“Statins, especially in combination with a good diet and regular exercise, have been proven to decrease the risk of heart attack and stroke, lessen the need for heart surgery and angioplasty, and reduce the risk of death significantly. An overview of prevention trials using both drugs and diet to lower cholesterol demonstrated an approximate 25% reduction in nonfatal and 14% in fatal (deadly) heart attacks,” explained my cardiologist after diagnosing my illness and reviewing the investigations. This stimulated me to learn more about the subject of high cholesterol and specially about this new class of drugs. The conclusion of my ‘google search’ was, “Statins are the new class of drugs, introduced in the current decade. These have been shown to have a major impact on heart disease progress. They have been studied extensively and have proven to be a safe and effective way to help patients lower their cholesterol levels,”
As a literate patient I wanted to update my self on current information and intend to share it with you. My first priority was to understand, what is primary and secondary prevention? Primary prevention is for people without any evidence of heart problem and secondary prevention is for patients who already have evidence of cardiac problems. My second aim was to look at the basic data and try to learn about the landmark studies which revolutionized the way the patients of coronary artery disease are treated. My aim was to learn the actual figures beyond non specific terms like mild, moderate and severe. Many small and large studies have been conducted with statin in the scenario of primary and secondary prevention and it is not possible to go over all of them, therefore we will confine our discussion to some important trials. My third aim was to look at safety data for personal reassurance.
The importance of high cholesterol as an important risk factors had always been appreciated by doctors and lay people. Many studies done in the past, employing large populations and different cholesterol lowering strategies failed to show any significant reduction in death rate. Statins used in this setting for the first time have shown very reliable data, that shows reduction of death rate in persons without any evidence of coronary artery disease. The data is not only convincing for people with high cholesterol but also very encouraging in patients with not so high cholesterol.
For the first time, the world of medicine received the news of statins’s efficacy in a population with no existing heart problem, by a study done in Scotland. This evaluated the role of statin in primary prevention in a relatively high risk population. After a 5-year period treatment a significant reduction of 31 percent was achieved in the defined primary endpoint. Total death rate was reduced with no increase in noncardiac death rates. When taking into account suspected coronary events, deaths from coronary artery disease decreased by 33 percent. It reported marked reduction in requirement of coronary angiography and revascularization procedures. The trial established the benefit of statin therapy in a high-risk group. The statin (Pravastatin) demonstrated a significant reduction in death and nonfatal heart attacks.
What does it mean to us as patients? Pravastatin therapy in male subjects with similar patient characteristics to the trial would prevent one event in 31 subjects who take statin therapy over a 5-year period. A conservative estimate of the feasibility of treating patients like those was determined to be well within the range of interventions that are considered to be cost effective approximately $ 13,000 US per year of life saved.
After evaluating the effects of lowering cholesterol in high risk patients, I searched for effects of cholesterol lowering in medium or low risk groups. I found a study that examined the potential impact of statin therapy in subjects including both middle-aged men and women whose total cholesterol approximated the average cholesterol. Lovastatin therapy resulted in a statistically significant 37 percent reduction in the incidence of primary endpoint event. Lovastatin therapy resulted in consistent reductions in event rates in the secondary endpoints: a moderate riask reduction in evascularizations, unstable angina, and nonfatal or fatal heart attack. Among patient subgroups in the group (e.g., women, smokers, and hypertensives), the benefit of lovastatin treatment was comparable with the benefit in the overall cohort. This was the first major clinical trial of a statin to demonstrate reductions in first coronary events in a low-risk subgroup whose profile approximates the general population.
Secondary prevention studies are conducted in patients with established coronary artery disease, offering new insights and directions in the management of coronary artery disease. For the first time we have very convincing data that shows mortality benefit by altering cholesterol levels favourably in patients with high and not so high cholesterol and established coronary artery disease.
A new piece of information that set new trends in heart diseases management came from a study called 4S. This landmark trial demonstrated clearly that statin therapy could reduce total mortality in a secondary prevention situation. The most significant impact on mortality was due to the reduction in heart events. A number of substudies were also performed and demonstrated that Simvastatin therapy was effective in women and older patients - age more than 60 years. Cerebrovascular events (strokes) and new carotid bruits were also significantly reduced by the therapy. This was a large-scale trial that evaluated the effect of Simvastatin therapy in patients with high cholesterol who were either heart attack survivors, patients with angina, or both in a 5.4 year trial.
Very interesting and exciting data was provided by an extremely large secondary prevention trial that evaluated statin (Pravastatin) in patients over a period of 6.1 years. Overall death rate was 22 percent less in the group randomized to statin, which was highly statistically significant. The relative risk reduction by statin in deaths from heart diseases was reduced by 24 percent as compared to placebo. A number of secondary endpoints, including the incidence of heart attacks, revascularization procedures like angioplasty and bypass, hospitalization for unstable angina, stroke and hospital days, were significantly reduced by Statin therapy.
