Atherosclerotic stenosis or occlusion of the coronary arteries is eliminated in various ways, one of which is stenting of the heart vessels. This technique allows you to expand the lumen of the arterial bed by fixing a stent in it in the form of a cylindrical mesh structure. It is produced on the basis of biocompatible materials (metal, alloys or polymers). By supporting the vascular wall, the stent helps restore the internal diameter of the vessel and its hemodynamics. This is extremely important for restoring coronary blood flow and ensuring complete myocardial trophism.
To avoid thrombus formation and re-stenosis, in addition to the use of structures coated with antithrombotic substances (heparin, nanocarbon, phosphorylcholine, etc.), it is important to use a number of drugs, including Brilinta. Drug therapy at the postoperative stage allows for stable blood thinning and the formation of blood clots in the arterial beds. How much Brilinta to drink after stenting, as well as the features of the postoperative period, will be discussed further.
What is Brilinta
Brilinta is a modern drug with the active substance ticagrelor, which can interact with adenosine diphosphate blockers. Indicated for adults to prevent atherothrombotic complications. Including patients with a history of a heart attack one year or more ago. The medication reduces the incidence of thrombosis in blood vessels, the risk of repeated heart attacks, ischemic strokes and mortality from cardiovascular diseases by 15-20%. Usually prescribed with small doses of aspirin. Clinical effectiveness has been confirmed by several studies.
The drug is produced in the form of tablets with different dosages. They are easy to swallow with clean water. If the patient has problems swallowing, it is possible to crush the pill to a powder.
Brilinta®
Security Profile at a Glance
The safety profile of Brilinta® was studied in two large outcome studies (PLATO and PEGASUS), which involved more than 39,000 patients (see section "Pharmacodynamics").
In the PLATO study, patients receiving Brilinta® were more likely to discontinue therapy due to adverse events than patients receiving clopidogrel (7.4% versus 5.4%). In the PEGASUS study, patients receiving Brilinta® had a higher rate of discontinuation due to adverse events than patients receiving ASA monotherapy (16.1% in the ticagrelor 60 mg plus ASA group and 8.5% in the ASA monotherapy). The most common adverse events in patients taking ticagrelor were bleeding and shortness of breath. The following are the adverse reactions noted in these studies.
List of adverse reactions
Adverse reactions noted in clinical studies of Brilinta® are distributed by organ system class and frequency of development.
The frequency of adverse reactions is determined using the following categories: very often (≥1/10), often (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rarely (≥1/100). 10000, <1/1000), very rare (<1/10000), unspecified frequency (cannot be estimated from the data obtained).
Benign, malignant and unspecified neoplasms (including cysts and polyps)
: uncommon - bleeding from a tumor2.
From the hematopoietic and lymphatic systems:
very often - bleeding associated with a blood disorder3.
Metabolic and nutritional disorders
: very often - hyperuricemia1; often - gout.
Mental disorders:
infrequently - confusion.
From the nervous system
: often - dizziness, fainting; infrequently - intracranial hemorrhage.
From the side of the organ of vision:
infrequently - hemorrhage in the eye4.
On the part of the hearing organ:
often - vertigo; infrequently - hemorrhage in the ear.
From the cardiovascular system:
often - arterial hypotension.
From the respiratory system:
very often - shortness of breath; often - bleeding from the respiratory system5.
From the gastrointestinal tract:
often - gastrointestinal bleeding6, diarrhea, nausea; infrequently - retroperitoneal bleeding.
From the skin and subcutaneous tissue:
often - subcutaneous or cutaneous hemorrhage7, skin itching.
From the musculoskeletal system:
infrequently - hemorrhage into the muscles8.
From the urinary system:
often - bleeding from the urinary tract9.
From the reproductive system and mammary glands:
infrequently - bleeding from the genital tract10.
Laboratory and instrumental data
: often - increased creatinine concentration in the blood1.
Injuries, intoxications and complications of manipulations
: often - bleeding after manipulation, traumatic bleeding11.
1—The frequency of laboratory abnormalities (increased uric acid concentration above the upper limit of normal from a baseline value that was within the normal range or less than the lower limit of normal; increased creatinine concentration > 50% of the baseline value) is reported rather than the frequency of reports of adverse events.
