Evidence For A Renal Protective Role In Chronic Heart Failure
The two largest studies of sacubitril/valsartan in patients with HF, the PARADIGM-HF and PARAGON-HF trials, demonstrated positive renal outcomes with sacubitril/valsartan, compared with ACE-I , or ARB ., In PARADIGM-HF in patients with HFrEF, 33% of patients had CKD at baseline. In addition to improving CV outcomes, sacubitril/valsartan was associated with a slower rate of decrease in eGFR, compared with enalapril . During follow-up, the decrease in eGFR was 1.61mL/min/1.73 m2/year with sacubitril/valsartan vs. 2.04mL/min/1.73 m2/year with enalapril , despite a greater increase in urinary albumin/creatinine ratio with sacubitril/valsartan .
Neprilysin inhibition had an incremental benefit on renal function in diabetic patients with HFrEF in PARADIGM-HF. Patients treated with sacubitril/valsartan had a slower rate of decline of eGFR compared with enalapril recipients . The effect was independent of treatment effect on the course of HF or changes in glycated haemoglobin. Furthermore, in PARADIGM-HF, sacubitril/valsartan caused less hyperkalaemia than enalapril and reduced the use of loop diuretics,,, with which there is a dose-dependent association with impaired survival outcomes in patients with advanced HF.
What Are The Possible Side Effects Of Entresto
Entresto may cause serious side effects including:
- See What is the most important information I should know about Entresto? above.
- Serious allergic reactions causing swelling of your face, lips, tongue, and throat that may cause trouble breathing and death. Get emergency medical help right away if you have symptoms of angioedema or trouble breathing. Do not take Entresto again if you have had angioedema while taking Entresto.
- People who are Black and take Entresto may have a higher risk of having angioedema than people who are not Black and take Entresto.
- People who have had angioedema before taking Entresto may have a higher risk of having angioedema than people who have not had angioedema before taking Entresto. See Who should not take Entresto?
- Low blood pressure . Low blood pressure may be more common if you also take water pills. Call your doctor if you become dizzy or lightheaded, or you develop extreme fatigue.
- Kidney problems. Your doctor will check your kidney function during your treatment with Entresto. If you have changes in your kidney function tests, you may need a lower dose of Entresto or may need to stop taking Entresto for a period of time.
- Increased amount of potassium in your blood. Your doctor will check your potassium blood level during your treatment with Entresto.
These are not all the possible side effects of Entresto. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Assessment Of Risk Of Bias And Study Quality
Two trained reviewers independently assessed the quality of the included studies. We used the Cochrane Collaboration’s tool for assessing risk of bias in RCTs. The included RCTs were assessed for random-sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, completeness of outcome data, selective reporting, and other sources of bias. Each domain was assessed as low, unclear, or high risk of bias. The highest risk of bias for any criteria was used to reflect the overall risk of bias for the study .
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Diabetes Mellitus Cardiovascular And Chronic Kidney Diseases
Among all diabetic complications, CVD and chronic kidney diseases are the main culprits for morbidity and mortality . The pathogenesis of diabetes associated CVD and CKD is complex and inter-linked with multiple transmembrane signalling cascades. Initial metabolic insults promoted by underlying genetic predisposition, hyperglycaemia, and hyperinsulinaemia activate neurohumoral stressor systems like the sympathetic nervous system, endothelin system and, the pressor arm of the renin-angiotensin system . The activation of neuro-hormonal systems is one of the consistent features in array of diseases like hypertension, HF, stroke, CVD and CKD, and hence their blockade denotes a key therapeutic strategy in treatment of these diseases. A meta-analysis from various clinical trials for the effects of RAS blockage on diabetes reported that in delaying end-stage renal disease in patients with type 2 diabetes, early RAS interventions are more beneficial than late interventions . However, other clinical studies and meta-analysis have reported that for diabetic patient, treatment with ARB or ACEi do not offer any advantages over other antihypertensive medications . In addition, aldosterone escape and Ang II reactivation have been observed during either ARB or ACEi pharmacotherapy which clinically manifested as copious water and salt retention and reduction in GFR .
Ar Antagonists Renal Impairment
Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Renal Dysfunction
Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system may be at particular risk of developing acute renal failure with these agents. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function with these agents.
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How Does Entresto Work
The two active substances in Entresto, sacubitril and valsartan, work in different ways. Sacubitril blocks the breakdown of natriuretic peptides produced in the body. Natriuretic peptides cause sodium and water to pass into the urine thereby reducing the strain on the heart. Natriuretic peptides also reduce blood pressure and protect the heart from developing fibrosis that occurs in heart failure.
Valsartan is an angiotensin-II-receptor antagonist, which means that it blocks the action of a hormone called angiotensin II. The effects of angiotensin II can be harmful in patients with heart failure. By blocking the receptors to which angiotensin II normally attaches, valsartan stops the hormones harmful effects on the heart and it also reduces blood pressure by allowing blood vessels to widen.
Does Entresto Cause Side Effects
Entresto is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker used to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure . Entresto is combined with other heart failure medications and in place of an ACE inhibitor or other ARBs.
