Atorvastatin is indicated as an adjunct to diet for the treatment of patients with elevated total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglycerides (TG) and to increase high density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial hypercholesterolemia), combined (mixed) hyperlipidemia (Fredrickson Types IIa and IIb), elevated serum TG levels (Fredrickson Type IV), and for patients with dysbetalipoproteinemia (Fredrickson Type III) who do not respond adequately to diet.

Atorvastatin is also indicated for the reduction of total-C and LDL-C in patients with homozygous familial hypercholesterolemia.

Prevention of Cardiovascular Disease

Statin Mode of Action¹

Adapted from Statin Mechanism of action and effects; J. Cell. Mol. Med. Vol. 5, No 4, 2001.

Lipitor^® (atorvastatin calcium) is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In patients with homozygous and heterozygous familial hypercholesterolemia, nonfamilial forms of hypercholesterolemia, and mixed dyslipidemia, atorvastatin reduces total-C, LDL-C, and apo B. Atorvastatin also reduces very low-density lipoprotein cholesterol (VLDL-C) and TG and produces variable increases in HDL-C.²

Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and subsequently cholesterol biosynthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.²

Atorvastatin 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.²

Atorvastatin is effective in reducing LDL-C in patients with homozygous familial hypercholesterolaemia, a population that has not usually responded to lipid-lowering medicinal products.²

Atorvastatin (10 mg – 80 mg) has been shown to reduce concentrations of total-C (30% - 46%), LDL-C (41% - 61%), apolipoprotein B (34% - 50%), and triglycerides (14% - 33%) in a dose response study. These results are consistent in patients with heterozygous familial hypercholesterolaemia, nonfamilial forms of hypercholesterolaemia, and mixed hyperlipidaemia, including patients with noninsulin-dependent diabetes mellitus.²

LDL: Low-density Lipoprotein; MCP-1: Monocyte Chemotactic Protein-1; M-CSF: Macrophage Colony-stimulating Factor; ROS: Reactive Oxygen Species; ox-LDL: Oxidized Low-density Lipoprotein; IEL: Intraepithelial Lymphocytes

Pack shot for illustration purpose only.

Adapted from Lipitor Dosage & Drug Information, MIMS Malaysia

HeFH: Heterozygous Familial Hypercholesterolemia

*Lipid levels should be analyzed within 2 to 4 weeks. Dose should be individualized according to baseline LDL-C levels, the goal of therapy, and patient response

Powerful LDL-C Reductions in Every Dose¹

Lipitor^® LDL-C Reductions¹

Lipitor^® also has proven TG reductions of 14% to 33% across the dose range²

Lipitor^® (Atorvastatin Calcium) Is Among the Two High Intensity Statins.³

Adapted from Grundy SM, et al. J Am Coll Cardiol 2019;73(24):3168–3209.

^$Although simvastatin 80 mg was evaluated in RCTs,initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy,including rhabdomyolysis.

Rosuvastatin 40mg is not available in Malaysia.

International Guidelines Recommended Statins for CV Prevention^3-5

2018 ACC/AHA Cholesterol Guidelines³

• Recommend high-intensity statin therapy in patients aged<75years with clinical ASCVD*to achieve ≥50% reduction in LDL-C levels³
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^3,†

2020 AACE/ACE Guideline⁴

• Recommend statin therapy in patients who are at extreme risk^‡ to achieve LDL-C goal of <55 mg/dL for secondary prevention⁴

2016 NICE CVD Risk Update⁵

• Recommends atorvastatin 20 mg-80 mg—a dose that lowers LDL-C by >40%—for the primary and secondary prevention of CVD⁵

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

LDL-C: Low Density Lipoprotein-Cholesterol; TG: Triglyceride; CV: Cardiovascular; CVD: Cardiovascular Disease; ACC/AHA: American College of Cardiology/American Heart Association; AACE/ACE: American Association of Clinical Endocrinology/American College of Endocrinology; NICE: National Institute for Health and Care Excellence

