Stakeholder Insight: Dyslipidemia - Titration versus Combination Therapy

Table of Contents

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the dyslipidemia market

Summary

Key metrics

CHAPTER 2 INTRODUCTION AND SCOPE

Coverage of the Stakeholder Insight Survey

CHAPTER 3 COUNTRY TREATMENT TREES

Introduction to the treatment trees

US

Japan

France

Germany

Italy

Spain

UK

CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION

Disease definition and classification

Definition of dyslipidemia

NCEP treatment guidelines

Epidemiology of dyslipidemia

US

Japan

France

Germany

Italy

Spain

UK

Key patient segmentations

Segmentation by type of dyslipidemia

Familial hypercholesterolemia

Low HDL cholesterol

Segmentation by disease severity

Co-morbidities and risk factors

Compliance among patients taking concomitant therapy

Dyslipidemia patients with obesity

Dyslipidemia patients with type 2 diabetes

CHAPTER 5 DIAGNOSIS AND TREATMENT RATES

Diagnosis rates

Who manages dyslipidemia?

Treatment options

Overview of treatment rates

Comparison of treatment rates for dyslipidemia sub-populations

CHAPTER 6 OVERALL PRESCRIBING TRENDS

Prescribing trends

Statin use in different dyslipidemia populations

Fibrate use in different dyslipidemia populations

Nicotinic acid derivative use in different dyslipidemia populations

Bile acid sequestrant use in different dyslipidemia populations

Fish oil derivative use in different dyslipidemia populations

Ezetimibe use in different dyslipidemia populations

Advicor use in different dyslipidemia populations

CHAPTER 7 ANALYSIS OF STATIN THERAPY

Trends in statin therapy

Breakdown of statin prescribing by type of statin

Breakdown of statin prescribing by line of therapy

Breakdown of statin prescribing by daily dose

Brand versus generic statin prescribing: current and future trends

Limitations of statin therapy

CHAPTER 8 ANALYSIS OF FIBRATE THERAPY

Trends in fibrate therapy

Breakdown of statin prescribing by type of statin

Changes in fibrate usage over recent years

CHAPTER 9 FIRST TO SECOND LINE THERAPY

First line therapy

Breakdown of first line therapy by drug class

Breakdown of statins by compound at first line

Second line therapy

Patients progressing to second line therapy

Breakdown of second line therapy by drug class

Patients progressing to third line therapy and beyond

Changes in anti-dyslipidemic therapy

Patients having their drug therapy changed

Reasons for changes in therapy

Types of therapy changes

CHAPTER 10 ANALYSIS OF COMBINATION THERAPY

Current and future prescribing of combination therapy

Proportion of patients receiving combination therapy

Future prescribing of combination therapy

Breakdown of combination therapy

Statin + fibrate combination

Statin + nicotinic acid derivative combination

Statin + bile acid sequestrant combination

Statin + fish oil derivative combination

Statin + ezetimibe combination

Non-statin combinations

Factors influencing future use of new adjunctive therapies

Incentives to prescribe adjunctive therapies

Disincentives to prescribe adjunctive therapies

CHAPTER 11 IMPROVING TREATMENT OUTCOMES

Treatment outcomes

Patients failing to achieve target cholesterol goals

Factors influencing the prescribing of anti-dyslipidemics

CHAPTER 12 OTHER STAKEHOLDER INFLUENCES

Regulatory perspectives: From approval to post-marketing

Delays in approval of new statins

Post-marketing surveillance of adverse events

Payer/provider perspectives: Cost and reimbursement

The cost and reimbursement of Crestor

The cost and reimbursement of Zetia

Pricing of statins in Japan: the entry price of Livalo

Pharmacist perspectives: Switching statins to OTC status

OTC statins: developments in the US and UK

Patient perspectives: DTC advertising and consumer groups

The role of DTC advertising on patient demand

Increasing patient awareness through the media

CHAPTER 13 OPINION LEADER TRANSCRIPTS

Prof Paul Durrington

Diagnosis and treatment

Statin therapy

Fibrate therapy

Combination therapy

Single pill combination therapies

Cross-risk factor single pill combination therapies

Treatment of diabetic dyslipidemia

Uptake of new therapies: Zetia (ezetimibe) and Crestor (rosuvastatin)

Dr Tony Wierzbicki, UK

Diagnosis and treatment

Statin therapy

Fibrate therapy

Combination therapy

Single pill combination therapies

Cross-risk factor single pill combination therapies

Treatment of diabetic dyslipidemia

Uptake of new therapies: Zetia (ezetimibe) and Crestor (rosuvastatin)