Common side effects of Entresto include
- reduced number of white blood cells,
- reduced number of platelets,
- muscle breakdown, and
- fetal toxicity.
Drug interactions of Entresto include ACE inhibitors, because the combination increases the risk of angioedema and other side effects.
- Combining aliskiren with Entresto increases the risk of kidney failure, high blood potassium, and low blood pressure. Aliskiren should not be combined with Entresto.
- Combining Entresto with potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.
- Increases in blood lithium levels and lithium toxicity have occurred when lithium and ARBs were combined. Blood lithium levels should be monitored if lithium is combined with Entresto.
- Combining Entresto with nonsteroidal anti-inflammatory drugs in patients who are elderly, fluid-depleted , or with poor kidney function may result in reduced kidney function, including kidney failure.
Entresto can cause fetal harm when administered to a pregnant woman.
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Related Publications That Referenced Our Studies
- YavasogluI, I., TurgutkayaII, A., & BolamanIII, Z., “Chlorella-induced thrombocytopenia”, DATA, 2018 Jan .
- Rasmy A, Rahal M, Kisana M, Ahmad S, Salah A, “Morphine induced thrombocytopenia: A case report”, Journal of Case Reports and Images in Oncology, 2015 Dec .
- Onder H, Arsava EM, Arat A, Topcuoglu MA, “Acute middle cerebral artery occlusion treated by thrombectomy in a patient with myelodysplastic syndrome and severe thrombocytopenia”, Journal of vascular and interventional neurology, 2015 Jan .
Sacubitril/valsartan Showed Slowed Kidney Function Decline In Patients With Without Diabetes
The benefit for patients without diabetes was +0.3 ml/min/1.73 m2 per year and for those with concurrent diabetes, the benefit was doubled to +.06 ml/min/1.73 m2.
Milton Packer, MD
In a secondary analysis of the PARADIGM-HF phase 3 trial of sacubitril/valsartan , the therapy was shown to aid in the preservation of kidney function in patients with heart failure with reduced ejection fraction .
Patients with HFrEF that were treated with 97 mg/103 mg twice daily sacubitril/valsartan had a slower rate of decline over the 44-month follow-up period, as measured by estimated glomerular filtration rate than their counterparts treated with 10 mg twice daily enalapril, an ACE inhibitor. For patients with both HFrEF and diabetes, the benefit was doubled.
These results suggest that in addition to the established benefits on heart failure, Entresto treatment also helps to preserve kidney function. This is important because impaired kidney function is associated with poorer outcomes in patients with heart failure, Shreeram Aradhye, MD, the chief medical officer and global head of Medical Affairs at Novartis, said in a statement. The benefit is particularly significant for people with chronic heart failure who also have diabetes, which is an independent risk factor for kidney damage.
When the findings in eGFR were adjusted for urinary cyclic guanosine monophosphate, the incremental benefit for patients with diabetes was no longer clear .
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Financial And Insurance Assistance
If you need financial support to pay for Entresto, or if you need help understanding your insurance coverage, help is available.
Novartis Pharmaceuticals Corporation, the manufacturer of Entresto, offers a program called Entresto Central. This program may help lower the cost of your Entresto prescription. For more information and to find out if youre eligible for support, call 800-245-5356 or visit the program website.
What Are The Side Effects Of Entresto
4.4/5Common side effects of Entresto include:
- low blood pressure ,
Stopping your treatment with Entresto may cause your condition to get worse. Do not stop taking your medicine unless your doctor tells you to.
Furthermore, can Entresto cause kidney problems? Common side effects of Entresto included hypotension, hyperkalemia, and renal impairment, according to the agency. A more serious adverse effect was angioedema. Entresto should not be used with any angiotensin converting enzyme inhibitor, which would increase a user’s risk of angioedema.
Keeping this in view, is coughing a side effect of Entresto?
Cough was a common side effect reported in people who took Entresto. In a study of adults with heart failure, 9% of adults who took Entresto and 13% of adults who took enalapril had a cough. If you have a cough that concerns you while taking Entresto, talk with your doctor.
How long does Entresto stay in your system?
A washout period of 36 hours is required prior to starting Entresto. This means you will need to stop taking all ACE inhibitors or ARBs for 36 hours prior to starting Entresto.
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What If I Miss A Dose
If you miss a dose of Entresto, be sure to take it as soon as you remember. If the timing is too close to your next dose, just take your next scheduled dose. Be sure not to take more than one dose at a time. Taking multiple doses may increase your risk for more side effects. You should speak with your doctor about any missed doses, if youre concerned.
To help make sure that you dont miss a dose, try setting a reminder on your phone. A medication timer may be useful, too.
Changes In Kidney Function During Intercurrent Illness
Regardless of whether patients are treated with RAAS inhibitors, changes in renal function are common during acute intercurrent illness the incidence of AKI is between 7% and 18% of hospitalised patients. AKI is a powerful risk marker for poor outcome and is strongly associated with an increase in the risk of subsequent admission for heart failure. Renal function often does not to return to baseline level in survivors of AKI, especially in those with pre-existing CKD.