Early CV Benefits in patients with multiple CV risk factors^1,2

• 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 placebo (p=0.0005).²
• With reductions in CV risk in as early as 3 months, Lipitor^® works fast, empowering you to provide lifesaving benefits to your patients as early as possible.²

Based on ASCOT-LLA study: Of 19,342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10,305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being nonfatal myocardial infarction and fatal CHD. Data were analysed by intention to treat²

CV Outcome Benefit as Early as 6 Months^3,4

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

In CARDS, in patients with type 2 diabetes and ≥1 risk factor:-

• Lipitor^® 10mg reduced the risk of major CV events by 37% vs placebo (p=0.001).⁴
• Lipitor^® 10mg also reduced the risk of stroke by 48% vs placebo.⁴

ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm; CV: Cardiovascular; MI: Myocardial Infarction; CHD: Coronary Heart Disease; T2DM: Type II Diabetes Mellitus

CV risk reduction within days with Lipitor^® (Atorvastatin calcium)^5,6

In the PROVE IT trial, the benefit of high-dose Lipitor^® (Atorvastatin calcium) compared with standard-dose pravastatin emerged as early as 30 days and was consistent over time^‡5

In patients with acute coronary syndrome (ACS), Lipitor^® (Atorvastatin calcium) 80 mg significantly reduced the risk of death, myocardial infarction (MI), or recurrent hospitalization, with benefit seen as early as 15 days⁶

^‡PROVE IT-TIMI 22 was a double-blind, prospective study in which 4162 patients who were 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^® (Atorvastatin calcium) 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 for 18 to 36 months (mean 24 months).⁵

In the IMPROVE-IT trial, ezetimibe plus simvastatin demonstrated a modest reduction in CV events at 7 years^†8

• Adding ezetimibe to simvastatin demonstrated a modest benefit in reducing CV events⁷
• The treatment benefit was observed predominantly in patients with diabetes and in patients ≥75 years of age, representing smaller percentage of the overall patient population⁸

^†IMPROVE-IT was a randomized, double-blind, multicenter clinical trial designed to assess whether the use of the combination of ezetimibe and simvastatin improves clinical outcomes compared with simvastatin monotherapy in 18,144 patients with ACS.⁷

Patients with type 2 diabetes mellitus (T2DM) and elevated cardiovascular (CV) risk benefit from interventions that significantly reduce major CV events, myocardial infarctions, and strokes. Clinical trials such as CARDS Trial highlight reductions of up to 37% in major CV events and up to 48% in stroke risk, with effective lowering of LDL-C to target levels. Current clinical guidelines recommend targeted approaches to minimize cardiovascular complications in diabetes and chronic kidney disease (CKD) patients.

Reduce Mortality and Major CV Event¹

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 mg¹

• The benefit of high-dose atorvastatin as compared with standard-dose pravastatin emerged as early as 30 days and was consistent over time¹
• In a PROVE IT analysis, Lipitor^® 80 mg did not increase the risk of kidney injury compared to pravastatin 40 mg²

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 levels³

*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).¹

Reduce Acute Cardiac Events⁴

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 mg⁴

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/dL (1.4mmol/L)⁵

*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).^1,4

Reduce CV Events, Including Stroke at 16 Weeks⁶

In the MIRACL trial in patients with ACS, Lipitor^® reduced the risk of fatal and nonfatal stroke by half compared with placebo⁶

 

2018 ACC/AHA Cholesterol Guideline⁷

• Recommend high-intensity statin therapy in patients aged ≤75 years with clinical ASCVD† to achieve ≥50% reduction in LDL-C levels⁷
• Recommend moderate- or high-intensity statins in patients >75 years with clinical ASCVD after evaluating their clinical condition^7,‡

2013 ACCF/AHA Guideline⁸

• Recommend LIPITOR 80 mg in all patients with ST–segment-elevated myocardial infarction and without contraindications⁸

†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.⁷

‡Evaluation of the potential for ASCVD risk reduction, adverse effects, and drug–drug interactions, as well as patient frailty and patient preferences.⁷