Prof Dan Atar

Diagnosis and treatment

Statin therapy

Fibrate therapy

Combination therapy

Single pill combination therapies

Cross-risk factor single pill combination therapies

Treatment of diabetic dyslipidemia

Uptake of new therapies: Zetia (ezetimibe) and Crestor (rosuvastatin)

Dr Robert S. Rosenson

Diagnosis and treatment

Statin therapy

Fibrate therapy

Combination therapy

Single pill combination therapies

Cross-risk factor single pill combination therapies

Treatment of diabetic dyslipidemia

Uptake of new therapies: Zetia (ezetimibe) and Crestor (rosuvastatin)

Bibliography

General and clinical trial data

Epidemiology sources

US

Japan

France

Germany

Italy

Spain

UK

Pricing sources

Physician research methodology

Physician Sample breakdown

Physician questionnaire

Disclaimer

List of Tables

Table 1: Prevalence of total cholesterol >200mg/dL in the seven major markets (000s), 2003-2011

Table 2: Key changes to lipid levels between the NCEP II and NCEP III guidelines

Table 3: Prevalence of total cholesterol >200mg/dL in the seven major markets (000s), 2003-2011

Table 4: Prevalence of low HDL cholesterol (<40mg/dL) in England in 1998

Table 5: Estimated proportion of dyslipidemia patients with co-morbid conditions and risk factors in the seven major markets, 2003

Table 6: Framingham Heart Study data on lipid levels in men and women with and without diabetes

Table 7: Mean plasma lipid levels at diagnosis of type 2 diabetes in the UKPDS

Table 8: Estimated breakdown of the management of dyslipidemia in the general population by physician type, 2003

Table 9: Major characteristics of the key anti-dyslipidemic drug classes, 2003

Table 10: Breakdown of dyslipidemia management across the different populations in the seven major markets, 2003

Table 11: Proportion of drug-treated patients prescribed each type of therapy in the seven major markets, 2003

Table 12: Changes in statin prescribing and annual spending in the UK from 2000 to 2003

Table 13: Primary and secondary CHD prevention trials with statins in diabetic patients

Table 14: Comparison of ezetimibe use with other adjunctive drug classes in the US, Germany and the UK, 2003

Table 15: Factors influencing the uptake of ezetimibe, 2003

Table 16: Comparison of annual cost of Advicor versus generic lovastatin + Niaspan ER, 2003

Table 17: ADVOCATE trial results

Table 18: Number of physicians prescribing rosuvastatin in Germany and the UK, 2003

Table 19: Extent to which physicians agree or disagree that rosuvastatin will become the most prescribed statin within the next five years, 2003

Table 20: Extent to which physicians agree or disagree that they will be cautious in prescribing Crestor as the safety profile of this drug is unproven, 2003

Table 21: Extent to which the physicians agree or disagree that Crestor has HDL cholesterol raising benefits over other statins, which will encourage them to prescribe it, 2003

Table 22: Comparison of US drug prices for Lipitor and Crestor, 2003

Table 23: Extent to which the physicians agree or disagree that the lack of long-term mortality and morbidity data for Crestor will limit their prescribing of Crestor, 2003

Table 24: Sample of physician responses for change in choice of statin for diabetic dyslipidemics, 2003

Table 25: Breakdown of statin prescribing by line of therapy in the seven major markets, 2003

Table 26: Statin doses available in the seven major markets, 2003

Table 27: Breakdown of statin prescribing by daily dose in the seven major markets, 2003

Table 28: Proportion of drug-treated dyslipidemia patients prescribed each anti-dyslipidemic drug class as first line therapy in the seven major markets, 2003

Table 29: Extent to which physicians agree or disagree that they would only prescribe Crestor at first line in patients requiring a substantial reduction in LDL cholesterol, 2003

Table 30: Proportion of drug-treated dyslipidemia patients prescribed each anti-dyslipidemic drug class as second line therapy in the seven major markets, 2003

Table 31: Average number of changes a patient undergoes over one year, 2003

Table 32: Average number of patient therapy change opportunities over one year in the seven major markets, 2003

Table 33: Number and frequency of rhabdomyolysis cases for all the statins in the US from launch to May 2001

Table 34: Factors driving versus factors limiting the use of combination therapy in the treatment of dyslipidemia, 2003

Table 35: Change in combination therapy over the next three years in the seven major markets, 2003

Table 36: Breakdown of combination therapy by dyslipidemia sub-population in the seven major markets, 2003

Table 37: Overview of clinical trials assessing statin-fibrate combinations, 2003

