This market analysis provides a comprehensive examination of key cardiovascular therapy areas: atherosclerosis; cholesterol, lipids and triglycerides; hypertension, coronary heart disease and heart failure; pulmonary arterial hypertension; atrial fibrillation and thrombosis. The report includes unique sales forecasts for new and current products, as well as critical anlayses and competitive ratings for upcoming products.

Cardiovascular disease is a global problem. In the developed world, its prevalence is linked to our increasingly unhealthy lifestyle, with risk factors including lack of exercise, overweight and obesity, and smoking. These are also linked to diabetes which greatly increases the risk of developing heart disease.

The cardiovascular market contains a number of blockbusting drugs, including the world's largest selling drug, Pfizer's Lipitor (atorvastatin), with sales of US$12.2 billion in 2005. Sales of the 20 biggest selling branded drugs in 2005 amounted to US$54.5 billion from a total market of around US$75 billion, based on reported sales figures.

But what of the future? Opportunities for new therapies exist in both main and niche markets - the latter being relatively uncompetitive and where there is high unmet clinical need, such as pulmonary arterial hypertension.

This report provides a detailed insight into the current and future market for cardiovascular drugs.

- It provides an overview of the marketplace, outlining morbidity and mortality around the world and summarising the leading drugs in terms of sales and US patent expiry.
- It examines drug development among major pharmaceutical companies, covering both novel drugs and launched products in development as part of their life cycle management programmes.
- For each therapy section the major treatments are discussed in depth, including sales forecasts to 2011 for leading drugs. In addition, a number of new and future treatments have been identified and analysed in order to assess their future market potential.

Appendices provide insight into leading cardiovascular markets in terms of morbidity, mortality, drug consumption and the cost of treatment where available, for the USA, Japan, France, Germany, the UK, Italy, Spain and Canada.

Unique competitor/product evaluation
A key feature of this report is the unique assessment made of products and companies that evaluates not only their pharmacological profile and clinical benefits, but also assesses their chances of reaching the market.

For a number of new and future drugs, Espicom has provided a competitor ratio analysis, based on our assessment of five criteria:

- Novelty/rational for mechanism of action;
- Proof of concept/clinical data;
- Management/clinical expertise;
- Competition with the marketplace;
- Risks associated with drug development in therapeutic class.

Each of these criteria attracts a maximum of ten points, resulting in a maximum score of 50 overall. Each of the drugs included is discussed in more detail in the relevant section of this report. ATHEROSCLEROSIS
Atherosclerosis is a progressive disease of the arteries, during which deposits of fatty substances, cholesterol, cellular waste products, calcium and other substances collectively known as plaque build up in the inner lining of
an artery. Atherosclerosis is the leading underlying cause
of death from heart attack and stroke and accounts for nearly 75% of all deaths from cardiovascular disease.

Risk factors associated with atherosclerosis include: elevated LDL-cholesterol and triglyceride levels, hypertension, diabetes mellitus, smoking, obesity and physical inactivity. As yet, there are no medications available for the direct treatment of the underlying chronic inflammation of atherosclerosis. Current treatments are aimed at reducing LDL-cholesterol to reduce the risk of heart disease, or decreasing platelet aggregation in the case of atherothrombosis.

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CHOLESTEROL, LIPIDS AND TRIGLYCERIDES
Cholesterol and triglyceride management significantly reduces the risk of heart disease.

Statins are commonly used as first line therapy to lower LDL-cholesterol and triglycerides. The most frequently prescribed of the five statins currently available in the USA and EU is Pfizer's Lipitor (atorvastatin), with global sales of US$12.2 billion in 2005. The newest statin to reach the market is AstraZeneca's Crestor (rosuvastatin), which was approved by the US FDA in 2003. Rosuvastatin is the first statin to demonstrate regression of atherosclerosis in clinical trials.

Combined sales of Lipitor (atorvastatin), Zocor (simvastatin), Pravachol (pravastatin), Crestor (rosuvastatin) and Lescol/Lochol (fluvastatin) amounted to US$21.7 billion in 2005, around 2.6% more than in 2004.

Generic competition grows ever stronger in this sector and developers are extending their brands commercial life with the introduction of added benefit combination products.

New fixed-dose combinations aimed at improved cholesterol management or more than one heart disease risk factor are also likely to gain in popularity over the next few years with a number of companies exploiting combination products such as Merck & Co/Schering-Plough's Vytorin (ezetimibe+simvastatin). Additionally Pfizer is researching single therapy combination products such as atorvastatin and torcetrapib for cholesterol control.