This trial provided extremely strong evidence because of its large and diverse population. It showed that treatment with statin (pravastatin) in secondary prevention is of clinical benefit across a broad range of baseline cholesterol values and is associated with a reduction in total and cardiac mortality without an increase in noncardiac deaths. It became easy, to understand the magnitude of benefit, when I learnt that for every 1000 patients assigned to treatment with statin (pravastatin) over a period of 6 years, a total of 30 deaths, 28 nonfatal heart attacks, and nine nonfatal strokes could be avoided.
New trends were set by a remarkable trial called Heart Protection Study (HPS) that involved 20,000 volunteers, who were at high risk of coronary heart disease. Cholesterol lowering with statin treatment, reduced the risk of heart attacks and strokes by at least one-third. It reduced the need for bypass surgery, angioplasty and amputations by one third. Reductions of at least one-third in these ‘major vascular’ events were found in a very wide range of high risk patients for whom, there had previously been uncertainty about using cholesterol lowering therapy: women as well as men, people aged over 70 as well as younger people, people with blood levels of total cholesterol below 200 mg/dl or of ‘bad’ LDL cholesterol below 120 mg/dl, as well as those considered to have ‘high’ levels.
It was easy for me to understand that about 5 years of statin treatment typically prevents heart attacks, strokes or other major vascular events in: 100 of every 1000 people who previously had a heart attack, 80 of every 1000 people with angina or some other evidence of heart disease, 70 of every 1000 patients who previously had a stroke, 70 of every 1000 people with occlusive disease in leg or other arteries, 70 of every 1000 people with diabetes. I appreciated that in addition, cholesterol lowering reduces the risk of being hospitalized because of worsening angina typically, about 30 fewer admissions per 1000 treated for 5 years. The interesting aspect was that the benefits increased throughout the study treatment period (so more prolonged therapy might be expected to produce even bigger benefits), and are additional to those of other treatments used to prevent heart attacks and strokes.
My third aim was to study the side effects profile. Main side effects pertaining to statins are the effects on muscles and liver. The muscles can be effected by statins ranging from asymptomatic rise in a blood test called creatine kinase and muscle pain to frank rhabdomylosis-destruction of muscles. The evidence that statin drugs may also be associated with development of rhabdomyolysis (destruction of muscles) and kidney failure is understandably of concern. But we have to be careful to understand the extent of problem and not to throw the baby out with the bath water. Whether different statin-fibrate combinations have different risks for rhabdomyolysis (destruction of muscles) is not yet known. In fact, several recent studies have shown other statins and combinations to be effective without evidence of abnormal biochemical test. Results confirm that in large patient data base employing different statins, rhabdomyolysis (destructions of muscles) was extremely rare. Rise in CPK, indicating muscle involvement is comparable with placebo. However this side effect should be kept in mind and drugs which increase the likehood of muscle disese – myopathy should be avoided. Patients on statins presenting with muscle pain and aches should have their CPK checked. The drug should be discontinued if myopathy is suspected, if CPK levels rise markedly, or if the patient has risk factors for rhabdomyolysis (destruction of muscles).
Liver can be effected by statins. Effects can be asymptomatic mild to marked rise of blood test of liver called serum transaminase or frank jaundice. In majority of cases the rise of enzyme is transitory and almost always reversible on discontinuation of therapy. Mild increase in transaminsase (2-4 upper limit of normal), does not warrant cessation of therapy. Close monitoring and reduction of dose is usually sufficient. If the rise is more than 4 times then the drugs should be stopped. A different statin at a lower dose may be initiated and the dose built up slowly. Liver function should be monitored, before treatment is started and periodically checked thereafter like twice a year, for the first year of treatment or until 1 year after the last elevation in dose. Patients titrated to high dosage should receive an additional liver function test at 3 months.
To conclude, it has been proven that an average reduction of cholesterol by 40 mg/dl for about 5 years will result in reduction in non fatal and fatal heart attack by about one fourth. Similar effects are seen in people with no evidence of coronary artery disease and having high or not so high cholesterol. The data is quite encouraging for patients with evidence of coronary artery disease and having high or normal levels of cholesterol. Similar benefits await persons with average or high cholesterol with no heart problem.
The side effects may sound alarming but are very rare and do not require very close monitoring in majority of patients: these side effects should not prevent the more wide spread application of this “new aspirin”.
American College of Cardiology and Amerian Heart Association reassured patients about statin effectiveness and safety and the President of ACC Douglas P Zipes declared.
