

• Recommend statin therapy in patient who are very-risk with established coronary, carotid, and peripheral vascular disease, or diabetes, and have at least 1 additional risk factor, to achieve LDL-C <70 mg/dL³
• Recommend statin therapy in patients who are at high-risk and very high-risk categories to further lower LDL-C beyond established targets for additional ASCVD event reduction³

2019 AHA/ASA Guidelines

• Recommend high-intensity statin therapy in patients ≤75 years with clinical ASCVD to achieve ≥50% reduction in LDL-C levels²⁸
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^28,†
• Recommend non-statins in patients with clinical ASCVD receiving highest tolerated statin dose, are at very high risk, and ≥ 70 mg/dL (≥1.8 mmol/L) LDL-C level²⁸

^†Potential for ASCVD risk reduction, adverse effects, and drug-drug interactions, as well as patient frailty and patient preferences.

a. Post – MI

Reduce CVD—A Good Reason to Give Patients With Previous MI LIPITOR^{® 32}

In the IDEAL trial in patients with previous MI, LIPITOR 80 mg significantly reduced the risk of any CVD compared with simvastatin 20 mg^32*

*IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering): Prospective, open-label, blinded endpoint evaluation study including 8888 patients with a history of acute MI who were randomized to LIPITOR 80 mg (n=4439) or simvastatin 20 mg (n=4449). If TC >190 mg/dL (5.0 mmol/L) after 24 weeks, the dose of simvastatin could be increased to 40 mg/day. Primary endpoint: occurrence of a major coronary event, defined as coronary death,

confirmed nonfatal acute MI, or cardiac arrest with resuscitation, was reduced by 11% (P=0.07). Occurrence of any CVD was reduced by 16% (P<0.001). Mean baseline LDL-C and HDL-C were 122 mg/dL and 46 mg/dL (3.1 mmol/L and 1.2 mmol/L).³²

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Atorvastatin is generally well-tolerated. Adverse reactions have usually been mild and transient. In the atorvastatin placebo-controlled clinical trial database of 16,066 (8755 LIPITOR vs. 7311 placebo) patients treated for a median period of 53 weeks, 5.2% of patients on atorvastatin discontinued due to adverse reactions compared to 4.0% of patients on placebo.¹

The most frequent (≥1%) adverse effects that may be associated with atorvastatin therapy, reported in patients participating in placebo-controlled clinical studies include.¹

Infections and infestations: nasopharyngitis.

Metabolism and nutrition disorders: hyperglycemia.

Respiratory, thoracic and mediastinal disorders: pharyngolaryngeal pain, epistaxis.

Psychiatric disorders: insomnia.

Nervous system disorders: headache.

Gastrointestinal disorders: nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence.

Musculoskeletal and connective tissue disorders: arthralgia, pain in extremity, musculoskeletal pain, muscle spasms, myalgia, joint swelling.

General disorders and administration site conditions: asthenia.

Investigations: liver function test abnormal, blood creatine phosphokinase increased.

Additional adverse effects reported in atorvastatin placebo-controlled clinical trials include:

Metabolism and nutrition disorders: hypoglycemia, hyperglycemia, anorexia.

Psychiatric disorders: nightmare.

Eye disorders: vision blurred.

Ear and labyrinth disorders: tinnitus.

Nervous system disorders: peripheral neuropathy, paresthesia.

Gastrointestinal disorders: abdominal discomfort, eructation, pancreatitis, vomiting.

Hepatobiliary disorders: hepatitis, cholestasis.

Skin and subcutaneous tissue disorders: alopecia, pruritus, rash, urticaria.

Musculoskeletal and connective tissue disorders: myopathy, myositis, muscle cramps, muscle fatigue, neck pain.

Reproductive system and breast disorders: impotence.

General disorders and administration site conditions: malaise, pyrexia.

Investigations: white blood cells urine positive.

Not all effects listed above have been causally associated with atorvastatin therapy.

