“We know what we are but we know not what we may be.” Shakespeare (Ophelia, in Hamlet).
Angiotensin converting enzyme inhibitors are a group of drugs for which many more indications were ‘invented’ as the experience accumulated in clinical practice for some time. Initially introduced in early eighties, as a treatment for difficult to control high blood pressure, it has now been used in most heart related diseases. There are very few patients with a significant heart ailment, who leave a cardiology unit without an ACE inhibitor on their discharge slips.
Angiotensin converting enzyme inhibitors are the most widely prescribed drugs in patients with heart problems due to high blood pressure and heart failure. They have an extremely successful track record for lowering systolic and diastolic blood pressure and have been employed usefully in the setting of symptomatic and asymptomatic heart failure and after a heart attack. There are many agents with distinct chemical characteristics and metabolism. Some are given thrice a day and others with long half life are used once a day. They are available in many preparations like Captopril, Enalapril, Lisinopril, Ramipril, Fosinopril etc.
How do they work? They work by inhibiting the formation of a very potent chemical called Angiotensin II, which causes most intense contriction/narrowing of vessels. Due to reduced formation of this agent, vessels are prevented from constricting or conversely allowed to dilate. Besides direct physical effects, it also exerts many other potentially beneficial effects by influencing the hormone release from brain like RAA and sympathetic system.
1. High blood pressure:
They were introduced in the market as potent drugs to reduce both systolic and diastolic blood pressure. They are very effective in bringing blood pressure down in both genders and all age groups. It works quickly and has a sustained effect. Left ventricle – the main pumping chamber develops thickness of walls as a response to pumping blood against high blood pressure. It has been shown to be most effective in reducing this thickness and reversal to normal. It has a benign profile and is well tolerated by majority of patients. As against other classes of anti hypertensive agents, it has no major contraindication so it is a drug of choice in most patients. It is used in preference to others in patients with thickened heartwalls, those in heart failure, poor heart function and after a heart attack. It should not be used in pregnant patients.
2. Heart failure:
Heart failure is the end result of all disease processes effecting the heart. Heart failure implies a condition where heart cannot meet the demands of body. Previously doctors had to solely rely on water tablets to reduce water in body and decrease load on heart. In many short term and long term trials the benefit of ACE inhibitors have been proven to reduce the load on heart – both pre load and after load. In our practice, we ensure that all patients of heart failure receive adequate doses of ACE inhibitors and continue to use them for all times to come. Under the umbrella of ACE inhibitors, the dosage of water tablets called diuretics can be reduced and sometimes totally stopped. Patients feel a lot better with improvement in their symptoms and exercise capacity. The drug can be used for patients in severe, moderate or mild failure. The benefits are equally impressive in all three groups of patients. These effects are independent of blood pressure reduction. Moreover, even patients with low blood pressure, can tolerate adequate doses of ACE inhibitors.
3. Poor heart (LV) function:
Having proven its benefit in patients with obvious heart failure, ACE inhibitors were then tried in patients with no signs of heart failure but having evidence of poor heart function documented on echocardiography or nuclear studies. By using ACE inhibitors in this specific group, patients’ progress to development of symptomatic heart failure can be decreased in a majority of patients or totally avoided in a minority of subjects. This has significant bearing on their eventual outcome in terms of frequency of hospitalizations and death.
4. Heart attack:
In a heart attack a portion of heart is rendered dead/necrotic due to cessation of blood supply. This area stops moving hence makes no contribution towards contraction and pumping of blood. Depending on the site and the vessel involved this may be a small or a large area. Heart tries to compensate for this loss and tries to preserve the output. This puts extra load on adjoining segments. Heart size might increase as the dead tissue is stretched by over zealous contraction of normal segments. This is called remodeling on heart. ACE inhibitors have been used to reverse this process. They have been shown to reverse the remodeling and prevent enlargement of heart size. This would naturally mean lesser number of patients developing heart failure with fewer deaths. ACE inhibitors have become an integral part of treatment for patients sustaining a heart attack.
5. Stroke:
High blood pressure remains the most important contributing factor towards stroke. The reduction of blood pressure is associated with most significant effects on reduction of stroke. Patients with stroke have a high propensity to develop another stroke especially if risk factors are not addressed and corrected. Beyond the reduction of blood pressure, ACE inhibitors have been shown to have a beneficial effect on prevention of stroke and reduction of associated mortality and morbidity. The theory has been postulated that certain ACE inhibitor may have a specific role to play which cannot be explained merely on reduction of blood pressure. Many neurologists, now, routinely use ACE inhibitors in patients after stroke even if the blood pressure is not very high.