ACS: Acute Coronary Syndrome; CV: Cardiovascular; ESC/EAS: European Society of Cardiology/European Atherosclerotic Society; ACC/AHA: American College of Cardiology/American Heart Association; AACE/ACE: American Association of Clinical Endocrinology/American College of Endocrinology; NICE: National Institute for Health and Care Excellence; ADA: American Diabetic Association; ACCF/AHA: American College of Cardiology Foundation/American Heart Association

Effective management of coronary heart disease (CHD) is essential, particularly for patients with comorbidities like diabetes, chronic kidney disease, or heart failure. Latest studies have proven that personalized treatment based on age, risk factors, and cholesterol levels improves patient outcomes. Guidelines prioritize this tailored approach, recommending interventions that address both cardiovascular and comorbid conditions. Comprehensive analysis and detailed guidelines are available online for further reference.

Intensive lipid-lowering therapy is proven to reduce the risk of recurrent stroke, heart attacks, and other vascular events in patients with a history of ischemic stroke or transient ischemic attack (TIA). This therapy significantly lowers both fatal and nonfatal strokes, as well as coronary and peripheral events when compared with placebo, based on SPARCL Trial. Prioritizing lipid management is essential for poststroke prevention and long-term cardiovascular protection.

The 2023 American Heart Association (AHA) Scientific Sessions took place in Philadelphia, USA on November 10–13, 2023. This newsletter summarizes key presentations from the meeting concerning dyslipidemia.

Update 1. Study shows that statins reduce risk of dementia and Alzheimer’s disease

Study shows that statin use was associated with reductions in dementia and Alzheimer’s disease¹

In “Commonly used treatments in cardiovascular diseases and memory loss: is it time to ‘think’ about it?” Jennifer Dearborn-Tomazos (Boston, MA) presented a systematic review and meta-analysis of 46 observational cohort and case control studies comparing statin users with non-users.¹ Statin use was associated with a 20% risk reduction for dementia and a 32% risk reduction for Alzheimer’s disease.

Update 2. Statins significantly reduce CV events in patients with hypertriglyceridemia

Statins significantly reduce CV events in patients with hypertriglyceridemia²

In “Beyond cholesterol: triglycerides as the new frontier in cardiac prevention,” Michael Shapiro (Winston-Salem, NC) reported that triglyceride-rich lipoproteins (TGRL) have four-fold higher cholesterol content than low-density lipoprotein (LDL) particles and have higher atherogenicity per particle.² Plasma triglyceride (TG) levels predict cardiovascular (CV) and total mortality.² Vera Bittner (Birmingham, AL) reported that statins reduce atherosclerotic CV disease (ASCVD) events in patients with hypertriglyceridemia.³

Update 3. Genetically confirmed FH predicts increased benefit from statins

Patients with genotypically confirmed FH obtain markedly greater benefit from statin therapy⁴

In the “Annual lipidology update,” Pradeep Natarajan (Boston, MA) presented data showing that patients with genotypically confirmed familial hypercholesterolemia (FH) obtain markedly greater benefit from statin therapy.⁴

Update 4. Statins are underutilized in T2DM

35% of patients with T2DM do not receive a statin⁵

In the “Robert Levy memorial lecture and lifestyle and cardiometabolic health early career investigator award competition,” Emily Decicco (Dallas, TX) described a real-world study of statin use for primary prevention of ASCVD in patients with type 2 diabetes mellitus (T2DM).⁵ Of 241,232 patients across 90 US health systems, 35% were not receiving any statin therapy.

Higher statin doses improve LDL-C control

Dr. Decicco added that LDL cholesterol (LDL-C) control was suboptimal in the overall population, but it improved with moderate-to-high-intensity statin therapy.⁵ Statin use was higher in patients with risk enhancers such as neuropathy, retinopathy, and chronic kidney disease. Younger patients and women were at increased risk of undertreatment.