Pediatric Population

The clinical safety database includes safety data for 249 pediatric patients who received atorvastatin, among which 7 patients were <6 years old, 14 patients were in the age range of 6 to 9, and 228 patients were in the range of 10 to 17.

Nervous system disorders: Common: Headache.

Gastrointestinal disorders: Common: Abdominal pain.

Investigations: Common: Alanine aminotransferase increased, blood creatine phosphokinase increased.

Based on the data available, frequency, type and severity of adverse reactions in children are expected to be the same as in adults. There is currently limited experience with respect to long-term safety in the pediatric population.

Patients treated with atorvastatin had an adverse experience profile generally similar to that of patients treated with placebo, the most common adverse experiences observed in both groups, regardless of causality assessment, were infections.

No clinically significant effect on growth and sexual maturation was observed in a 3-year study in children ages 6 and above based on the assessment of overall maturation and development, assessment of Tanner Stage, and measurement of height and weight. The safety and tolerability profile in pediatric patients was similar to the known safety profile of atorvastatin in adult patients.

Post-marketing Experience

In post-marketing experience, the following additional undesirable effects have been reported:

Blood and lymphatic system disorders: thrombocytopenia;

Immune system disorders: allergic reactions (including anaphylaxis);

Injury, poisoning and procedural complications: tendon rupture;

Metabolism and nutrition disorders: weight gain;

Nervous system disorders: hypoesthesia, amnesia, dizziness, dysgeusia;

Gastrointestinal disorders: pancreatitis;

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, erythema multiforme, bullous rashes;

Musculoskeletal and connective tissue disorders: rhabdomyolysis, immune-mediated necrotizing myopathy, myositis, back pain;

General disorders and administration site conditions: chest pain, peripheral edema, fatigue.

There have been rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally non-serious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Summary

An Established Safety Profile Across the Dose Range—A Good Reason to Choose LIPITOR

• LIPITOR has a flexible starting dose for new patients (10, 20, or 40 mg)¹
• According to the latest international guidelines, patients should be titrated to the highest tolerable statin dose before considering adding ezetimibe or other non-statin therapies if LDL-C goals are not reached^3,4

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Lipitor^® dosage¹

• Dose range: 10 to 80 mg once daily .
• Recommended start dose: 10 or 20 mg once daily .
• Patients requiring large LDL-C reduction (>45%) may start at 40 mg once daily .
• Pediatric patients with hypercholesterolimia: Use should only be carried out by physicians experienced in the treatment of pediatric hyperlipidemia and patients should be re-evaluated on a regular basis to assess progress; For patients aged 10 years and above, the recommended starting does is 10 mg daily with titration up to 20 mg daily. Titration should be conducted according to the individual response and tolerability in pediatric patients. Safety information for pediatric patients treated with doses above 20 mg, corresponding to about 0.5 mg/kg, is limited.

Lipitor^® tablets are available in three strengths¹:

• 10 mg of atorvastatin.
• 20 mg of atorvastatin.
• 40 mg of atorvastatin.

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Note: Please refer to the full prescribing information before prescribing

LIPITOR

Content: Atorvastatin

Indications: Adjunct to diet for reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B and triglycerides in adults, adolescents and children ≥10 year with primary hypercholesterolemia, heterozygous familial hypercholesterolemia or combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb), elevated serum triglyceride levels (Fredrickson type IV) and for patients with dysbetalipoproteinemia (Fredrickson type III) when response to diet and other nonpharmacological measures is inadequate. Raises HDL-cholesterol and lowers the LDL/HDL and total-C/HDL ratios. Reduction of total-C & LDL-C in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or when such treatments are not available. Reduce the risk of Myocardial Infarction (MI) in adult hypertensive patients without clinically evident Coronary Heart Disease (CHD), but with at least 3 additional risk factors for CHD eg, age ≥55 years, male sex, smoking, left ventricular hypertrophy, other specified abnormalities on ECG, microalbuminuria or proteinuria, ratio of plasma total-C to HDL-cholesterol ≥6, or premature family history of CHD. Reduce the risk of MI or stroke in adults with type 2 diabetes and without clinically evident CHD, but with multiple risk factors for CHD eg, retinopathy, albuminuria, smoking or hypertension. Reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure and angina in adults with clinically evident CHD.