6. Stable angina:
Patients with stable angina are normally treated with drugs for symptomatic relief and disease modifying drugs. Whereas Nitrates, Beta blockers and Calcium channel blockers may be employed for symptomatic relief, drugs like Aspirin and Statin have effects on modifying the course of disease. Similarly, ACE inhibitors have now been shown to have disease modifying effects, with significant effects on eventual events like episodes of angina, hospitalization, requirement of procedures like angiography and angioplasty and reduced frequency of death. It has been recommended as a drug to be used in patients with angina with normal or raised blood pressure.
7. High risk patients:
Considering multitude effects of ACE inhibitors, a new challenging role was investigated in a large well conducted trial. Patients with multiple risk factors and higher risk of developing coronary artery disease were studied in a large trial by administering ACE inhibitors and compared with placebo. The results were very encouraging with significant reduction in development of heart attacks and episodes of unstable angina. There was a dramatic decrease in requirement of angiography, angioplasty and bypass surgery. The effects of ACE inhibitors were independent of blood pressure. Here ACE inhibitors are claiming a new role, independent of their ‘traditionally recognised’ effect on blood pressure. Many cardiologists believe that every one with multiple risk factors and high risk of developing heart problems should be prescribed ACE inhibitors for an indefinite time.
8. Renal Protienuria:
At one time patients used to be given Albustix with administration of Captopril – the first ACE inhibitor to monitor any release of protein in urine. The pendulum has swung in opposite direction and beneficial role of ACE inhibitors has been proven in patients with leakage of protein in urine. It has been established in various studies that ACE inhibitors reduce the total amount of protein leaked in twenty four hours with or without its effect on blood pressure.
9. Anti Ischaemia:
Newer ailments are being added to the conditions benefiting from Angiotensin converting enzyme inhibitors. Their new role of possessing anti ischaemic properties has come to limelight only recently. Do angiotensin converting enzyme inhibitors have anti ischaemic properties? ACE inhibitors do not have any consistent short term anti anginal effects. Attention has been focused on the potential long term benefits of ACE inhibitors in preventing ischemic events in patients with stable heart disease. This came as an unexpected finding from large clinical trials conducted in patients with severe, moderate and mild heart failure. A large trial called SOLVD study, for example, demonstrated a reduction in the risk of heart attacks (either first or recurrent) by 23% and the risk of unstable angina by 20% in the treated group. In another study, there was 25% reduction in recurrent heart attack as well as a significant reduction in the rate of revascularization including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) in the treated group.
It is unlikely that the observed reduction in ischaemic events can be explained by the blood pressure lowering action of ACE inhibitors alone, since the magnitude of risk reduction was substantially larger than that expected from short term modest reductions in blood pressure. In a recent analysis of 14 trials of blood pressure treatment, diastolic blood pressure reduction of 5 mmHg for about 5 years showed a 14% reduction in fatal and nonfatal heart related events. In a large trial, diastolic blood pressure was reduced by an average of 4 mmHg; this was associated with a 23% reduction in fatal or nonfatal heart attacks and a marked reduction in cardiac deaths. Moreover, the risk reduction in ischemic events were similar in patients with different levels of blood pressure at baseline. In another study, the effects of ACEI were studied on stable patients with heart disease, and the results were impressive reduction in adverse heart related events. Similar results were obtained in high risk population with and without heart diseases. ACE inhibitors exert an indirect anti atherogenic action by reducing vascular smooth muscle growth and proliferation, restoring endothelial function and by reducing the propensity for a plaque to rupture.
Side effects:
By and large ACE inhibitors are very well tolerated. The side effects profile is benign except that it produces persistent hacking cough, which does not respond to cough suppressants. This has been reported differently in different trials but can be observed in up to 10-15% of patients. The cough responds only to stopping of the drug. In patients presenting with persistent cough, sister products of ACE inhibitors called Angiotensin receptor blockers have been used with almost similar efficacy but without cough. Many trials have documented the efficacy and safety of this relatively new group of drugs.
To conclude, ACE inhibitors, initially introduced as anti hypertensive agent, in difficult to control patients at high dosage, newer roles have been discovered and the drug is being used in almost all types of heart problems. ACE inhibitors seem to possess some anti ischemic properties and confer the beneficial effects through various mechanisms but more direct evidence should be sought from large clinical trials to further clear the picture. The question that should all patients with heart disease be receiving ACE inhibitors has now entered into a practical phase and needs serious consideration.