The incidence of AKI as defined by hospital coding is rising rapidly, which may reflect a genuine increase or simply greater awareness. Conditions associated with the development of AKI are also common indications for RAAS inhibitors and thus AKI in association with RAAS blockade is a common clinical scenario. However, it is not clear that ACEI/ARB therapy alone is associated with a substantially increased risk of AKI.
In patients on a RAAS inhibitor, intercurrent illness commonly causes AKI, but there is no evidence that stopping the RAAS inhibitor is beneficial.
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If a patient with HFrEF develops hyperkalaemia :
-
Potassium 5.5mmol/L, monitor closely, medication review and consider suspending RAAS inhibitor.
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Potassium 6.0mmol/L, stop RAAS inhibitor.
If the patient with HFrEF has a rise in creatinine during intercurrent illness:
Stop any other medication that may worsen renal function, including diuretic if clinically appropriate.
If by 30%,RAAS inhibitor should be stopped.
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Are There Any Risks
Like all medicines, some patients experience side effects when taking Sacubitril Valsartan. The most common side effect is a fall in blood pressure, which may make you feel light headed, dizzy or faint. This side effect is likely to become less noticeable with time, but if you feel you cannot cope, then please contact the Heart Failure clinic or tell your GP.
Other side effects may include changes in levels of chemicals in your blood and how well your kidneys work. For this reason you must have a blood test 2-4 weeks after starting your new tablets. This will usually be done at your GP surgery or the GP will advise you where it will be undertaken.
Stop taking Sacubitril Valsartan and seek immediate medical attention if you notice any swelling of the face, lips, tongue and/or throat, which may cause difficulties in breathing or swallowing. These may be signs of angioedema .
For more information about cautions, warnings and side effects, please read the patient information leaflet supplied with your medicine.
How Should I Use This Medication
The usual starting dose of sacubitril – valsartan is 1 tablet of 49 mg sacubitril and 51 mg valsartan taken twice a day. Based on the effectiveness of the medication, your doctor will gradually increase the dose to 1 tablet of 97 mg sacubitril and 103 mg valsartan taken 2 times a day.
This medication may be taken with or without food.
Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.
It is important to take this medication exactly as prescribed by your doctor.
If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.
Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.
Do not dispose of medications in wastewater or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.
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Eligibility Criteria And Search Strategy
We searched Medline , Scopus, and Thomson Reuters Web of Science databases to identify the published studies. The inclusion criteria were the following: the clinical trial had to be an RCT the control group had to take a RAS inhibitor the RCT had to report data regarding renal function. We excluded observational studies, case series and case reports, studies published in abstracts, literature reviews, editorials, studies not conducted on humans, and studies on patients aged < 18 years. The main search was run on 9 January 2020 and updated weekly until June 2020. The keywords regarding sacubitril/valsartan and terms related to RCTs were typed in various combinations using Boolean operators . Hand searches of reference lists of articles and relevant literature reviews were used to complement the computer search. The search was limited to English-language studies published in peer-reviewed journals.
Why Is Entresto Approved
The Agencys Committee for Medicinal Products for Human Use decided that Entrestos benefits are greater than its risks and recommended that it be approved for use in the EU. The main study found that Entresto reduced deaths from heart and circulation problems or hospital admissions for heart failure.
Entrestos serious side effects in the main study were similar to those of enalapril, which is already authorised for use in heart failure. Valsartan, one of the active substances in the medicine, is well established for the treatment of high blood pressure and heart failure its side effects are well known.
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Will Entresto Affect My Bnp Level
Yes. Taking Entresto can affect your B-type natriuretic peptide level. BNP is a hormone that your heart makes. Your doctor may check your blood levels of BNP and a related hormone called NT-proBNP to monitor your heart failure.
BNP and NT-proBNP levels typically go up when heart failure worsens. Theyll go down when heart failure is stable. BNP and NT-proBNP dont cause heart failure. Theyre just chemical markers that your doctor uses to check your heart health and your hearts response to Entresto.
Sacubitril, one of the active drugs in Entresto, blocks your body from breaking down BNP. This causes BNP levels to rise when you take Entresto. Sacubitril doesnt block the breakdown of NT-proBNP, though, so NT-proBNP levels will fall when you take Entresto.
Your doctor will factor in Entrestos effects on BNP and NT-proBNP when they review your blood test results.
How Should I Take Entresto
Take Entresto exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.
You may take Entresto with or without food. Take the medicine at the same time each day.
Sacubitril and valsartan doses are based on weight in children. Your child’s dose needs may change if the child gains or loses weight.
If you cannot swallow a tablet whole, a pharmacist can make an oral suspension . Tell the doctor if the person taking this medicine has trouble swallowing the tablet.
Shake the oral suspension before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device .
Your blood pressure will need to be checked often. Your kidney function may also need to be checked.
Store Entresto in the original container at room temperature away from moisture and heat. Throw away any oral suspension not used within 15 days after it was mixed. Do not keep the oral suspension in a refrigerator.
Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.
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