2 - For example, bleeding from a tumor (cancer) of the bladder, from a tumor (cancer) of the stomach, from a tumor (cancer) of the colon.
3 - For example, a tendency to bruise, spontaneous hematoma, hemorrhagic diathesis.
4 - For example, conjunctival, retinal, intraocular hemorrhage.
5 - For example, epistaxis (nosebleeds), hemoptysis.
6 - For example, bleeding from the gums, rectal bleeding, bleeding from stomach ulcers.
7- For example, ecchymosis, skin hemorrhage, petechiae.
8- For example, hemarthrosis, hemorrhage into the muscle.
9- For example, hematuria, hemorrhagic cystitis.
10- For example, vaginal bleeding, hematospermia, postmenopausal bleeding.
11- For example, bruise, traumatic hematoma, traumatic bleeding.
Description of some adverse reactions
Bleeding
The following definitions of bleeding were used in the PLATO and PEGASUS studies:
— Major lethal/life-threatening bleeding according to PLATO definition:
lethal, or any intracranial hemorrhage, or bleeding into the pericardial cavity with cardiac tamponade; or hypovolemic shock or severe hypotension caused by bleeding and requiring the use of vasoconstrictors/inotropes or surgery, or clinically overt bleeding accompanied by a decrease in hemoglobin concentration of more than 50 g/L, or a transfusion of 4 or more units of red blood cells.
- Major other bleeding according to PLATO definition:
causing significant disability of the patient, or clinically obvious bleeding, accompanied by a decrease in hemoglobin level by 30-50 g/l, or requiring transfusion of 2-3 units of whole blood or red blood cells.
— Minor bleeding according to PLATO definition:
requires medical intervention to stop or treat bleeding.
- Major bleeding according to TIMI definition:
lethal, or any intracranial hemorrhage, or clinically overt bleeding associated with a decrease in hemoglobin concentration of 50 g/L or more, or, if hemoglobin concentration data are not available, a decrease in hematocrit of 15%.
- Major other bleeding according to TIMI definition:
non-fatal, non-intracranial major bleeding as defined by TIMI.
— Minor bleeding according to TIMI definition:
clinically obvious bleeding, accompanied by a decrease in hemoglobin level by 30-50 g/l.
— Bleeding requiring medical intervention, as defined by TIMI
: Requires medical intervention or results in hospitalization or emergency evaluation.
- Lethal bleeding:
leads to the death of the patient within 7 days.
Data on bleeding events in the PLATO studies (Kaplan-Meier estimate (%) at 12 months)
Brilinta® and clopidogrel did not differ in the incidence of major bleeding overall according to PLATO criteria (11.6% and 11.2%, respectively), or fatal/life-threatening bleeding according to PLATO criteria (5.8% in both groups). However, the incidence of combined major and minor bleeding according to PLATO criteria was higher in the ticagrelor group (16.1%) compared with clopidogrel (14.6%, p = 0.0084). There were several cases of fatal bleeding: 20 (0.2% of patients) in the ticagrelor group and 23 (0.3% of patients) in the clopidogrel group.
Age, sex, weight, race, geographic region, comorbidities, concomitant medications, and medical history, including previous stroke and transient ischemic attack, did not affect the incidence of overall and nonprocedure-related major bleeding according to PLATO criteria. No groups were identified with an increased risk of bleeding.
Bleeding associated with CABG:
In the PLATO study, 42% of 1584 patients (12% of the cohort) undergoing CABG experienced major fatal/life-threatening bleeding, with no significant difference in either treatment group. Fatal bleeding associated with CABG surgery occurred in 6 patients in each treatment group (see section "Special Instructions").
Non-CABG
and non-procedure-related bleeding:
Brilinta® and clopidogrel did not differ in the incidence of major fatal/life-threatening non-CABG bleeding according to PLATO criteria, but Brilinta® was more likely to experience major bleeding in patients with non-CABG procedures. overall according to the PLATO study definition (4.5% versus 3.8%; p=0.0264). When removing procedure-related bleeding events, there were more bleeding events in the ticagrelor group (3.1%) than in the clopidogrel group (2.3%; P = 0.0058). Discontinuation due to non-procedure-related bleeding was more common with ticagrelor (2.9%) compared with clopidogrel (1.2%, p < 0.001).