LDL -C levels were lowest in patients receiving moderate-to-high-intensity statin therapy⁵

Update 5. CAC scoring can help identify patients who will benefit from statin therapy

Statins reduce ASCVD events in patients with CAC scores >100⁷

In “Coronary imaging in prevention trials: past, present, and future,” Anurag Mehta (Richmond, VA) presented a case of a 63-year-old African American man with hypertension and mildly elevated cholesterol and creatinine receiving amlodipine 10 mg and hydrochlorothiazide 25 mg daily.⁶ His estimated 10-year ASCVD risk was 16%.⁶ Tamar Polonsky (Chicago, IL) noted that coronary artery calcium (CAC) testing would be reasonable for this patient, and is recommended in the 2018 AHA/American College of Cardiology (ACC) guidelines for patients with a 10-year ASCVD risk of 5–20% if the decision about statin therapy is uncertain.⁷ Dr. Polonsky added that statins reduce ASCVD events in patients with CAC scores >100.⁷

Use of CAC beyond current risk predictors

In “Understanding cardiovascular risk: from assessment to implementation,” Seamus Whelton (Lutherville, MA) remarked that higher CAC is strongly associated with ASCVD risk.⁸ CAC >0 uncovers high risk in patients who would be considered at low or intermediate risk by the Pooled Cohort Equations.⁸

Update 6. Polygenic risk scores identify patients who obtain the greatest benefit from statins

PRS can identify individuals likely to obtain the greatest benefit from statins⁹

In “Polygenic risk scores for cardiovascular disease – opportunities and challenges for clinical implementation,” Dr. Natarajan reported that polygenic risk scores (PRS) for coronary artery disease (CAD) can identify individuals who are likely to obtain the greatest benefit from statins.⁹ Sadiya Khan (Chicago, IL), however, remarked that the risk for coronary heart disease is explained by well-established risk factors, and PRS have limited additive utility in the general population when added to multivariable risk scores.¹⁰

Update 7. Central role of LDL-C reduction in prevention of ASCVD emphasized

Greater reduction of LDL-C leads to greater reduction of ASCVD¹¹

In “Understanding cardiovascular risk: from assessment to implementation,” Ian Graham (Dublin, Ireland) emphasized that Mendelian randomization studies, prospective cohort studies, and controlled clinical trials have clearly demonstrated the crucial role of LDL-C reduction for the prevention of ASCVD.¹¹ He suggested that 10-year risk could be replaced by exposure time to LDL-C.

Martha Gulati (Los Angeles, CA) described how risk enhancers can be implemented into risk assessment.¹² Important risk enhancers include a CAC score >0, ankle−brachial index ≤0.9, and lipoprotein (a) (Lp[a]) ≥50 nmol/L. These factors can inform the decision to intensify statin therapy.¹²

Update 8. VERVE-101 produces prolonged reduction in LDL-C

VERVE -101 reduces LDL-C for up to 180 days¹³

In “Late-breaking science: future of lipid lowering therapy – novel mechanisms and approaches,” Andrew Bellinger (Cambridge, MA) reported interim results of the Phase Ib heart-1 trial of VERVE-101, a novel clustered regularly interspaced short palindromic repeats (CRISPR) base editing medicine designed to inactivate hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) and lower LDL-C.¹³ Single infusions of VERVE-101 for patients with severe, advanced ASCVD produced durable dose-dependent reductions in LDL-C, and the safety profile supported continued development.

Update 9. Fibrates significantly reduce ASCVD in patients with high TGs/low HDL-C

Fibrates reduce ASCVD events in patients with high TGs and/or low HDL-C³

In “Beyond cholesterol: triglycerides as the new frontier in cardiac prevention,” Vera Bittner remarked that fibrates including fenofibrate have been reported to reduce ASCVD events in patients with high TGs and/or low high-density lipoprotein cholesterol (HDL-C) levels.³

Approved treatments to reduce TGRL include fenofibrate

In the “Annual lipidology update,” Lale Tokgozoglu (Ankara, Turkey) remarked that fenofibrate is recommended in European guidelines for patients with TG levels >200 mg/dL, while icosapent ethyl is recommended in European guidelines and the ACC Consensus Paper on hypertriglyceridemia. Agents under development to reduce TGs include apolipoprotein C3 inhibitors and angiopoietin-like protein 3 inhibitors.¹⁴

Plozasiran shows potent TG reduction

In “Targeting lipid lowering via novel pathways,” Daniel Gaudet (Montreal, Canada) presented the Phase IIb SHASTA-2 study of plozasiran, an investigational RNA interference (RNAi) therapeutic, in patients with severe hypertriglyceridemia.¹⁵ More than 90% of subjects treated with plozasiran 50 mg (given by injection at Weeks 0 and 12) achieved TG levels <500 mg/dL at Week 24.