Table 38: LDL cholesterol reductions with colesevelam alone and in combination

Table 39: Trial results for ezetimibe in combination with simvastatin

Table 40: Comparison of efficacy of ezetimibe in combination with simvastatin, atorvastatin, lovastatin and pravastatin

Table 41: Physician ratings of factors providing incentives for the future prescribing of new therapies as adjuncts to statins in the seven major markets, 2003

Table 42: Physician ratings of factors providing disincentives for the future prescribing of new therapies as adjuncts to statins in the seven major markets, 2003

Table 43: Proportion of drug-treated dyslipidemia patients in each sub-population failing to reach target cholesterol goals in the seven major markets, 2003

Table 44: Average rating of factors influencing the prescribing of anti-dyslipidemic therapy in the seven major markets, 2003

Table 45: Comparison of annual cost of therapy in the US of Zetia, WelChol and Niaspan, 2003

Table 46: Attempted OTC switching

Table 47: Issues related to the availability of OTC statins, 2003

Table 48: Ranking of factors influencing the prescribing of anti-dyslipidemic therapy

Table 49: Ranking of factors influencing the prescribing of anti-dyslipidemic therapy

Table 50: Ranking of factors influencing the prescribing of anti-dyslipidemic therapy

Table 51: Ranking of factors influencing the prescribing of anti-dyslipidemic therapy

Table 52: US physician sample breakdown, 2003

Table 53: Japan physician sample breakdown, 2003

Table 54: France physician sample breakdown, 2003

Table 55: Germany physician sample breakdown, 200

Table 56: Italy physician sample breakdown, 200

Table 57: Spain physician sample breakdown, 2003

Table 58: UK physician sample breakdown, 2003

Table 59: Risk factors and co-morbidities

Table 60: Breakdown by type of dyslipidemia

Table 61: Breakdown of dyslipidemia by disease severity

Table 62: Management of dyslipidemia by physician type

Table 63: Breakdown of treatment by lifestyle advice versus drug therapy

Table 64: Breakdown of drug therapy by anti-dyslipidemic class

Table 65: Breakdown of statin use by compound

Table 66: Breakdown of statin use by line of therapy

Table 67: Breakdown of statin use by daily dose

Table 68: Current branded versus generic statin prescribing

Table 69: Future branded versus generic prescribing

Table 70: Breakdown of fibrate use by compound

Table 71: Breakdown of first line therapy by anti-dyslipidemic drug class

Table 72: Breakdown of statin use at first line by compound

Table 73: Reasons for changes in anti-dyslipidemic therapy

Table 74: Types of changes in anti-dyslipidemic therapy

Table 75: Breakdown of second line therapy by anti-dyslipidemic drug class

Table 76: Proportion of patients receiving combination therapy

Table 77: Expected change in prescribing of combination therapy over the next three years

Table 78: Breakdown of combination therapy

Table 79: Advicor versus prescribing of two separate pills

Table 80: Patients failing to achieve target cholesterol goals

Table 81: Rating of factors influencing the prescribing of anti-dyslipidemic therapy

Table 82: Rating of factors influencing use of new therapies as adjuncts to statins

Table 83: Order of statin preference for use with ezetimibe

Table 84: Statement regarding Crestor

Table 85: Breakdown of patients receiving Crestor after first year on the market

List of Figures

Figure 1: Scope and coverage of Datamonitor�fs 2003 dyslipidemia reports

Figure 2: Key drivers of the dyslipidemia market to 2011

Figure 3: Overview of diagnosis rates, treatment rates and prescribing trends in the seven major markets, 2003

Figure 4: Diagrammatic overview of the coverage of the dyslipidemia Stakeholder Insight survey, 2003

Figure 5: Breakdown of the overall dyslipidemia population in the US by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 6: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in the US, 2003

Figure 7: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in the US, 2003

Figure 8: Breakdown of first and second line therapy by anti-dyslipidemic drug class in the US, 2003

Figure 9: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in the US, 2003

Figure 10: Breakdown of combination therapy by dyslipidemia sub-population in the US, 2003

Figure 11: Breakdown of treatment outcomes by dyslipidemia sub-population in the US, 2003

Figure 12: Physician awareness and perception of ezetimibe and rosuvastatin in the US in June/July 2003

Figure 13: Breakdown of the overall dyslipidemia population in Japan by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 14: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in Japan, 2003

Figure 15: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in Japan, 2003

Figure 16: Breakdown of first and second line therapy by anti-dyslipidemic drug class in Japan, 2003

Figure 17: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in Japan, 2003

Figure 18: Breakdown of combination therapy by dyslipidemia sub-population in Japan, 2003

