Abstract

The Physiology of treating heart failure has evolved over 10 years ago from symptom control to a strategy
of prevention and symptom-management. Pharmacological have shown early diagnosis can delay
progression. Treatment of left ventricular asymptomatic dysfunction is critical as treating symptomatic
disease. The aim of this review is to know the current guidelines for the primary care physician and the
specialist in heart failure for the pharmacological management of chronic systolic heart failure. In the
treatment of cardiac insufficiency, beginning prevention treatments together. Angiotensin-converting
enzyme inhibitors, beta-blockers, and diuretics are now standard therapies. Atenolol, Ramipril is added,
for patients, to improve the clinical symptoms. In select patients with stable heart failure class III or IV
of the New York Heart Association, antagonists of aldosterone may be recommended. If angiotensin-
converting enzyme inhibitors not accepted, blockers are recommended for angiotensin receptors,
hydralazine hydrochloride, and diuretics . For antiarrhythmic therapies and anticoagulation inconclusive.

Key words
Pathophysiology of heart failure, beta-blockers(Atenolol), Diuretics (Furosemide), ACE inhibitor
(Ramipril)
1_Introduction
Heart failure HF is a complex and serious clinical syndrome, which the heart not able to reach the metabolic of
the body. either resulting Poor Myocardial relaxation, impaired ejection or a mixture of both and different
pathological conditions would then make treatment and management complex. At first, patients could tolerate
small output declines as different compensatory measures are activated to rectify the balance. However, over
time these compensatory measures become deleterious to heart function and make the heart output worsening,
resulting in even more activation and extra output of blood on a failing heart. , ischaemic heart disease ( IHD)
(hypertension)as atrial fibrillation ( AF) , where a diagnosis is related ,. The European Cardiology Society,
however, defines for HF such as a clinical syndrome marked by symptoms such as shortness of exhalation,
persistent coughing or wheezing, swelling of the ankles and fatigue that can accompanie by the following
signs: high venous jugular pressure; pulmonary crackles; increased heart rate; and peripheral oedema (1) and a
lot of factors can also be affecting in heart failure such as An Old Age Population with continued to improve
chronic management Diseases, improved acute coronary syndrome therapies, And better treatment of HF
patients leading to improvement The results are a few possibilities which lead to a rise Statistics, Incidence of
HF increases with Age from approximately 20 per 1000 ages 60-65 to over Of those are especially important
given the fact that African Americans are most at risk for HF And a higher mortality rate than the white
population for five years, Absolute mortality rates for HF during the last few decades Within five years, they
remained at 50 per cent Diagnose . HF can be used in a number of classification schemes. These can be focused
on anatomical research results, for example, chamber of the right or left of the Cardiac or functional, based on
patient symptoms. Presentation, treatment , and prognosis can vary considerably Concentrated on the above
schemes of classification, and important For all providers to have their patients clearly classified into one In
such types. The words “systolic” and “diastolic” HF Was historically used but now recommended
Nomenclature is HF with conserved or decreased ejection Division.(2_6)
 Figure 1: Representation of cardiac output in relation to ejection fraction

2- Pathophysiology of heart failure

several disorders have been causing heart failure, such as disease causing the pericardium, myocardium,
endocardium, cardiac valves, vasculature, or metabolism. Idiopathic dilated cardiomyopathy (DCM), heart
disease (ischemic), hypertension, and valvular disease are the most popular causes of systolic dysfunction
(HfrEF). ncluding hypertrophic obstructive cardiomyopathy, and restrictive cardiomyopathy The physiological
mechanisms that could be sufficient to be maintain the total contractile performance to the heart at reasonably
normal levels become ill-adapted when attempting to maintain adequate cardiac output Myocyte hypertrophy,
death from apoptosis, and regeneration are the primary myocardial response to chronically increased stress in
the wall. Ultimately, this process leads to remodeling, commonly the excentric type, and reduced heart output,
going to cause a cascade of neurohumoral and vascular mechanism.The reduced stimulation of carotid
baroreceptors and renal perfusion would also activate the sympathetic nervous system and the aldosterone-
renin-angiotensin-system. Activation of sympathetic nervous system can cause elevated heart rate and inotropy,
resulting in toxicity to the myocardial. Renin-Angiotensin- Aldosterone Activation of the system results in
vasoconstriction, increased afterload (angiotensin II), and hemodynamic changes, increased preload
(aldosterone). Both of these processes can induce detrimental remodeling and aggravate left ventricular activity,
causing heart failure symptoms. (7)
Fig. 2. Remodeling of heart failure. Gross pathology. Fig. 3. Cardiac magnetic resonance imaging (CMR) inHeart failure
.Shows marked biventricular dilation with normal
Thickness in a patient with chronic systolic heart failure.

