Data Extraction And Quality Assessment
Two authors extracted first author, publication year, comparison, sample size, country, setting , proportion of men, age, maximum follow-up duration from included studies. We used odds ratios with 95% confidence interval for direct evidences or 95% credible intervals for indirect evidences to report dichotomous data. For continuous variable , we applied standardized mean differences with 95% CI for direct evidences or CrI for indirect evidences.
For missing data, we carried out an intention-to-treat analysis if possible.8 For dichotomous data, when the included studies used a perprotocol analysis, we used the data that the studies supplied. We then conducted sensitivity analyses through best-worst scenarios and worst-best scenarios . For continuous data, we only performed the perprotocol analysis.
Cochrane risk of bias tool was put into use to evaluate the risk of bias.9 There were 7 domains in the tool: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias . Two authors independently made judgments about each domain .
What Are Ace Inhibitors
Antihypertensives are medications that lower blood pressure and come in a variety of classes. ACE inhibitors are one class of antihypertensives.
Doctors regularly prescribe ACE inhibitors to treat hypertension. Hypertension, commonly known as high blood pressure, is a severe condition that affects adults in the United States.
ACE inhibitors can also help to treat other conditions like:
- proteinuria, excess protein in the urine
- glomerular diseases, which are conditions that inhibit filtration in the kidneys
- atherosclerosis, a narrowing of arteries due to plaque build up
There are many different medications under the ACE inhibitor classification. The main difference between the types is their duration. Some types of ACE inhibitors are more effective in the short term, while others are more common for long-term treatments.
Common ACE inhibitors include:
Most ACE inhibitors are oral medications. The exception is enalapril, which doctors will administer intravenously.
Efficacy Of Multiple Drug Therapies For Heart Failure With Reduced Ejection Fraction
The use of new therapies as well as multiple drug therapies together has improved the overall prognosis of HFrEF.
Heart failure patients used to be treated with vasodilators and then clinical trials established that ACE inhibitors and angiotensin receptor blockers are crucial aspects for cardiac recovery of patients suffering from HFrEF. These medicines have been shown to reduce morbidity from heart failure and should be administered as the first line of therapy in heart failure patients.
In addition, these studies found that in patients who are being treated with ACE inhibitors and ARBs, adding beta-blockers and mineralocorticoid receptor antagonists to the treatment regimen provides additional benefits.
In recent developments, a study found that the use of angiotensin receptor neprilysin inhibitor in patients was shown to be superior in some circumstances to the traditional pharmaceutical ACE inhibitor usually used, called enalapril.
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Eligibility Criteria And Outcomes Of Interest
We included randomised clinical trials assessing the effect of high-dose versus low-dose ACEIs in adults with chronic HF of any aetiology and reduced left ventricular ejection fraction .
We excluded preclinical studies, observational studies, systematic reviews and meta-analyses, case studies, letters, editorials and conference abstracts.
The outcomes of interest were all-cause mortality, cardiovascular mortality, all-cause hospitalisation, cardiovascular hospitalisation, functional capacity, quality of life and adverse effects. In order to define relevant clinical outcomes, we conducted a literature search and consulted a patient representative. Patients with HF attribute greater value to quality of life than to longevity. Accordingly, patients ascribed higher weight to functional capacity and adverse effects and lower value to hospitalisation and mortality than healthcare professionals.
Effectiveness In Heart Failure
Several major clinical trials have looked at the use of ACE inhibitors in heart failure treatment. They have shown that ACE inhibitors significantly reduce the need for hospitalization, improve survival, and lower the risk of heart attacks. Symptoms of heart failure such as dyspnea and fatigue also improve.
Current guidelines from the American College of Cardiology and the American Heart Association strongly recommend a renin-angiotensin system blocker for those with heart failure with a reduced left ventricular ejection fraction . ACE inhibitors are one of three recommended first-line therapy options.
Other treatment options include angiotensin-receptor neprilysin inhibitors and angiotensin II receptor blockers .
The ACC and AHA now recommend the use of ARNIs over ACE inhibitors in those with mild to moderate heart failure symptoms. However, ACE inhibitors may still be preferred in certain cases.
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The Importance Of Angiotensin Receptor Blockers
Similar to ACE inhibitors, ARBs inhibit the action of angiotensin II in patients with heart failure with reduced ejection fraction. However, instead of preventing the conversion from angiotensin I to angiotensin II, like ACE inhibitors do, ARBs work by blocking angiotensin II from binding to its receptor.
Blocking the action of angiotensin decreases vasoconstriction and relaxes vasculature. However, ARBs do not cause inhibition of kininase as ACE inhibitors do. For this reason, ARBs can be a suitable pharmaceutical therapy for patients who are intolerant of ACE inhibitors.
Its been shown that ARBs have the same result as ACE inhibitors in heart disease therapy they both reduce morbidity. In the 2003 Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity study, ARBs showed great potential in cardiovascular outcomes compared with placebo groups. The study focused on cardiovascular death or hospital admission in patients with symptomatic heart failure with an ejection failure of 40% or less who were intolerant of ACE inhibitors. The outcome shows that 33% of patients who took the ARB therapy had passed away due to cardiovascular causes, compared to 40% in the placebo group.