Figure 19: Breakdown of treatment outcomes by dyslipidemia sub-population in Japan, 2003

Figure 20: Physician awareness and perception of ezetimibe and rosuvastatin in Japan in June/July 2003

Figure 21: Breakdown of the overall dyslipidemia population in France by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 22: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in France, 2003

Figure 23: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in France, 2003

Figure 24: Breakdown of first and second line therapy by anti-dyslipidemic drug class in France, 2003

Figure 25: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in France, 2003

Figure 26: Breakdown of combination therapy by dyslipidemia sub-population in France, 2003

Figure 27: Breakdown of treatment outcomes by dyslipidemia sub-population in France, 2003

Figure 28: Physician awareness and perception of ezetimibe and rosuvastatin in France in June/July 2003

Figure 29: Breakdown of the overall dyslipidemia population in Germany by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 30: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in Germany, 2003

Figure 31: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in Germany, 2003

Figure 32: Breakdown of first and second line therapy by anti-dyslipidemic drug class in Germany, 2003

Figure 33: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in Germany, 2003

Figure 34: Breakdown of combination therapy by dyslipidemia sub-population in Germany, 2003

Figure 35: Breakdown of treatment outcomes by dyslipidemia sub-population in Germany, 2003

Figure 36: Physician awareness and perception of ezetimibe and rosuvastatin in Germany in June/July 2003

Figure 37: Breakdown of the overall dyslipidemia population in Italy by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 38: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in Italy, 2003

Figure 39: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in Italy, 2003

Figure 40: Breakdown of first and second line therapy by anti-dyslipidemic drug class in Italy, 2003

Figure 41: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in Italy, 2003

Figure 42: Breakdown of combination therapy by dyslipidemia sub-population in Italy, 2003

Figure 43: Breakdown of treatment outcomes by dyslipidemia sub-population in Italy, 2003

Figure 44: Physician awareness and perception of ezetimibe and rosuvastatin in Italy in June/July 2003

Figure 45: Breakdown of the overall dyslipidemia population in Spain by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 46: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in Spain, 2003

Figure 47: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in Spain, 2003

Figure 48: Breakdown of first and second line therapy by anti-dyslipidemic drug class in Spain, 2003

Figure 49: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in Spain, 2003

Figure 50: Breakdown of combination therapy by dyslipidemia sub-population in Spain, 2003

Figure 51: Breakdown of treatment outcomes by dyslipidemia sub-population in Spain, 2003

Figure 52: Physician awareness and perception of ezetimibe and rosuvastatin in Spain in June/July 2003

Figure 53: Breakdown of the overall dyslipidemia population in the UK by diagnosis, type of dyslipidemia, disease severity and prevalence of risk factors and co-morbidities, 2003

Figure 54: Breakdown of drug therapy in the diagnosed dyslipidemia sub-populations in the UK, 2003

Figure 55: Breakdown of statin therapy by compound, line of therapy, daily dose and use of brands versus generics in the UK, 2003

Figure 56: Breakdown of first and second line therapy by anti-dyslipidemic drug class in the UK, 2003

Figure 57: Segmentation of drug-treated overall dyslipidemia population having therapy changed over a one year period in the UK, 2003

Figure 58: Breakdown of combination therapy by dyslipidemia sub-population in the UK, 2003

Figure 59: Breakdown of treatment outcomes by dyslipidemia sub-population in the UK, 2003

Figure 60: Physician awareness and perception of ezetimibe and rosuvastatin in the UK in June/July 2003

Figure 61: Proportion of diagnosed dyslipidemia patients with each type of dyslipidemia in the seven major markets, 2003

Figure 62: Proportion of diagnosed hypercholesterolemia patients with familial hypercholesterolemia in the seven major markets, 2003

Figure 63: Proportion of diagnosed dyslipidemia patients with low HDL cholesterol in the seven major markets, 2003

Figure 64: Breakdown of the diagnosed dyslipidemia population by disease severity in the seven major markets, 2003

Figure 65: US age-adjusted prevalence of obese and overweight adults

Figure 66: Estimated proportion of dyslipidemia patients in the general population diagnosed in the seven major markets, 2003

Figure 67: A model of steps in Therapeutic Lifestyle Changes (TLC) from the ATP III guidelines

Figure 68: Combined seven country breakdown of dyslipidemia management by population, 2003

Figure 69: Proportion of dyslipidemia patients in each sub-population prescribed statins across the seven major markets, 2003

Figure 70: Proportion of dyslipidemia patients in each sub-population prescribed fibrates across the seven major markets, 2003

Figure 71: Proportion of dyslipidemia patients in each sub-population prescribed nicotinic acid derivatives across the seven major markets, 2003