.
3- heart failure treatment

Congestive Heart Failure (CHF) Malik A, Brito D, Chhabra L.Diuretics, beta-blockers, angiotensin receptor
blockers (ARB) , angiotensin converting enzyme inhibitors (ACE inhibitor) ,angiotensin receptor neprilysin
inhibitor( ARNI) hydralazine plus nitrate, digoxin, Could cause symptoms to improve Beta-blockers, ,
angiotensin-receptor neprilysin inhibitors, hydralazine plus nitrate, and aldosterone antagonists have reported to
improve patient survival. Diuretic treatment provides more limited proof of the survival value. Replace
angiotensin converting enzyme inhibitors or angiotensin receptor blockers with angiotensin neprilysin inhibitors
in chronic symptomatic patients with CHF NYHA class II-III with sufficient blood pressure who tolerate an
appropriate dose of these medicines. Neprilysine to the angiotensin receptor Inhibitors should not be
administered within 36 hours of enzyme-converting angiotensin In African-American patients with persistent
NYHA class III to IV HF and LVEF, hydralazine plus oral nitrate is less than 40 percent, despite optimal
medical therapy (beta-blocker, enzyme-converting angiotensin inhibitors, ARB, aldosterone antagonist and
diuretic .

1_Beta blockers (Atenolol)

 Fig. 4. Atenolol 100mg tablet

1.1.mechanism of Action

Atenolol beta-1-adrenergic antagonists(Cardioselective) work as selectively binding the beta-1 adrenergic

receptors attatched in the vascular smooth muscle in addition to heart, preventing the activity of the positive
inotropic and chronotropic of endogenous catecholamines like isoproterenol, norepinephrine and epinephrine,
thereby preventing sympathetic stimulationThis operation results in reduced heart rate , blood pressure and
reduced contractility to the myocardial. Even so, atenolol can increase end-diastolic pressure and left ventricular
fiber lengths in patients with heart failure-which in turn results in increased demand for It also exerts its effects
in higher doses by highly competitive blocking beta-2-adrenoreceptors located mainly in the bronchial and
vascular musculature. Atenolol has poor lipid solubility due to lack of membrane stabilization or intrinsic
sympathomimetic activity, and decreased brain penetration contributes to less adverse effects of the CCN. Beta-
adrenergic antagonists of the receptors also are known to increase the refractory period of the AV node. Hence
it could also be used off-licensing for the treatment of supraventricular tachycardia and the prevention of atrial
fibrillation paroxysmal attacks. .(8)The period of action being dose-related-the effects are noticeable within an
hour after administration of a dose and therefore are maximal at 2 to 4 hours, going to persist for a total of 24
hours.

1.2.therapeutic use

Hypertension :, administered as a single tablet or in combination with diuretic medication. With in absent of a
satisfactory treatment outcomes after a little weeks, It is doubtful that daily doses greater than this will carry any
more benefits. A dose smal of 25 mg orally daily can be used for renal-impaired or elderly patients if they have
a clearance of creatinine of less than 15 ml / min or a maximum of 50 mg dose per day when the creatinine
clearance is 15 to 35 ml / min. It t is important to monitor blood pressure before administering a new dose.