“While statins like all other drugs have side effects the benefits of using statins to manage patients cholesterol far outweighs the risk of serious side effects from their use. We want to reassure patients that statins have proven to be safe and very effective drugs and we urge patients who are taking statins and have no side effects to continue taking the drug.”
___________________________________________________
Ref: Heal Thy Heart written by Prof: Dr. Muhammad Hafizullah
As a literate patient I wanted to update my self on current information and intend to share it with you. My first priority was to understand, what is primary and secondary prevention? Primary prevention is for people without any evidence of heart problem and secondary prevention is for patients who already have evidence of cardiac problems. My second aim was to look at the basic data and try to learn about the landmark studies which revolutionized the way the patients of coronary artery disease are treated. My aim was to learn the actual figures beyond non specific terms like mild, moderate and severe. Many small and large studies have been conducted with statin in the scenario of primary and secondary prevention and it is not possible to go over all of them, therefore we will confine our discussion to some important trials. My third aim was to look at safety data for personal reassurance.
The importance of high cholesterol as an important risk factors had always been appreciated by doctors and lay people. Many studies done in the past, employing large populations and different cholesterol lowering strategies failed to show any significant reduction in death rate. Statins used in this setting for the first time have shown very reliable data, that shows reduction of death rate in persons without any evidence of coronary artery disease. The data is not only convincing for people with high cholesterol but also very encouraging in patients with not so high cholesterol.
For the first time, the world of medicine received the news of statins’s efficacy in a population with no existing heart problem, by a study done in Scotland. This evaluated the role of statin in primary prevention in a relatively high risk population. After a 5-year period treatment a significant reduction of 31 percent was achieved in the defined primary endpoint. Total death rate was reduced with no increase in noncardiac death rates. When taking into account suspected coronary events, deaths from coronary artery disease decreased by 33 percent. It reported marked reduction in requirement of coronary angiography and revascularization procedures. The trial established the benefit of statin therapy in a high-risk group. The statin (Pravastatin) demonstrated a significant reduction in death and nonfatal heart attacks.
What does it mean to us as patients? Pravastatin therapy in male subjects with similar patient characteristics to the trial would prevent one event in 31 subjects who take statin therapy over a 5-year period. A conservative estimate of the feasibility of treating patients like those was determined to be well within the range of interventions that are considered to be cost effective approximately $ 13,000 US per year of life saved.
After evaluating the effects of lowering cholesterol in high risk patients, I searched for effects of cholesterol lowering in medium or low risk groups. I found a study that examined the potential impact of statin therapy in subjects including both middle-aged men and women whose total cholesterol approximated the average cholesterol. Lovastatin therapy resulted in a statistically significant 37 percent reduction in the incidence of primary endpoint event. Lovastatin therapy resulted in consistent reductions in event rates in the secondary endpoints: a moderate riask reduction in evascularizations, unstable angina, and nonfatal or fatal heart attack. Among patient subgroups in the group (e.g., women, smokers, and hypertensives), the benefit of lovastatin treatment was comparable with the benefit in the overall cohort. This was the first major clinical trial of a statin to demonstrate reductions in first coronary events in a low-risk subgroup whose profile approximates the general population.
Secondary prevention studies are conducted in patients with established coronary artery disease, offering new insights and directions in the management of coronary artery disease. For the first time we have very convincing data that shows mortality benefit by altering cholesterol levels favourably in patients with high and not so high cholesterol and established coronary artery disease.
A new piece of information that set new trends in heart diseases management came from a study called 4S. This landmark trial demonstrated clearly that statin therapy could reduce total mortality in a secondary prevention situation. The most significant impact on mortality was due to the reduction in heart events. A number of substudies were also performed and demonstrated that Simvastatin therapy was effective in women and older patients - age more than 60 years. Cerebrovascular events (strokes) and new carotid bruits were also significantly reduced by the therapy. This was a large-scale trial that evaluated the effect of Simvastatin therapy in patients with high cholesterol who were either heart attack survivors, patients with angina, or both in a 5.4 year trial.
Very interesting and exciting data was provided by an extremely large secondary prevention trial that evaluated statin (Pravastatin) in patients over a period of 6.1 years. Overall death rate was 22 percent less in the group randomized to statin, which was highly statistically significant. The relative risk reduction by statin in deaths from heart diseases was reduced by 24 percent as compared to placebo. A number of secondary endpoints, including the incidence of heart attacks, revascularization procedures like angioplasty and bypass, hospitalization for unstable angina, stroke and hospital days, were significantly reduced by Statin therapy.
