ramipril and Angioedema

The objective of this study was to identify genetic variants associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema.. We carried out a genome-wide association study in 175 individuals with ACE inhibitor-associated angioedema and 489 ACE inhibitor-exposed controls from Nashville (Tennessee) and Marshfield (Wisconsin). We tested for replication in 19 cases and 57 controls who participated in Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET).. There were no genome-wide significant associations of any single-nucleotide polymorphism (SNP) with angioedema. Sixteen SNPs in African Americans and 41 SNPs in European Americans were associated moderately with angioedema (P<10) and evaluated for association in ONTARGET. The T allele of rs500766 in PRKCQ was associated with a reduced risk, whereas the G allele of rs2724635 in ETV6 was associated with an increased risk of ACE inhibitor-associated angioedema in the Nashville/Marshfield sample and ONTARGET. In a candidate gene analysis, rs989692 in the gene encoding neprilysin (MME), an enzyme that degrades bradykinin and substance P, was significantly associated with angioedema in ONTARGET and Nashville/Marshfield African Americans.. Unlike other serious adverse drug effects, ACE inhibitor-associated angioedema is not associated with a variant with a large effect size. Variants in MME and genes involved in immune regulation may be associated with ACE inhibitor-associated angioedema.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Black or African American; Double-Blind Method; Drug Therapy, Combination; ETS Translocation Variant 6 Protein; Genome-Wide Association Study; Humans; Isoenzymes; Neprilysin; Polymorphism, Single Nucleotide; Protein Kinase C; Protein Kinase C-theta; Proto-Oncogene Proteins c-ets; Ramipril; Repressor Proteins; Telmisartan; White People

In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes.. After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.. Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001).. Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).

Topics: Aged; Angioedema; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Pressure; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Ramipril; Risk; Telmisartan

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Coronary Angiography; COVID-19; COVID-19 Nucleic Acid Testing; Drug Substitution; Humans; Male; Middle Aged; Myocardial Infarction; Patient Care Management; Platelet Aggregation Inhibitors; Ramipril; SARS-CoV-2; Treatment Outcome

Angioedema is one of the commonest life-threatening conditions with good outcome timely definitive treatment. However, failure to recognise the common presentation of an uncommon bradykinin-mediated angioedema in time may lead to fatal outcome in the emergency department (ED). We report a case of a 79-year-old male patient who presented to ED with features of ACE inhibitor-induced angioedema which was identified and resuscitated by the emergency physician with use of fresh frozen plasma (FFP) leading to prompt recovery and good outcome.

Topics: Aged; Anaphylaxis; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Humans; Male; Platelet Transfusion; Ramipril

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Glucocorticoids; Heart Failure; Humans; Male; Prednisolone; Ramipril

Angiotensin-converting enzyme (ACE) inhibitors are one of the most used medication among patients with arterial hypertension. In most cases, ACE inhibitors caused side effects are mild; however, from 0.1% to 0.7% of patients can develop life threatening adverse effect, angioedema. Unlike histamine mediated, ACE inhibitor-related angioedema can develop at any time during the treatment course.. An 89-year-old woman with a medical history for arterial hypertension, ischemic heart disease, heart failure, chronic atrial fibrillation developed ACE inhibitor-induced angioedema after 5 years of daily ramipril administration.. Arterial hypertension, ischemic heart disease, heart failure, chronic atrial fibrillation and late onset ACE inhibitor-induced angioedema.. The ACE inhibitor was used for arterial hypertension on a daily basis for the past 5 years. Patient developed airway obstruction requiring intubation. Standard therapy with epinephrine, methylprednisolone and clemastine was administered. Treatment was ineffective, considering that angioedema persisted.. Angioedema resolved after 13 days from the discontinuation of ramipril. Death due to cardiopulmonary insufficiency occurred 24 days after the admission to intensive care unit, despite full clinical resolution of ACE inhibitor-induced angioedema.. Our case highlight the importance of educating clinicians about ACE inhibitor-induced angioedema, as potentially fatal adverse drug reaction. Considering the fact, that no laboratory or confirmatory test exist to diagnose ACE inhibitor-induced angioedema, clinicians' knowledge is the key element in recognition of ACE inhibitor-related angioedema.

Topics: Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Fatal Outcome; Female; Humans; Hypertension; Ramipril