Angina Pectoris
The initial dose for adults is tablet 50 mg once per day. If the patient really hasn’t achieved the desired response
after a week, the dosage should be increased to one tablet of 100 mg per day. For optimum therapeutic response
some patients may need 200 mg daily. However, withdrawal should be achieved gradually with the patient
being monitored and advised during this time to limit the physical activity(9)

Acute Myocardial Infarction

Intravenous injection will occur within 12 hours of myocardial infarction as soon as possible after the patient
arrives at the hospital. For an adult, the FDA recommends 5 mg of atenolol over 5 minutes for IV
administration followed by another 5 mg IV injection within 10 minutes. A 50 mg daily treatment, 12 hours
later, should follow. Oral dose can then be either 50 mg twice daily, or 100 mg once a day for 6 to 9 days or
until discharged from the hospPectori

1.3.Adverse Effects
Common side effects involve bronchospasm, bradycardia, diarrhoea, dizziness, constipation, depression,
dyspnoea, heart failure, erectile dysfunction, nausea, weakness, peripheral coldness, rash, sleep disturbances,
syncope, visual impairment, and thrombocytopenia are rare side effects.
Atenolol must not be suddenly interrupted-this can lead to an exacerbation of angina, acute myocardial
infarction or ventricular arrhythmias.Concurrent administration of atenolol with amiodarone, digoxin or
verapamil can cause heart blockage, bradycardia and left ventricular dysfunction.(10)

1.4.Drug Interaction
Can alter the way your drugs work or increase the risk of severe adverse effects. This paper includes not all
potential reactions with the medicines. Keep a list of all your products, and share them with ones doctor and
pharmacist. May not start, stop or change the dosage of any drugs without any of the approval of your doctor
Several drugs that may interfere with this drug usually involve: fingolimod, dolasetron.
Many foods contain additives that might raise your heart rate or blood pressure, or make your heart failure
worse. Ask your pharmacist what drugs you use, and request how to safely utilize them

1.5.Contraindications
Atenolol counterindications include sinus bradycardia, heart block of the second or third degree, cardiogenic
shock, heart failure, severe peripheral arterial disease, and pheochromocytoma. Wiht patients have a history of
bronchospasm asthma, , or other disorders obstructive airway, it must avoided till there not have any
alternative, in which case it may also be administered alongside a bronchodilator
Careful consideration is expected when prescribing to diabetic or thyroid patients as its symptoms that mask the
symptoms of hypoglycemia and thyrotoxicosis-a thyroid storm may also precipitate rapid withdrawal.
Prescribers should exercise caution all through pregnancy-it has been shown that atenolol tries to cross the
placental barrier and is associated with restricting intrauterine growth. The American Academy of Pediatrics
recommends the use during breastfeeding because of a risk of neonatal hypoglycemia and bradycardia(11)

2_Diuretics (Furosemide)

Fig. 5.Furosemide 20 mg tablet Fig. 6 Furosemide 80 mg tablet

2.1. mechanism of Action

Furosemide prevents tubular sodium reabsorption and chloride in the distal and proximal tubules and also in the
thick ascending loop of Henle through inhibiting cotransportation of sodium chloride leading to excessive
excretion of sodium , chloride, magnesium and calcium water(12).
2. 2.therapeutic uses

Fig. 7.Therapeutic uses of furosemide

2.3. adverse effects

The  adverse effects following are that associated to furosemide use(13-17)

Hypokalemia, Hypomagnesemia, Hypocalcemia, Hyperglycemia, Glycosuria, Hyperuricemia,
Hypertriglyceridemia, Increased cholesterol levels, Orthostatic hypotension, Vasculitis,
Thrombophlebitis, Dizziness, Vertigo, Headache, Paresthesia, Hearing impairment, Tinnitus, Dehydration,
Muscle cramps, Abdominal cramping, Anorexia, Constipation or diarrhea, Pancreatitis Hepatic encephalopathy
Anemia, Aplastic anemia, Eosinophilia., Agranulocytosis, Interstitial nephritis Renal injury
Hypersensitivity reactions Anaphylaxis, Skin photosensitivity, Bullous pemphigoid, Erythema multiforme
Exfoliative dermatitis, Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome
Toxic epidermal necrolysis, Urticaria and Fever

2.4. Drug interactions

When your doctor uses this medication to relieve the pain, should be aware of any possible problems with the
medications

Interactions of furosemide with other medications

Amikacin, Amisulpride, Cisapride, Ethacrynic acid, Gentamicin, Kanamycin, Neomycin po, Netilmicin
Paromomycin, Potassium phosphates, iv, Squill, Streptomycin, Tobramycin, Triclofos
2.5.Contraindications