Figure 72: Proportion of dyslipidemia patients in each sub-population prescribed bile acid sequestrants across the seven major markets, 2003

Figure 73: Proportion of dyslipidemia patients in each sub-population prescribed fish oil derivatives across the seven major markets, 2003

Figure 74: Proportion of dyslipidemia patients in each sub-population in the US, Germany and the UK prescribed ezetimibe, 2003

Figure 75: Awareness of ezetimibe across the seven major markets, 2003

Figure 76: Proportion of overall drug-treated dyslipidemia patients expected to be prescribed ezetimibe by the end of its first year on the market in the seven major markets

Figure 77: The statin �erule of six�f

Figure 78: Proportion of dyslipidemia patients in each sub-population prescribed Advicor in the US, 2003

Figure 79: Breakdown of statin prescribing by type of statin in overall dyslipidemia patients in the seven major markets, 2003

Figure 80: Awareness of rosuvastatin across the seven major markets, June/July 2003

Figure 81: Proportion of overall drug-treated dyslipidemia patients expected to be prescribed rosuvastatin by the end of its first year on the market in the seven major markets

Figure 82: Anticipated prescribing of rosuvastatin in newly diagnosed versus poorly controlled patients by the end of its first year on the market

Figure 84: Availability of generic statins in the seven major markets, 2003

Figure 85: Current and future brand versus generic prescribing of statins in the US

Figure 86: Current and future brand versus generic prescribing of statins in Japan

Figure 87: Current and future brand versus generic prescribing of statins in France

Figure 88: Current and future brand versus generic prescribing of statins in Germany

Figure 89: Current and future brand versus generic prescribing of statins in Italy

Figure 90: Current and future brand versus generic prescribing of statins in Spain

Figure 91: Current and future brand versus generic prescribing of statins in the UK

Figure 92: Proportion of drug-treated dyslipidemia patients unable to tolerate statin therapy in the seven major markets, 2003

Figure 93: Proportion of drug-treated dyslipidemia patients refusing to take statin therapy in the seven major markets, 2003

Figure 94: Proportion of dyslipidemia patients on statin therapy that are refractory to statins in the seven major markets, 2003

Figure 95: Breakdown of fibrate prescribing by compound in overall dyslipidemia patients in the seven major markets, 2003

Figure 96: Proportion of dyslipidemia patients receiving statins at first line prescribed each compound in the seven major markets, 2003

Figure 97: Proportion of drug-treated dyslipidemia patients progressing to second line therapy, 2003

Figure 98: Comparison of anti-dyslipidemic drug classes at first versus second line in the combined seven markets, 2003

Figure 99: Proportion of drug-treated dyslipidemia patients on second line therapy progressing to third line therapy and beyond, 2003

Figure 100: Proportion of drug-treated dyslipidemia patients having their therapy changed over a one year period, 2003

Figure 101: Reasons for change in anti-dyslipidemic therapy in the seven major markets, 2003

Figure 102: Type of changes in anti-dyslipidemic therapy in the seven major markets, 2002

Figure 103: Proportion of drug-treated dyslipidemia patients in each sub-population receiving combination therapy in the seven major markets, 2003

Figure 104: Proportion of overall drug-treated dyslipidemia patients in each sub-population receiving a statin + fibrate combination in the seven major markets, 2003

Figure 105: Proportion of overall drug-treated dyslipidemia patients in each sub-population receiving a statin + nicotinic acid derivative combination in the seven major markets, 2003

Figure 106: Breakdown of statin + nicotinic acid derivative combination by Advicor versus two separate pills in the US, 2003

Figure 107: Proportion of overall drug-treated dyslipidemia patients in each sub-population receiving a statin + bile acid sequestrant combination in the seven major markets, 2003

Figure 108: Proportion of overall drug-treated dyslipidemia patients in each sub-population receiving a statin + fish oil derivative combination in the seven major markets, 2003

Figure 109: Proportion of overall drug-treated dyslipidemia patients in each sub-population receiving a statin + ezetimibe combination, 2003

Figure 110: Physician rating of the order of statin preference for use in combination with ezetimibe, 2003

Figure 111: Proportion of overall drug-treated dyslipidemia patients in each sub-population receiving a non-statin combination, 2003

Figure 112: Average ratings across the seven major markets for the incentives versus the disincentives to prescribing, 2003

Figure 113: Proportion of drug-treated familial hypercholesterolemia patients failing to reach target cholesterol goals in the seven major markets, 2003

Figure 114: Opinion leader ranking of clinical unmet needs in the dyslipidemia market, 2003