Reasons For Not Achieving Recommended Doses And Their Effect On Mortality
BIOSTAT specifically recorded reasons for not achieving recommended doses . We divided the patients in three groups: those who reached the recommended dose, those who did not reach the recommended dose because of symptoms, side effects or non-cardiac organ dysfunction, and those who did not reach the recommended dose because of other/unknown/not specified reasons.
Adjusted mortality rate for patients receiving recommended dose reached less than recommended dose due to symptoms, side effects or non-cardiac organ failure and reached less than recommended dose for other reasons, together with the risk set sizes at each time point.
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Heart Failure Research At The Cardiovascular Research And Training Institute
The Investigators in the Nora Eccles Harrison Cardiovascular Research and Training Institute are pioneering the development of new drug therapies for heart failure. Over the past decade, we have been exploring molecular mechanisms underlying genetic dysregulation, proteomics alteration, insufficient energy supply, and metabolic abnormalities of the heart when it fails. By studying the fundamental biology of healthy and failing heart muscle cells, our Investigators are identifying critical molecules that can be targeted for the functional rescue of failing hearts. With many years of extensive research at the bench, researchers in the CVRTI now found two proteins that can be used to treat injured hearts in both acute and chronic settings. GJA1-20k is a stress response protein which helps maintain normal heart rhythms and energy supply. During acute injury, GJA1-20k can maintain myocyte survival, thus limiting heart damage. cBIN1, on the other hand, is a protein organizing the excitation-contraction machinery in heart muscle cells to maintain normal pump function of the heart. A multidisciplinary team has been formed within the CVRTI to use gene transfer methods to deliver exogenous GJA1-20k or cBIN1 to failing hearts. The therapeutic effect of GJA1-20k and cBIN1 gene therapy is currently under advanced preclinical studies and toxicity and safety studies are underway in anticipation of clinical trials.
Other Guidelines For Ace Inhibitors
Never stop taking your medication, even if you feel that it is not working. Your heart failure symptoms may not improve right away when taking ACE inhibitors. But long-term use of ACE inhibitors helps manage chronic heart failure and reduces the risk that it will get worse.
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Risk Of Bias In The Included Studies
The risk of bias is indicated in Figure Figure2.2. For random sequence generation domain, 4 studies were rated as low risk of bias. None described adequate allocation concealment. In terms of blinding of participants and personnel, 5 studies had a low risk of bias. Two studies did not blind to participants and personnel. Considering blinding of the outcome assessment domain, 4 studies were considered as a low risk of bias. Two studies had a high risk of bias in blinding of the outcome assessment. Eighteen studies had a low risk of bias regarding incomplete outcome data domain in contrast, 11 studies were considered as a high risk of bias. All studies had an unclear risk of bias with regard to selectively in reporting results. Seven studies had a high risk of bias in other biases domain .
Risk of bias of all included studies.
Ace Inhibitors In The Treatment And Prevention Of Heart Failure
IntroductionSince their introduction in the mid-1980s, angiotensin converting enzyme inhibitors have become well established for the treatment of hypertension and heart failure. In addition, they slow progression of renal impairment in diabetic nephropathy. There have now been several major studies investigating the role of ACE inhibitors in heart failure including the SAVE, SOLVD and AIRE studies.
BenefitsACE inhibitors improve survival in heart failure when added to conventional treatment. The greatest benefit is seen in those patients with the most severe heart failure. A smaller benefit is seen in patients with mild-to-moderate heart failure. However, despite the improved survival, the prognosis of moderate-to -severe heart failure remains poor. Nevertheless, largely because of the potential survival benefit, most cardiologists now believe that an ACE inhibitor should be added to diuretic therapy in all patients with overt heart failure, even if the heart failure is only mild. Some physicians prescribe ACE inhibitors before diuretics, although there is no trial-based evidence for this approach.
The benefits of treatment are not restricted to survival. The addition of an ACE inhibitor to diuretic therapy improves the control of heart failure, an important symptomatic benefit. This reduces the need for hospitalisation and probably improves the patient’s quality of life. There may also be economic benefits for the health care system.
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Ace Inhibitors In Congestive Heart Failure
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Can Pregnant People Take Them
Due to the risk of side effects, doctors typically ACE inhibitors to pregnant people.
Studies show that exposure to ACE inhibitors during pregnancy embryo and fetus development and increase the risk of adverse health outcomes in pregnant persons.
Doctors can to ACE inhibitors for those planning a pregnancy. Some medical professionals advise that people of childbearing age avoid the use of ACE inhibitors altogether.
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Risk Of Bias And Quality Assessment
Two independent reviewers critically appraised the included studies using RoB 2.0. The overall quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Discrepancies in quality assessment were resolved through consensus or by a third reviewer.