_Application of furosemide ontraindications include patients with a known furosemide allergy and patients
with anuria.
_Body exposure to sunlight probable
Prolonged use induces increased ototoxicity in patients with serious renal deficiency of hypoproteinemia,
concomitant treatment with antibiotics of aminoglycoside, ethacrynic acid or other ototoxic drugs
_When treating severe progressive renal disease
In patients with a prior allergic reaction to sulfonamides, FDA-approved product labeling contraindication;
however, recent studies have suggested that cross-reactivity among both antibiotic sulfonamides and non-
antibiotic sulfonamides is unlikely to happen Electrolyte and acid / base imbalances in cirrhosis can cause
hepatic encephalopathy;
_Large doses of furosemide (greater than 80 mg) can prevent the binding of thyroid hormones to carrier
proteins and leading to a temporary increase in free thyroid hormones, followed by a general decrease in total
thyroid hormone levels
_Hearing loss in neonates was connected with the use of furosemide injection; in premature neonates of
respiratory distress syndrome, diuretic therapy with furosemide may increase the risk of persistent patent ductus
arteriosus (PDA) in the first few weeks of life;
_Blood glucose increases and glucose tolerance test changes
. Furosemide administration might cause acute urinary retention due to higher urine output and urine retention;
_Pregnancy and breastfeeding
When benefits outweigh risks, using furosemide with precaution through pregnancy
Animal studies have demonstrated risk, and no human studies or animal or human studies are possible
Treatment with furosemide all through pregnancy requires fetal growth monitoring because of the risk of
increased fetal birth weights Excretion of furosemide into breast milk; use with caution while breastfeeding; can
inhibit lactatio

3_ ACE inhibitor (Ramipril)

Fig. 8. Ramipril 5 mg tablet

3.1. mechanism of Action

History Physiology: The Renin-Angiotensin – Aldosterone System (RAAS) is a main control mechanism for
blood pressure in the individual body(8,19)
Angiotensinogen is generated mainly in the liver as well as released as a pro-hormone in the bloodstream
Renin is also an enzyme production in response to reduced renal perfusion by the juxtaglomerular cells located
on the afferent arteriole of glomerules.This is a direct result of low blood pressure and signals the production of
renin by juxtaglomerular cells. Renin focuses on the angiotensinogen produced from the liver and cleaves ten
amino acids from its structure , resulting in angiotensin I formation. Angiotensin I tends to increase
vasoconstriction in the blood pressure. As angiotensin I enters the lungs, the angiotensin-converting enzyme
(ACE) which is found in the vascular endothelial cells in the lungs is further converted to angiotensin II.
Angiotensin II: Angiotensin II has many effects which help in optimizing blood pressure. Behaves in the brain,
and rises vasopressin release, that also improves blood pressure by reabsorbing fluids from of the kidneys.
It induces arteriolar vasoconstriction so, by growing total peripheral resistance, increases blood
pressure.Ramipril prevents enzyme-converting angiotensin and reduces formation of angiotensin II. As just a
result, sympathetic activity drops, sodium and water reabsorption from the kidneys decreases, and smooth
muscles also relax in the arterioles. Blood pressure is lowering as a result.

3.2. therapeutic uses

Medically used for following different disease processes

Hypertension: In current clinical practice the most common symptom. Prevention of progression of heart
failure after myocardial infarction ( MI): After MI, Ramipril is used to prevent progression of asymptomatic
heart failure with reduced ejection fraction. Small dose ramipril is often initiated after the confirmed myocardial
infarction within a few hours(20,21)
Reducing risk: Ramipril has been prescribed in patients over 55 years old with a high risk of atherosclerotic
disease and major adverse cardiac events to reduce the risk of MI, stroke , and death.
Symptomatic heart failure to decrease morbidity and mortality with decreased ejection fraction
Other countries may have a few other unlicensed uses.
3. 3.adverse effects