This trial provided extremely strong evidence because of its large and diverse population. It showed that treatment with statin (pravastatin) in secondary prevention is of clinical benefit across a broad range of baseline cholesterol values and is associated with a reduction in total and cardiac mortality without an increase in noncardiac deaths. It became easy, to understand the magnitude of benefit, when I learnt that for every 1000 patients assigned to treatment with statin (pravastatin) over a period of 6 years, a total of 30 deaths, 28 nonfatal heart attacks, and nine nonfatal strokes could be avoided.
New trends were set by a remarkable trial called Heart Protection Study (HPS) that involved 20,000 volunteers, who were at high risk of coronary heart disease. Cholesterol lowering with statin treatment, reduced the risk of heart attacks and strokes by at least one-third. It reduced the need for bypass surgery, angioplasty and amputations by one third. Reductions of at least one-third in these ‘major vascular’ events were found in a very wide range of high risk patients for whom, there had previously been uncertainty about using cholesterol lowering therapy: women as well as men, people aged over 70 as well as younger people, people with blood levels of total cholesterol below 200 mg/dl or of ‘bad’ LDL cholesterol below 120 mg/dl, as well as those considered to have ‘high’ levels.
It was easy for me to understand that about 5 years of statin treatment typically prevents heart attacks, strokes or other major vascular events in: 100 of every 1000 people who previously had a heart attack, 80 of every 1000 people with angina or some other evidence of heart disease, 70 of every 1000 patients who previously had a stroke, 70 of every 1000 people with occlusive disease in leg or other arteries, 70 of every 1000 people with diabetes. I appreciated that in addition, cholesterol lowering reduces the risk of being hospitalized because of worsening angina typically, about 30 fewer admissions per 1000 treated for 5 years. The interesting aspect was that the benefits increased throughout the study treatment period (so more prolonged therapy might be expected to produce even bigger benefits), and are additional to those of other treatments used to prevent heart attacks and strokes.
My third aim was to study the side effects profile. Main side effects pertaining to statins are the effects on muscles and liver. The muscles can be effected by statins ranging from asymptomatic rise in a blood test called creatine kinase and muscle pain to frank rhabdomylosis-destruction of muscles. The evidence that statin drugs may also be associated with development of rhabdomyolysis (destruction of muscles) and kidney failure is understandably of concern. But we have to be careful to understand the extent of problem and not to throw the baby out with the bath water. Whether different statin-fibrate combinations have different risks for rhabdomyolysis (destruction of muscles) is not yet known. In fact, several recent studies have shown other statins and combinations to be effective without evidence of abnormal biochemical test. Results confirm that in large patient data base employing different statins, rhabdomyolysis (destructions of muscles) was extremely rare. Rise in CPK, indicating muscle involvement is comparable with placebo. However this side effect should be kept in mind and drugs which increase the likehood of muscle disese – myopathy should be avoided. Patients on statins presenting with muscle pain and aches should have their CPK checked. The drug should be discontinued if myopathy is suspected, if CPK levels rise markedly, or if the patient has risk factors for rhabdomyolysis (destruction of muscles).
Liver can be effected by statins. Effects can be asymptomatic mild to marked rise of blood test of liver called serum transaminase or frank jaundice. In majority of cases the rise of enzyme is transitory and almost always reversible on discontinuation of therapy. Mild increase in transaminsase (2-4 upper limit of normal), does not warrant cessation of therapy. Close monitoring and reduction of dose is usually sufficient. If the rise is more than 4 times then the drugs should be stopped. A different statin at a lower dose may be initiated and the dose built up slowly. Liver function should be monitored, before treatment is started and periodically checked thereafter like twice a year, for the first year of treatment or until 1 year after the last elevation in dose. Patients titrated to high dosage should receive an additional liver function test at 3 months.
To conclude, it has been proven that an average reduction of cholesterol by 40 mg/dl for about 5 years will result in reduction in non fatal and fatal heart attack by about one fourth. Similar effects are seen in people with no evidence of coronary artery disease and having high or not so high cholesterol. The data is quite encouraging for patients with evidence of coronary artery disease and having high or normal levels of cholesterol. Similar benefits await persons with average or high cholesterol with no heart problem.
The side effects may sound alarming but are very rare and do not require very close monitoring in majority of patients: these side effects should not prevent the more wide spread application of this “new aspirin”.
American College of Cardiology and Amerian Heart Association reassured patients about statin effectiveness and safety and the President of ACC Douglas P Zipes declared.
“While statins like all other drugs have side effects the benefits of using statins to manage patients cholesterol far outweighs the risk of serious side effects from their use. We want to reassure patients that statins have proven to be safe and very effective drugs and we urge patients who are taking statins and have no side effects to continue taking the drug.”
___________________________________________________
Ref: Heal Thy Heart written by Prof: Dr. Muhammad Hafizullah
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