Update 10. New PROMINENT results suggest benefit of fibrates on microvascular disease

PROMINENT: Pemafibrate reduced ischemic ulcer or gangrene¹⁶

In “Featured science from artery to veins: a fantastic journey,” Aruna Pradhan (New York, USA) presented new data from the PROMINENT trial of pemafibrate in patients with T2DM and mixed dyslipidemia.¹⁶ Compared with placebo, pemafibrate significantly reduced the risk of lower extremity ischemic ulceration or gangrene. These results suggest a potential benefit of fibrates on microvascular disease.

Update 11. Large Lp(a) reductions may be needed to reduce ASCVD risk

Large Lp(a) reductions may be needed to reduce ASCVD risk¹⁷

In “Targeting lipid lowering via novel pathways,” Michelle O’Donoghue (Boston, MA) explained that ASCVD risk persists despite reduction of LDL-C even to <20 mg/dL; this necessitates additional strategies beyond LDL-C reduction.¹⁷ Lp(a) plays a significant role in ASCVD, but genetic studies suggest that a large reduction in Lp(a) would be needed to produce clinical benefits.

New Lp(a)-lowering therapies are under investigation

In “Lp(a) and ASCVD: a quiet epidemic?” Dr. O’Donoghue described agents under investigation for the reduction of Lp(a).¹⁸ These include the small interfering RNAs olpasiran, zerlasiran, and lepodisiran; the small molecule inhibitor muvalaplin; and the antisense oligonucleotide pelacarsen, which have demonstrated large reductions in Lp(a) in early studies.

Update 12. New risk equations predict ASCVD, total CVD, and HF

The AHA PREVENT^TM equations estimate risk of ASCVD, total CVD, and HF¹⁹

In “A confluence of risk: navigating the intersection of cardiovascular, kidney and metabolic health,” Dr. Khan presented the AHA Predicting Risk of Cardiovascular Disease Events (AHA PREVENT^TM) equations.¹⁹ AHA PREVENT^TM was designed to estimate the risk of ASCVD, total CV disease (CVD), and heart failure (HF) over 10 years and 30 years. Traditional risk factors included in the equations were smoking status, systolic blood pressure, non-HDL-C, antihypertensive therapy, lipid-lowering therapy, and estimated glomerular filtration rate. Body mass index, urinary albumin:creatinine ratio, glycated hemoglobin (HbA1c), and social deprivation index could also be added. The score was derived using data from 25 datasets containing >3 million individuals and validated from 21 datasets also containing >3 million individuals. For all three outcomes, the c-statistics ranged from 0.74 to 0.83, and the calibration slope for observed vs predicted outcomes was between 0.89 and 1.09.

Lipitor^® (Atorvastatin Calcium) Has an Established Safety Profile¹

Lipitor^® 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 Lipitor^® discontinued due to adverse reactions compared to 4.0% of patients on placebo.

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

As with other HMG-CoA reductase inhibitors elevated serum transaminases have been reported in patients receiving Lipitor^®. Clinically important (> 3 times upper normal limit) elevations in serum transaminases occurred in 0.7% patients on Lipitor^®. These elevations were dose related and were reversible in all patients.¹

Paediatric population¹

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.¹

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.¹

Lipitor^® (Atorvastatin Calcium) Has A Proven Safety Profile Across the Dose Range

Data from a pooled analysis involving 14 236 patients from 49 trials^*2

*Based on the number of patients with laboratory measurements

High- Intensity Lipitor^® (Atorvastatin Calcium) Has A Comparable Safety Profile as Moderate Intensity Lipitor^® in High-Risk and Elderly Patients^3,4