Dry cough: Ramipril inhibits bradykinin degradation in the lung tissues which would be a substrate of
angiotensin-converting enzyme. Dry cough is caused by higher levels of bradykinin. Among patients of Afro-
Caribbean origin this side effect is more common than in other populations. This usually happens within a few
months of diagnosis and stops within one month after the drug has been discontinued
Postural hypotension: a few more patients may develop postural hypotension and might even have fallen as
just a result, resulting in a higher risk of brain injury and bone fracture, particularly in elderly patients.
Dizziness and lightheadedness become associated with postural hypotension if patients abruptly stand up from
the place of sitting or lying. During start of treatment, patients should be given counseling regarding symptoms
of postural hypotension.
Elevated serum creatinine: Ramipril in 1 percent to 2 percent of patients can cause a temporary increase in
serum creatinine.
Hyperkalemia: Hyperkalemia was present in 1 to 10 per cent of patients.
Anxiety-like symptoms: After starting ramipril, patients who are suspected to have anxiety or tremors should be
monitored for these signs for a few weeks at least.
Angioedema: Ramipril may cause angioedema during the course of treatment at any time. It includes either the
head and neck (which may impair the airway) or the intestine.
Other serious side effects include hypoperfusion, disorders of movement, onycholysis and oral disorders

3.4. Drug interactions

A few other products which may interact with such a medication include: aliskiren, other drugs that weaken the
immune system / increase the risk of infection lithium, drugs that may increase potassium levels in the blood
(such as ARBs like losartan / valsartan, drospirenone-containing birth control pills), sacubitril, telmisartan .
A few other products have ingredients which may increase your blood pressure or make your heart failure
worse. Tell owens pharmacist any drugs you are using (especially cough-and-cold drugs, dietary aids, or
NSAIDs such as ibuprofen / naproxen) and how to use them safely.
A very serious reaction may occur if you are getting injections for bee/wasp sting allergy (desensitization) and
are also taking ramipril. Make sure all your doctors know which medicines you are using.
When you get bee / wasp sting allergy (desensitization) injections and are also taking ramipril, a very serious
reaction may occur. Ensure sure that the physicians know what medical products you are using.

3.5. Contraindications 

Hypersensitivity: An important contraindication is hypersensitivity to ramipril, other ACE-i or any component

of the formulation.
Angioedema (hereditary or idiopathic) or a prior history of angioedema following an ACE inhibitor treatment.
(22)
Hyperkalemia: Aldosterone seems to be responsible for potassium excretion in the kidneys. Hence low
aldosterone levels can cause hyperkalemia. Ramipril should be withheld or stopped in patients who develop
hyperkalemia due to its effects on aldosterone production (potassium levels greater than 5 mEq / L)
Pregnancy: Ramipril during pregnancy seems to be absolutely contraindicated. Oligohydramnios and skull
defects have been identified in pregnant women with concomitant use of ACE-i. [English National Formulaire]
Concomitant use has been contraindicated with aliskiren or a neprilysin inhibitor (sacubitril).
The HOPE (Heart Outcome Prevention Study) research performed in 2008 showed that after administering
ramipril 10 mg for 12 weeks, theoretically that there’s no substantial difference in renal function of patients that
had renal artery stenosis .. And Ramipril can be used safely in patients with renal artery stenosis, according to
the HOPE study(23)

Conclosion
Heart failure is a serious clinical problem. Threatens alot of patients specially Eldere people. . HF can be used in
a number of classification schemes. These can be focused on anatomical research result. Usually doctor try to
recognized the symptoms of HF patients to treat them carefully. And we have many classes and families of drug
are used recently to overcome thise clinical syndrome. For example,one of most commen example Beta blocker
is atenolol used to treat hypertension, Angina Pectoris and Acute Myocardial Infarction. Another example
Diuretics (Furosemide) , it is used to treat hyperglycemia but have alot of adverse effects such as Increased
cholesterol levels, and it can causing herring lose and cantraindicated wiht pregnancy women. The last example
is ACE inhibitor (Ramipril).is Prevention the progression of heart failure after myocardial infarction desbit it
has alot of useful advantage but have many adverse effects such as dry cough, hyperkalemia and pregnancy.
Finally when HF Patient see his owen doctor should tell him about having any drug in the current time because
The patient should aware that the Harmful effects of combination.
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