___________________________________________________
Ref: Heal Thy Heart written by Prof: Dr. Muhammad Hafizullah
Angiotensin converting enzyme inhibitors are a group of drugs for which many more indications were ‘invented’ as the experience accumulated in clinical practice for some time. Initially introduced in early eighties, as a treatment for difficult to control high blood pressure, it has now been used in most heart related diseases. There are very few patients with a significant heart ailment, who leave a cardiology unit without an ACE inhibitor on their discharge slips.
Angiotensin converting enzyme inhibitors are the most widely prescribed drugs in patients with heart problems due to high blood pressure and heart failure. They have an extremely successful track record for lowering systolic and diastolic blood pressure and have been employed usefully in the setting of symptomatic and asymptomatic heart failure and after a heart attack. There are many agents with distinct chemical characteristics and metabolism. Some are given thrice a day and others with long half life are used once a day. They are available in many preparations like Captopril, Enalapril, Lisinopril, Ramipril, Fosinopril etc.
How do they work? They work by inhibiting the formation of a very potent chemical called Angiotensin II, which causes most intense contriction/narrowing of vessels. Due to reduced formation of this agent, vessels are prevented from constricting or conversely allowed to dilate. Besides direct physical effects, it also exerts many other potentially beneficial effects by influencing the hormone release from brain like RAA and sympathetic system.
1. High blood pressure:
They were introduced in the market as potent drugs to reduce both systolic and diastolic blood pressure. They are very effective in bringing blood pressure down in both genders and all age groups. It works quickly and has a sustained effect. Left ventricle – the main pumping chamber develops thickness of walls as a response to pumping blood against high blood pressure. It has been shown to be most effective in reducing this thickness and reversal to normal. It has a benign profile and is well tolerated by majority of patients. As against other classes of anti hypertensive agents, it has no major contraindication so it is a drug of choice in most patients. It is used in preference to others in patients with thickened heartwalls, those in heart failure, poor heart function and after a heart attack. It should not be used in pregnant patients.
2. Heart failure:
Heart failure is the end result of all disease processes effecting the heart. Heart failure implies a condition where heart cannot meet the demands of body. Previously doctors had to solely rely on water tablets to reduce water in body and decrease load on heart. In many short term and long term trials the benefit of ACE inhibitors have been proven to reduce the load on heart – both pre load and after load. In our practice, we ensure that all patients of heart failure receive adequate doses of ACE inhibitors and continue to use them for all times to come. Under the umbrella of ACE inhibitors, the dosage of water tablets called diuretics can be reduced and sometimes totally stopped. Patients feel a lot better with improvement in their symptoms and exercise capacity. The drug can be used for patients in severe, moderate or mild failure. The benefits are equally impressive in all three groups of patients. These effects are independent of blood pressure reduction. Moreover, even patients with low blood pressure, can tolerate adequate doses of ACE inhibitors.
3. Poor heart (LV) function:
Having proven its benefit in patients with obvious heart failure, ACE inhibitors were then tried in patients with no signs of heart failure but having evidence of poor heart function documented on echocardiography or nuclear studies. By using ACE inhibitors in this specific group, patients’ progress to development of symptomatic heart failure can be decreased in a majority of patients or totally avoided in a minority of subjects. This has significant bearing on their eventual outcome in terms of frequency of hospitalizations and death.
4. Heart attack:
In a heart attack a portion of heart is rendered dead/necrotic due to cessation of blood supply. This area stops moving hence makes no contribution towards contraction and pumping of blood. Depending on the site and the vessel involved this may be a small or a large area. Heart tries to compensate for this loss and tries to preserve the output. This puts extra load on adjoining segments. Heart size might increase as the dead tissue is stretched by over zealous contraction of normal segments. This is called remodeling on heart. ACE inhibitors have been used to reverse this process. They have been shown to reverse the remodeling and prevent enlargement of heart size. This would naturally mean lesser number of patients developing heart failure with fewer deaths. ACE inhibitors have become an integral part of treatment for patients sustaining a heart attack.
5. Stroke:
High blood pressure remains the most important contributing factor towards stroke. The reduction of blood pressure is associated with most significant effects on reduction of stroke. Patients with stroke have a high propensity to develop another stroke especially if risk factors are not addressed and corrected. Beyond the reduction of blood pressure, ACE inhibitors have been shown to have a beneficial effect on prevention of stroke and reduction of associated mortality and morbidity. The theory has been postulated that certain ACE inhibitor may have a specific role to play which cannot be explained merely on reduction of blood pressure. Many neurologists, now, routinely use ACE inhibitors in patients after stroke even if the blood pressure is not very high.