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HYPERTENSION, CORONARY HEART DISEASE & HEART FAILURE
Hypertension is a leading risk factor for coronary heart disease, heart failure, heart attack, stroke and renal insufficiency. Hypertension is generally defined as blood pressure greater than 140/90mm Hg. Risk levels are doubled in people with diabetes.
The leading treatment for hypertension and coronary artery disease by sales value in 2005 was Pfizer's Norvasc (amlodipine) with sales of US$4.7 billion. The leading ARB is Novartis' Diovan/Co-Diovan (valsartan) with sales of US$3.7 billion in 2005, followed by Merck & Co.'s Cozaar/Hyzaar (losartan) with sales of US$3.2 billion in 2005, and Atacand/Blopress (candesartan cilexetil), which is marketed by sanofi-aventis and Takeda and achieved global sales for these two companies of US$2.4 billion in 2005. In total, sales of branded products for hypertension, coronary artery disease and heart failure by major pharmaceutical companies were in the region of US$29.5 billion in 2005.

New fixed-dose combinations aimed at more than one heart disease risk factor are also likely to gain in popularity over the next few years. Patients who suffer from both hypertension and high cholesterol levels have a much greater risk of suffering myocardial infarction or stroke than people who only have one of the conditions. Additionally, 60% of all cardiovascular events are experienced by patients who have both conditions.

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PULMONARY ARTERIAL HYPERTENSION
Pulmonary hypertension (PH) is defined by the WHO as a mean pulmonary artery pressure above 25 mmHg. Pulmonary arterial hypertension (PAH) is a rare form of PH. The ability of the blood vessels to function normally as blood flows to the lungs is adversely affected by the degradation of the blood vessel wall lining, the disruption of smooth muscle cell function and the aggregation of platelets, which combine to cause blockages.

The patient population for PAH is relatively small; an estimated 160,000 globally. The condition is often not diagnosed until it is quite advanced as early symptoms are often similar to other conditions, such as asthma. Early symptoms include dyspnoea (shortness of breath), chronic fatigue, dizziness, fainting, oedema and chest pain, especially during physical activity.

Mild to moderate PAH is currently treated with a variety of drugs including calcium channel blockers, diuretics and anticoagulants. While not specifically approved for PAH, these drugs can alleviate some of the symptoms.
Until recently, treatment options were limited, particularly for patients with more severe PAH. There are, however, a number of new and potential entrants into this market.

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ATRIAL FIBRILLATION
Atrial fibrillation (AF) is a disorder in the rhythm of the atria which reduces the heart's ability to effectively pump blood. AF can result in a rapid, irregular heart beat and pulse. In addition, blood which is not completely pumped out of the atria may pool and clot, increasing the risk of stroke. Around 15% of strokes occur in people with AF. According to the American Heart Association, around 2.2 million Americans have AF. The risk of developing AF increases with age; as the population ages, the number of people with this condition is likely to increase. By 2025, the number of people in the US with AF is projected to increase to around 3.8 million and by 2050 it could be as high as 5.6 million.

Current treatments for AF include drugs, electrical cardioversion to restore sinus rhythm with an electric shock, radio frequency ablation to destroy tissue that triggers abnormal electrical signals or to block abnormal electrical pathways, surgery or pacemakers to regulate the rhythm.

Current drug treatments include Cordarone (amiodarone), Corvert (ibutilide), Tambocor (flecainide), Rythmol (propafenone), Cardioquine (quinidine), Betapace (sotalol) and Tikosyn (dofetilide). These are limited by modest efficacy or potentially serious side effects.

The market for AF is relatively untapped, although there are numerous drugs in the pipeline. The most advanced is dronedarone, a novel multi-channel blocker developed by sanofi-aventis. Dronedarone is currently under regulatory review and, if approved, could replace Cordarone (amiodarone) as market leader.

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THROMBOSIS
Including atherothrombosis and venous thrombosis treatments

Thrombosis is the general term for the formation of a blood clot in the arteries or the veins that obstructs blood flow. The combined sales of leading anti-coagulant and anti-platelet drugs to treat atherothrombosis and venous thrombosis was in excess of US$11 billion in 2005, making this the third largest cardiovascular category in terms of sales.

The leading treatment for atherothrombosis is Plavix/Iscover (clopidogrel), which is jointly marketed by sanofi-aventis and Bristol-Myers Squibb. In 2005, sales of Plavix/Iscover (clopidogrel) for both companies amounted to around US$6.4 billion. sanofi-aventis also markets the leading treatment for venous thrombosis, Lovenox (enoxaparin), which had sales approaching US$2.8 billion in 2005.