Intracranial hemorrhage:
More non-procedure-related intracranial bleeding occurred in the ticagrelor group (n=27 bleedings in 26 patients, 0.3%) than in the clopidogrel group (n=14 bleedings, 0.2%), of which 11 bleedings occurred on ticagrelor and 1 on clopidogrel were fatal. However, there was no significant difference in the total number of fatal bleeding events.
Data on bleeding events in the PEGASUS study (Kaplan-Meier estimate (%) at 36 months)
In the PEGASUS-TIMI 54 study, major bleeding as defined by TIMI occurred more frequently with Brilinta® 60 mg twice daily (2.3%) than with ASA monotherapy (1.1%). There was no increased risk of fatal bleeding; There was only a slight increase in the incidence of intracranial hemorrhage (0.6%) compared with ASA monotherapy (0.5%). Several cases of fatal bleeding were noted: 11 (0.3%) in the Brilinta® 60 mg group and 12 (0.3%) in the ASA monotherapy group. The increased risk of major TIMI bleeding with Brilinta 60 mg was primarily due to a higher incidence of other TIMI bleeding due to gastrointestinal events.
With the use of Brilinta® 60 mg, an increase in the frequency of major or minor bleedings according to the TIMI definition was noted (3.4% when using the drug Brilinta® 60 mg compared to 1.4% with ASA monotherapy), major bleedings according to the PLATO definition (3. 5% versus 1.4%) and major or minor bleeding as defined by PLATO (15.2% versus 6.2%).
Discontinuation of therapy due to bleeding was more common with Brilinta 60 mg than with ASA monotherapy (6.2% and 1.5%, respectively). Most of these bleeds were less severe (classified as bleeds requiring medical attention, as defined by TIMI), such as epistaxis, bruising, and hematomas.
The profile of TIMI major bleeding, TIMI major or minor bleeding, and PLATO major bleeding with Brilinta 60 mg was comparable across several prespecified subgroups (eg, age, sex, weight, race, geographic region , concomitant diseases, concomitant medications and medical history).
Intracranial hemorrhage:
Spontaneous intracranial hemorrhage was noted with a similar frequency when using Brilinta® 60 mg and ASA monotherapy (13 cases, 0.2% in each treatment group). The incidence of intracranial hemorrhage due to trauma or procedure was slightly higher in the Brilinta 60 mg group (15 cases, 0.2%) compared with ASA monotherapy (10 cases, 0.1%). There were 6 fatal intracranial hemorrhages when taking Brilinta® 60 mg and 5 lethal intracranial hemorrhages when taking ASA monotherapy. The incidence of intracranial hemorrhage was low in both treatment groups, given the significant comorbidities and cardiovascular risk factors in the study population.
Dyspnea
In the PLATO study, adverse events of dyspnea (dyspnea, dyspnea at rest, dyspnea on exertion, paroxysmal nocturnal dyspnea, and nocturnal dyspnea) occurred in 13.8% of patients receiving Brilinta 90 mg twice daily and in 7. 8% of patients taking clopidogrel 75 mg once daily. The researchers estimated that 2.2% of patients in the ticagrelor group had treatment-related shortness of breath.
Most cases of shortness of breath were mild or moderate in intensity and often resolved without discontinuation of therapy. Typically, shortness of breath developed at the beginning of therapy and in 87% of patients it occurred as a single episode. Dyspnea as a serious adverse event was reported in 0.7% of patients receiving ticagrelor and in 0.4% of patients receiving clopidogrel.
Patients who developed dyspnea were older and often had dyspnea, chronic heart failure, COPD or bronchial asthma before starting ticagrelor therapy.
Data from the PLATO trial suggest that higher rates of shortness of breath with Brilinta are not associated with the development of new or worsening heart or lung disease.
Brilinta® does not affect respiratory function parameters (see section “Special instructions”).