In TNT, a 5-year study of >10000 patients with CHD³

In patients with CHD and type 2 diabetes – as seen in a subgroup analysis of TNT⁴

In multiple clinical trials no overall differences in safety have been observed in patients aged ≥65 years and ≥75 years vs younger patients^1†

*Persistent ALT/AST elevations were 2 consecutive measurements obtained 4-10 days apart that were >3x ULN.³

Greater sensitivity of some older adults cannot be ruled out. As advanced age (≥65 years) is a predisposing factor for myopathy atorvastatin should be prescribed with caution in the elderly¹

An Established Safety Profile Across the Dose Range with Lipitor^® (Atorvastatin Calcium)

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.^5-7

ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; CK: Creatinine Kinase; CHD: Coronary Heart Disease; TNT: Treat to New Target Trial

LIPITOR^® Abbreviated Product Information

Presentation: Lipitor (Crystalline Atorvastatin) Film Coated Tablet available in blister tab: 10mg x 30’s. 20mg x 30’s. 40mg x 30’s. 80mg x 30’s. Indication: Lipitor (Crystalline Atorvastatin) is indicated as an adjunct to diet for the treatment of patients with elevated total cholesterol, LDL cholesterol, apolipoprotein B & triglycerides & to increase HDL-cholesterol in patients with primary hypercholesterolaemia (heterozygous familial & non-familial hypercholesterolaemia), combined (mixed) hyperlipidaemia (Fredrickson types lla & llb), elevated serum triglyceride levels (Fredrickson type IV), and for patients with dysbetalipoproteinaemia (Fredrickson type lll) who do not respond adequately to diet. Reduction of total & LDL-cholesterol in patients with homozygous familial hypercholesterolaemia. Reduction of total & LDL cholesterol & apolipoprotein B levels in boys & postmenarchal girls, 10-17 yr, with heterozygous familial hypercholesterolemia when after adequate diet therapy, LDL cholesterol remains ≥190 mg/dL or ≥160 mg/dL & there is a positive family history of premature CV disease or 2 or more other CV disease risk factors. For prevention of CV disease without clinically evident coronary heart disease but with multiple risk factors e.g. age, smoking, HTN, low HDL-C, or family history of early coronary heart disease, Lipitor is indicated to reduce the risk of MI, stroke & revascularisation procedures & angina. In type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors e.g. retinopathy, albuminuria, smoking or HTN, Lipitor is indicated to reduce the risk of MI & stroke. In patients with clinically evident CHD, Lipitor is indicated to reduce the risk of non-fatal MI, fatal & non-fatal stroke, revascularisation procedures, hospitalisation for CHF & angina. Dosing: Dose range: 10mg-80 mg once daily. Doses may be given any time of the day with or without food. Starting & maintenance dose should be individualised according to baseline LDL-cholesterol levels, the goal of therapy & patient response. Contraindication: Hypersensitivity to any component of this medication, Active liver disease or elevated serum transaminases >3 times the upper limit of normal. Pregnancy, lactation or of childbearing potential who are not on adequate contraceptive measures. Special Precaution: Hepatic effects and Skeletal Muscle Effects including Immune-Mediated Necrotizing Myopathy (IMNM); monitor for creatine phosphokinase & transaminases elevations; haemorrhagic stroke; endocrine dysfunction. Concurrent administration of fibric acid derivatives, erythromycin, immunosuppressive drugs, azole antifungals, HIV/HCV protease inhibitors, HCV NS5A/NS5B inhibitors, letermovir or lipid-modifying doses of niacin (≥1g/day); lowest dose necessary of atorvastatin should be employed. The concurrent use of atorvastatin and fusidic acid is not recommended. Avoid alcohol consumption. Adverse Reaction: nasopharyngitis, hyperglycemia, pharyngolaryngeal pain, epistaxis, diarrhea, dyspepsia, nausea, flatulence, arthralgia, pain in extremity, musculoskeletal pain, muscle spasms, myalgia, joint swelling, liver function test abnormal, blood creatine phosphokinase increased.

API-LIPITOR-1023

Full prescribing information is available upon request.