6. Stable angina:
Patients with stable angina are normally treated with drugs for symptomatic relief and disease modifying drugs. Whereas Nitrates, Beta blockers and Calcium channel blockers may be employed for symptomatic relief, drugs like Aspirin and Statin have effects on modifying the course of disease. Similarly, ACE inhibitors have now been shown to have disease modifying effects, with significant effects on eventual events like episodes of angina, hospitalization, requirement of procedures like angiography and angioplasty and reduced frequency of death. It has been recommended as a drug to be used in patients with angina with normal or raised blood pressure.
7. High risk patients:
Considering multitude effects of ACE inhibitors, a new challenging role was investigated in a large well conducted trial. Patients with multiple risk factors and higher risk of developing coronary artery disease were studied in a large trial by administering ACE inhibitors and compared with placebo. The results were very encouraging with significant reduction in development of heart attacks and episodes of unstable angina. There was a dramatic decrease in requirement of angiography, angioplasty and bypass surgery. The effects of ACE inhibitors were independent of blood pressure. Here ACE inhibitors are claiming a new role, independent of their ‘traditionally recognised’ effect on blood pressure. Many cardiologists believe that every one with multiple risk factors and high risk of developing heart problems should be prescribed ACE inhibitors for an indefinite time.
8. Renal Protienuria:
At one time patients used to be given Albustix with administration of Captopril – the first ACE inhibitor to monitor any release of protein in urine. The pendulum has swung in opposite direction and beneficial role of ACE inhibitors has been proven in patients with leakage of protein in urine. It has been established in various studies that ACE inhibitors reduce the total amount of protein leaked in twenty four hours with or without its effect on blood pressure.
9. Anti Ischaemia:
Newer ailments are being added to the conditions benefiting from Angiotensin converting enzyme inhibitors. Their new role of possessing anti ischaemic properties has come to limelight only recently. Do angiotensin converting enzyme inhibitors have anti ischaemic properties? ACE inhibitors do not have any consistent short term anti anginal effects. Attention has been focused on the potential long term benefits of ACE inhibitors in preventing ischemic events in patients with stable heart disease. This came as an unexpected finding from large clinical trials conducted in patients with severe, moderate and mild heart failure. A large trial called SOLVD study, for example, demonstrated a reduction in the risk of heart attacks (either first or recurrent) by 23% and the risk of unstable angina by 20% in the treated group. In another study, there was 25% reduction in recurrent heart attack as well as a significant reduction in the rate of revascularization including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) in the treated group.
It is unlikely that the observed reduction in ischaemic events can be explained by the blood pressure lowering action of ACE inhibitors alone, since the magnitude of risk reduction was substantially larger than that expected from short term modest reductions in blood pressure. In a recent analysis of 14 trials of blood pressure treatment, diastolic blood pressure reduction of 5 mmHg for about 5 years showed a 14% reduction in fatal and nonfatal heart related events. In a large trial, diastolic blood pressure was reduced by an average of 4 mmHg; this was associated with a 23% reduction in fatal or nonfatal heart attacks and a marked reduction in cardiac deaths. Moreover, the risk reduction in ischemic events were similar in patients with different levels of blood pressure at baseline. In another study, the effects of ACEI were studied on stable patients with heart disease, and the results were impressive reduction in adverse heart related events. Similar results were obtained in high risk population with and without heart diseases. ACE inhibitors exert an indirect anti atherogenic action by reducing vascular smooth muscle growth and proliferation, restoring endothelial function and by reducing the propensity for a plaque to rupture.
Side effects:
By and large ACE inhibitors are very well tolerated. The side effects profile is benign except that it produces persistent hacking cough, which does not respond to cough suppressants. This has been reported differently in different trials but can be observed in up to 10-15% of patients. The cough responds only to stopping of the drug. In patients presenting with persistent cough, sister products of ACE inhibitors called Angiotensin receptor blockers have been used with almost similar efficacy but without cough. Many trials have documented the efficacy and safety of this relatively new group of drugs.
To conclude, ACE inhibitors, initially introduced as anti hypertensive agent, in difficult to control patients at high dosage, newer roles have been discovered and the drug is being used in almost all types of heart problems. ACE inhibitors seem to possess some anti ischemic properties and confer the beneficial effects through various mechanisms but more direct evidence should be sought from large clinical trials to further clear the picture. The question that should all patients with heart disease be receiving ACE inhibitors has now entered into a practical phase and needs serious consideration.
___________________________________________________
Ref: Heal Thy Heart written by Prof: Dr. Muhammad Hafizullah
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