Staggering Costs of Strokes & Heart Attacks

Acquired Brain Injury – Cerebrovascular Accident (‘Stroke’)

‘Stroke’ refers to a group of conditions caused by the occlusion (blockage) or haemorrhage from blood vessels that supply the brain. Occlusion of the artery produces cerebral ischemia or brain cell death. Many stroke patients can either be left permanently disabled or instead die as a result of their stroke.

A majority of strokes involve the occlusion of an artery (conservatively assessed at 70% of all strokes) and the treatment-of-choice targets the reopening of an occluded artery using thrombolytics agents. Simply considering heart attacks, heart failure and stroke, this would result in a larger market that is estimated at 35.7 million people and approximately $8.2 billion in revenues.

The primary goal of current stroke management strategies is to improve the outcome in stroke survivors including general stroke therapies (recanalization of occluded vessel), as well as to effectively treat secondary complications (e.g. increased pressure in the brain).

Thrombolytic therapy is the current standard for treatment of stroke as it eliminates clots in the blocked blood vessels and restores blood flow to the affected brain regions. However, injury and cell death can occur as a result of the restoration of blood flow in the brain similar to the heart. Co-administration of drugs along with thrombolytics should help to minimize brain cell death from ischemia and a reperfusion injury.

Current treatment of acquired brain injury does not include the use of neuroprotectants to prevent neuronal cell death. Therefore, future classes of apoptotic inhibitors may prove both life-saving and critical to the effective reduction of any acute secondary complications associated with stroke.

Acute myocardial infarction (AMI) refers to the death of heart muscle usually as a consequence of acute interruption of blood flow to the heart. The amount of heart muscle lost during a heart attack is a critical determinant of the future pumping or contractile performance of the heart. Thus the greater the amount of muscle lost during an acute myocardial infarction, the greater the loss of cardiac function. Very large loss of cardiac muscle produces shock or death while large amounts leave the survivor of the heart attack in heart failure with limited functional capacity.

The treatment of patients in the acute stages of a heart attack is a multi-billion dollar market. Current disease management strategies are directed at dissolving the blood clot, blocking platelets clumping, preventing the effects of excessive catecholamines, preventing cholesterol build-up in the artery and allowing the heart to remodel.

There are a number of current strategies that are used for management of AMI. These include:

• General therapies e.g. supplemented oxygen and morphine
• Reopening the occluded coronary artery using fibrinolytic agents to dissolve the blood clot; angioplasty (a balloon catheter that is expanded in the blocked coronary vessel) and/or coronary artery stent to ensure that the artery remains open
• Increasing coronary blood flow and/or reducing the workload of the heart using beta-blockers (e.g. metoprolol), short and/or long-acting nitrate medications.
• Prevention of ongoing clot formation using anti-coagulants or anti-platelet medications
• Reduce plaque and artery inflammation using statins.
• Improvement of cardiac remodelling and compromised cardiac function to slow further deterioration in heart pumping action using ACE inhibitors or angiotensin receptor blockers

A recent paper by S. Rabkin (2009) reviews the evidence from 20 publications implicating apoptosis in 400 AMI patients. The major conclusions found in these studies are:

a)    during the early stages (initial 24 hours) of an AMI, apoptosis is the predominant form of cell death; apoptosis occurs in 60% of the heart cells found in the infarcted area.

b)    the greatest amount of apoptosis occurs in the early stages of AMI when patients present
to the hospital with acute pain that requires treatment..

c)    apoptosis continues to be evident long after the acute event and accelerated apoptosis occurs predominantly in that area of the heart that has suffered the greatest amount of cardiac damage.

The market for the treatment of myocardial infarction has unmet potential and unmet needs. There are currently no treatments in clinical use to directly prevent the death of cardiac muscle cells. There will be an increase in the overall number of fatalities occurring worldwide from ischemic and cerebrovascular disease by the year 2020. Heart attacks and strokes make up a major portion of these diseases therefore these overall numbers reflect what will occur in AMI and stroke patients. The combined annual mortality rate from ischemic heart and cerebrovascular disease in 1990 was estimated to be 4 million (38% of global incidence) in developed countries and 6.5 million (62%) in developing countries (Yusuf et al 2001) The overall mortality rate from ischemic heart and cerebrovascular disease will increase to 20.1 million, an increase greater than 90% in the number of worldwide fatalities during this 30 year period (Yusuf et al 2001).

Developing countries will be the primary drivers in the overall increase of fatalities due to these diseases. Aging of the global population will have a greater impact on developed countries. In developing countries, a growing middle class and increasing ‘Westernization’ of lifestyles in emerging markets will increase the incidence of these diseases.

If an approved anti-apoptotic agent were available today for AMI, it would be used as add-on (i.e. adjuvant) therapy and integrated into current treatment strategies as part of best practices. A physician would be expected to consider usage of the above to improve patient survival and help minimize future complication (e.g. heart failure, a second MI, etc.) and improve the chances of a rapid recovery.

Agents directed at breaking up the clot are a good marker for assessing the market size and potential of anti-apoptotic drugs in AMI. Thrombolytic agents are used as add-on therapy during an AMI and it is predicted that antiapoptotic agents would similarly be used as add-on therapy during the occurrence of an AMI. First-generation thrombolytics such as t-PA were estimated to generate revenues of US$ 400 million globally, with an estimated market size approaching US$1 billion (Bioportfolio 2002). One second-generation thrombolytics generated revenues of US $210 to 240 million. Thus the annual market for an anti-apoptotic agent for reduction of the severity of myocardial infarction is approximately US $600 million to US $1 billion.

In addition, as heart failure is the result of cardiac muscle cell death, the predicted heart failure reduction should be considered an essential  component of any health economic analysis of any potential products indicated for prevention of heart failure, aimed at the prevention of complications due to cell death in the respective cardiovascular and neurological therapeutic areas.

In summary, the extent of myocardial infarction is a direct determinant of long-term survival as well as any complications that may follow (e.g. heart failure); reducing the extent of myocardial infarction should always be a major goal in the treatment of myocardial infarction.