Ace Inhibitors And Arbs A Cornerstone In The Prevention And Treatment Of Cardiovascular Disease
Prof. Héctor Bueno ,FESC
Dr. Michael Mcintosh
ACE inhibitors and ARBs act by blocking RAAS with beneficial effects on patients with cardiovascular risk factors only and with several heart diseases . When indicated, they should be started at low dose and increased gradually to reach the target dose. ACE inhibitors and ARBs share indications, contraindications and most side effects . Monitoring of the renal function and serum potassium is needed to reduce the incidence of renal insufficiency and hyperkalaemia during treatment, particularly when initiated or uptitrated.
The activation of the renin-angiotensin-aldosterone system plays a key role in the development and progression of cardiovascular disease, especially in arterial hypertension, heart failure and coronary artery disease. ACE inhibitors are the most used and studied type of RAAS blocker and their benefits are due to their neurohormonal modulatory effects, which have vasodilatory, anti-inflammatory, plaque-stabilizing, antithrombotic and anti-proliferative effects.
ARBs have similar pharmacological properties to ACE inhibitors but may be better tolerated as coughing is not a frequent adverse effect. As ARBs are more expensive and have not shown any additional clinical benefits over ACE inhibitors, they are usually considered as an alternative for ACE inhibitors intolerant patients.
ACE inhibitors and ARBs share most indications and contraindications:
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How Should I Take Them
Usually on an empty stomach, an hour before meals. Follow the directions on the label about how often to take it. The number of doses you take each day, the time between them, and how long youâll need to take it will depend on the type of ACE inhibitor youâre prescribed, and your condition.
While taking them, have your doctor check your blood pressure and kidney strength regularly.
Never stop taking an ACE inhibitor without first discussing with your doctor. If youâre taking them for heart failure, your symptoms may not improve right away. However, long-term use helps manage chronic heart failure and lessen the chance that your condition will get worse.
Will My Ace Inhibitor Interact With Any Foods Or Drugs
It may. Donât use salt substitutes unless your doctor or nurse approves. Some contain potassium, and since ACE inhibitor medications cause the body to retain potassium, it can be dangerous to your health. Read food labels to choose foods low in salt and potassium. A dietitian can help, too.
Over-the-counter nonsteroidal anti-inflammatory medications and aspirin may cause your body to retain salt and water, and decrease the effect of an ACE inhibitor. Check with your doctor before taking any anti-inflammatories.
Itâs important for your doctor to know about all the drugs you are taking. Some, in addition to those above, may not work well with ACE inhibitors.
Talk to your doctor before taking any new medicines, including over-the-counter drugs, herbs, and supplements.
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Can Pregnant Women Take Them
Women should not take them during pregnancy, especially during the second and third trimesters. They can lower blood pressure and cause kidney failure or high potassium levels in the blood of the mother. They can cause death or deformity in the newborn.
Babies shouldnât be breastfed if the mother is taking an ACE inhibitor. The medicine can pass through breast milk.
Ace Inhibitor Drug Names
Several ACE inhibitors are on the market, and it is generally thought that they are equally beneficial in the treatment of heart failure. Commonly used ACE inhibitors include:
When first prescribed, ACE inhibitors usually are started at a low dose, and the dosage is gradually increased to the target dosage. Gradually increasing the dosage helps prevent adverse effects. If the higher doses are not tolerated well, treatment is usually continued at a lower, better-tolerated dose.
Most experts believe that lower doses of ACE inhibitors are nearly as effective as higher doses, but higher doses are preferred because they have been formally tested in clinical studies.
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Higher Versus Lower Doses Of Ace Inhibitors Angiotensin
Roles Formal analysis, Writing original draft, Writing review & editing
Affiliation Division of Cardiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Roles Methodology, Writing review & editing
Affiliation Department of Family Medicine, University of Alberta, Edmonton, Alberta, Canada
Predictors For Lower Dose
Independent predictors for achieving lower percentages of recommended ACE-inhibitor/ARB dose were female sex, country of inclusion, lower BMI and eGFR, and higher alkaline phosphatase values. Predictors for lower beta-blocker doses were higher age, country of inclusion, lower heart rate and diastolic blood pressure , and more signs of congestion . When the different types of hospitals participating in BIOSTAT-CHF , or sites as independent predictors were added to the different models, country differences remained significant.
Average percentage achieved of the recommended dose of ACE-inhibitor/ARB , and beta-blocker per country.
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Enhancing Healthcare Team Outcomes
ACE inhibitors are one of the most widely used drugs for hypertension and heart failure, but their popularity does not mean they do not require the management of an interprofessional team. Besides nephrologists and cardiologists, these drugs are widely prescribed by nurse practitioners and primary care providers. While ACE inhibitors are relatively safe, a pharmacist should examine the patient’s medication record to verify dosing and check for drug-drug interactions. Nursing can provide patient counsel, monitor for interactions and adverse events, and report any issues to the prescriber. It is important to monitor renal function and levels of electrolytes regularly. Because many ACE inhibitors are currently available, it is important to keep up with the guidelines and recommendations, and the pharmacist can help the prescriber in this area. An interprofessional team approach will optimize ACE inhibitor therapy resulting in improved patient outcomes.