BACKGROUND Bradykinin is an underestimated mediator of angioedema. One subgroup of bradykinin induced angioedema is angioedema triggered by treatment with angiotensin converting enzyme (ACE) inhibitors. Due to its localization in the head and neck region and its unpredictable course, it is a possibly life-threatening condition. There is not an officially approved treatment for ACE inhibitor induced angioedema. CASE REPORT We present a case of an 83-year-old woman, who presented to our ENT department because of acute swelling of the tongue. On admission, there was no pharyngeal or laryngeal edema and no dyspnea. Treatment with glucocorticoids and antihistamines had no response. The patient had ramipril as regular medication, so we assumed ACE inhibitor induced angioedema and treated consequently with C1-inhibitor (human) 1,500 IU. Nevertheless, swelling was progressive and required intubation. Even after the second specific treatment with icatibant, her angioedema subsided extremely slowly. The patient also had regular treatment with saxagliptin, a dipeptidyl peptidase 4 inhibitor, so we assumed that the simultaneous inhibition of two bradykinin degrading enzymes led to a treatment-refractory course of angioedema. CONCLUSIONS General awareness for bradykinin induced angioedema due to regular medication is limited. Our case demonstrated the importance of improving awareness and knowledge about this side effect. We need a better understanding of the pathomechanism to aid in more precise clinical diagnosis. Securing the patient's airway as well as administration of an officially approved therapy is of utmost importance. As the number of patients simultaneously treated with antihypertensive and antidiabetic drugs is likely to increase, the incidence of bradykinin mediated drug induced angioedema is likely to increase as well.

Topics: Adamantane; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Ramipril; Tongue Diseases

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Carotid Artery Diseases; Female; Humans; Ischemic Attack, Transient; Ramipril

Angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE) is the most frequent drug-induced angioedema. The aim of this study was to evaluate potential biomarkers for the detection of the risk to develop an ACEi-AE.. Adult patients who started antihypertensive treatment with ramipril were included and followed up for 4-6 weeks. At baseline, 3 days, and 4-6 weeks after onset of therapy, blood samples were obtained.. Twenty-four patients could be enrolled. The thromboxane values were very heterogeneous, and none of the group differences observed was statistically significant. The values obtained for 6-keto-prostaglandin F1α (6-keto-PGF1α) showed a statistically significant increase with 10 mg/day doses under ramipril therapy.. In this small patient population, it could be shown that determination of 6-keto-PGF1α is feasible. It may prove to be a valuable blood marker for assessing the risk of developing ACEi-AE.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Predictive Value of Tests; Ramipril; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Abdominal Pain; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Female; Humans; Palliative Care; Ramipril

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Humans; Isoenzymes; Neprilysin; Protein Kinase C; Proto-Oncogene Proteins c-ets; Ramipril; Repressor Proteins

We report two cases of ACE inhibitor-associated angioedema and critical airway compromise, where the use of a selective bradykinin 2 receptor blocker resulted in rapid symptom resolution and prevented intubation to protect the airway.

Topics: Aged; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Chlorpheniramine; Diagnosis, Differential; Emergency Service, Hospital; Female; Humans; Male; Nicorandil; Ramipril

Angioedema secondary to the use of ACE-inhibitors is well recognised, with a high rate of airway intervention required. Several treatments have been described, but little evidence exists for any of them. We describe the successful use of fresh frozen plasma in two cases.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Humans; Lisinopril; Male; Middle Aged; Plasma; Ramipril; Tongue

Icatibant is a selective bradykinin 2 receptor antagonist, currently licensed for use in hereditary angioedema. Its benefit in ACE inhibitor angioedema is yet to be fully established. A handful of preliminary case reports suggest that it may be of benefit in reducing both symptom severity and possible hospital or intensive care admission. To date, there are no case reports of the usage of Icatibant in the emergency department in the UK. Here we report our experience of Icatibant in a 62-year-old gentleman presenting with severe oral, pharyngeal and laryngeal oedema while on an ACE inhibitor.

Topics: Adrenergic beta-Antagonists; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Bradykinin B2 Receptor Antagonists; Epiglottis; Humans; Intubation, Intratracheal; Male; Middle Aged; Ramipril; Tongue; Vocal Cords

Topics: Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Glottis; Humans; Male; Neck; Radiography; Ramipril

Topics: Anesthesia, Dental; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Dental Care; Drug Administration Routes; Drug Interactions; Humans; Hypertension; Ramipril

Intake of ACE inhibitors may promote angioedema which can appear months and years after the medication has been stopped. Surgery and local anaesthesia can further aggravate angioedema. A 61-year-old patient with age-related cataract was admitted to our hospital for elective out-patient cataract surgery. A few days after surgery, the patient complained of pain and reduced vision in the operated eye.. Postoperative findings were elevated intraocular pressure (28 mmHg) and a significant reduction of vision. The anterior chamber was shallow. Ophthalmoscopy showed a circumferential choroidal and focal exudative retinal detachment. Local and systemic therapy with antiglaucomatous medications as well as steroids (methylprednisolone) and antibiotics (ciprofloxacin) resulted in control of the eye pressure and an increase of vision. After two weeks, the choroidal detachment disappeared. Important preexisting diseases included a minimal change glomerulonephritis under treatment with low doses of cortisone (4 mg), as well as arterial hypertension. An ACE inhibitor (ramipril) was taken.. ACE inhibitor intake might be associated with choroidal effusion. A preoperative change to another antihypertensive medication should be considered in patients with a tendency to develop angioedema. A glomerulonephritis might also support edema. Patients with such edema should undergo diagnostic evaluation and receive treatment before cataract surgery.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cataract Extraction; Choroid Diseases; Ciprofloxacin; Drug Therapy, Combination; Humans; Hypertension; Male; Methylprednisolone; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome; Ocular Hypertension; Postoperative Complications; Ramipril; Retinal Detachment; Risk Factors

Topics: Angioedema; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Drug Therapy, Combination; Humans; Hypotension; Ramipril; Telmisartan

Topics: Aged; Angioedema; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cardiovascular Diseases; Drug Therapy, Combination; Humans; Hypotension; Ramipril; Risk Assessment; Risk Factors; Telmisartan

C1 esterase inhibitor deficiency is an unusual cause of acute upper airway angioedema. This case of angioedema is secondary to acquired C1 esterase inhibitor deficiency associated with neoplastic disease and triggered by the use of angiotensin converting enzyme inhibitors. It was sufficiently severe to require emergency airway management. A guide to the evaluation and management of angioedema is presented.