Dosage: Initially 10-20 mg once daily. Patients who require a large reduction in LDL-C (>45%) may be started at 40 mg once daily. Dosage range: 10-80 mg once daily. Adult Prevention of Cardiovascular disease Primary: 10 mg once daily; secondary: 10-80 mg once daily. Primary hypercholesterolemia and combined (mixed) hyperlipidemia 10mg once daily. Homozygous familial hypercholesterolemia 80 mg. Children ≥10 year Hypercholesterolemia/hyperlipidemia Initially 10 mg daily, may be titrated up to 20 mg daily.

Administration: Take with or without food. Avoid excessive consumption (>1 L/day) of grapefruit juice.

Contraindications: Hypersensitivity. Active liver disease or unexplained persistent elevations of serum transaminases >3 times the upper limit of normal. Women of childbearing potential not using adequate contraception. Pregnancy & lactation. Concomitant treatment with glecaprevir/pibrentasvir.

Special Precautions: Perform liver function tests before treatment and periodically thereafter. History of liver disease or substantial alcohol consumption. Discontinue use if markedly elevated creatine phosphokinase (CPK) levels occur or myopathy is diagnosed or suspected. Increased risk of myopathy with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, azole antifungals, colchicine, telaprevir, boceprevir or the combination of tipranavir/ritonavir. Carefully monitor patients for any signs and symptoms of muscle pain, tenderness or weakness particularly during the initial month of therapy and during any period of upward dosage titration. Temporarily withhold or discontinue use in any patient with an acute, serious condition suggestive of myopathy or having risk factors predisposing to development of renal failure secondary to rhabdomyolysis. There have been very rare reports of an immune-mediated necrotizing myopathy (IMNM) during or after treatment with some statins. Concomitant use with fusidic acid. Consider potential risk of hemorrhagic stroke before treatment in patients with recent (1-6 month) stroke or transient ischemic attack. Increase in HbA1c and fasting serum glucose levels. Periodic monitoring in patients at high risk of diabetes mellitus. Children <10 year.

Adverse Reactions: Nasopharyngitis; hyperglycaemia; pharyngolaryngeal pain, epistaxis; insomnia; headache; nausea, diarrhoea, abdominal pain, dyspepsia, constipation, flatulence; arthralgia, pain in extremity, musculoskeletal pain, muscle spasms, immune-mediated necrotizing myopathy, myalgia, joint swelling; asthenia; abnormal liver function test, increased blood creatine phosphokinase.

Drug Interactions: Increased risk of myopathy with cyclosporine, fibric acid derivatives, lipid-modifying doses of niacin and increased plasma concentration with CYP3A4 inhibitors (eg, erythromycin & azole antifungals). Increased bioavailability with organic anion-transporting polypeptide 1B1 inhibitors (eg, cyclosporine). Increased plasma concentration with clarithromycin, erythromycin, Protease Inhibitors, diltiazem, grapefruit juice (>1.2 L/day) and letermovir. Use not recommended in patients taking letermovir co-administered with cyclosporine. Dose of atorvastatin should not exceed 20 mg/day with concomitant use with elbasvir/grazoprevir or letermovir. Increased AUC with itraconazole. Decreased plasma concentration with CYP3A4 inducers (eg, efavirenz, rifampin), oral antacids containing Mg and Al hydroxide, colestipol. May increase concentration of digoxin and AUC of Oral Contraceptives (containing norethindrone and ethinyl estradiol). Cases of myopathy with colchicine. Increased risk of rhabdomyolysis with fusidic acid.

Presentation and Packing: FC tab (blister pack) 10 mg x 30's. 20 mg x 30's. 40 mg x 30's. Not all presentations may be available locally.

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