Topics: Aged; Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Complement C1 Inhibitor Protein; Female; Humans; Intubation, Intratracheal; Ramipril; Tongue Diseases

Among neuroeosinophilic syndromes, neuromuscular disorders are considered as a special group, including perimyosistis, polymyositis and fasciitis. These three disorders are considered as a continuum. They usually without a recognized cause, and are considered to be spontaneous or exercise-induced. We report the case of a 43 year-old woman who experienced angioedema followed by an histologically proven-fasciitis with eosinophilia after Ramipril (Triatec) use. Causal attribution to Ramipril was considered "plausible". To our knowledge this side effect has never been reported with this drug.

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Drug Eruptions; Eosinophilia; Fasciitis; Female; Humans; Hypertension; Obesity; Ramipril

Angioedema, particularly of the head and neck, is a well-recognized adverse effect of angiotensin-converting enzyme (ACE) inhibitors. Most cases respond to conventional therapy, including antihistamines and corticosteroids. Severe episodes may require epinephrine and intubation.. To report the case of a patient with ACE inhibitor-induced angioedema treated with fresh frozen plasma (FFP).. The patient is a 43-year-old, white woman who first received the ACE inhibitor ramipril in March 2002. After 3 weeks, she developed angioedema of her lips and fingers, which resolved with antihistamines, corticosteroids, and one dose of epinephrine. A low dose of ramipril was restarted 4 days later, which was increased throughout 4 days. In late August 2002, she developed severe upper lip and tongue edema recalcitrant to conventional therapy. Her C1 esterase inhibitor level was normal.. After 4 days of treatment with antihistamines, corticosteroids, epinephrine, antileukotrienes, cyclosporine, and intravenous immunoglobulins, the patient's tongue swelling continued to recur and became more severe. Two units of intravenous FFP was given, with rapid improvement and no further recurrence of tongue swelling.. In our patient, FFP was highly successful in the treatment of resistant, life-threatening angioedema due to an ACE inhibitor. The benefit of FFP in this setting might be due to the effect of kininase II in breaking down accumulated bradykinin.

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Hypertension; Plasma; Ramipril

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Drug Eruptions; Female; Humans; Middle Aged; Ramipril

Angioneurotic edema is a rare (0.1-0.2%) but potentially life-threatening side effect of angiotensin-converting enzyme inhibitors. It can result in serious respiratory distress, airway obstruction and death. Angiotensin-converting enzyme inhibitors associated angioedema is clinically poorly recognized and frequently underestimated condition. A case history of patient with angioneurotic edema due to treatment with ramipril is presented. A 51-year-old man has been sequentially treated for two years with atenolol, indapamide, enalapril, and fosinopril due to primary arterial hypertension. When the treatment was switched to ramipril 5 mg twice a day the fourth dose of the drug was followed by swelling of lips, tongue, and pharynx without symptoms of airway obstruction. Ramipril was discontinued, prednisolone 120 mg and loratidine 10 mg were given. Symptoms of angioedema gradually disappeared. Mechanisms of angioedema are not fully clear. Pharmacological action of angiotensin-converting enzyme inhibitors on bradykinin and substance P, immunological mechanisms and disarrangements in complement system are discussed. Treatment includes immediate withdrawal of angiotensin-converting enzyme inhibitors and acute therapy with epinephrine 0.3-0.5 ml subcutaneous, 50 mg diphenhydramine s/c or i/v, 40-50 mg methylprednisolone. Future treatment with angiotensin-converting enzyme inhibitors is contraindicated.

Topics: Algorithms; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antihypertensive Agents; Diagnosis, Differential; Diphenhydramine; Drug Therapy, Combination; Glossitis; Histamine H1 Antagonists, Non-Sedating; Humans; Hypnotics and Sedatives; Loratadine; Male; Middle Aged; Prednisolone; Ramipril; Time Factors; Treatment Outcome

Angiotensin converting enzyme inhibitors like captopril, enalapril, lisinopril, trandopril and ramipril may rarely induce a life threatening angioedema. We present two cases of severe angioedema induced by enalapril and ramipril along with possible precipitating factors observed in these patients. The importance of prompt recognition and early management of such cases is emphasized.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Epinephrine; Female; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Precipitating Factors; Ramipril; Sympathomimetics

Topics: Angioedema; Humans; Hypertension; Male; Middle Aged; Ramipril