In the PEGASUS study, shortness of breath was observed in 14.2% of patients receiving Brilinta 60 mg twice daily and in 5.5% of patients receiving ASA monotherapy. As in the PLATO study, most cases of dyspnea were mild to moderate (see section "Special Instructions").
Post-marketing use
Below are the adverse reactions that were noted during post-marketing use of Brilinta®. Because reports are obtained spontaneously from a population of unknown size, it is not always possible to reliably estimate the incidence of development.
Immune system disorders:
hypersensitivity reactions, including angioedema (see section "Contraindications").
Disorders of the skin and subcutaneous tissues:
skin rash.
Also, when using the drug Brilinta®, the following were noted:
- undesirable reactions, the connection of which with taking the drug cannot be excluded taking into account the mechanism of action of ticagrelor: thrombocytopenia, immune thrombocytopenic purpura, thrombocytosis, coagulopathy, pulmonary embolism;
- undesirable reactions, probably representing manifestations of hypersensitivity to the drug: urticaria, dermatitis;
- undesirable reactions, the connection of which with the use of the drug has not been established: hemoconcentration, increased hematocrit, decreased hemoglobin, anxiety, restlessness, insomnia, headache, ischemic stroke, tremor, aphonia, dysphonia, tachycardia, bradycardia, arterial hypertension, chest pain, disorders heart rhythm (including atrial fibrillation, ventricular extrasystole), cardiac conduction disturbances (including 2nd degree atrioventricular block), peripheral edema, cough, asthma, bronchospasm, gastritis (including erosive), stomach ulcer, epigastric pain , dyspepsia, pancreatitis, acute renal failure, arthralgia, myalgia, asthenia, malaise, increased concentration of bilirubin in the blood.
How does Brilinta work?
Thanks to the action of the active substance, the likelihood of blood clots is reduced. As a result, the risk of developing severe cardiovascular pathologies is significantly reduced. Another effect that ticagrelor shows in Brilinta is the production of adenosine. It reduces tension in blood vessels and slows down cell death (apoptosis) inside cardiac tissue. If you take this drug regularly, your adenosine levels will increase, which will lead to a longer lasting therapeutic effect.
The medicine is well tolerated in many cases, but it is impossible to completely eliminate the risk of adverse reactions. Often patients have to deal with:
- difficulty breathing;
- bleeding from the nose;
- gastrointestinal bleeding;
- subcutaneous hematomas.
In more rare cases, it is possible to develop:
- tingling in the arms and legs;
- problems with concentration;
- disorientation in space;
- constipation;
- swelling of the face.
Brilinta, 56 pcs., 90 mg, film-coated tablets
Risk of bleeding
In patients with acute coronary syndrome treated with Brilinta® and acetylsalicylic acid, there was an increased risk of non-CABG major bleeding and bleeding requiring increased medical attention, such as major + minor bleeding according to the PLATO
, but the risk of fatal/life-threatening bleeding did not increase (see "Side effects").
When prescribing Brilinta®, the balance between the benefit of preventing atherothrombotic events and the risk in patients with an increased risk of bleeding should be assessed.
If clinically indicated, Brilinta® should be used with caution in the following patient groups:
- patients are predisposed to the development of bleeding (for example, due to recent trauma, recent surgery, bleeding disorders, active or recent gastrointestinal bleeding). The use of Brilinta® is contraindicated in patients with active pathological bleeding, a history of intracranial hemorrhage, or moderate or severe liver failure;
- concomitant use of drugs that may increase the risk of bleeding (for example, NSAIDs, oral anticoagulants and/or fibrinolytics taken within 24 hours before taking Brilinta®).
There is no data on the hemostatic effectiveness of platelet transfusions when using Brilinta®; Brilinta® may inhibit transfused platelets in the blood. Since the concomitant use of Brilinta® and desmopressin did not reduce the standardized bleeding time, it is unlikely that desmopressin will effectively stop bleeding.
Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and/or recombinant factor VIIa may enhance hemostasis. Once the cause of the bleeding has been established and it has been stopped, therapy with Brilinta® can be resumed.
Surgical operations
Before a planned operation or starting to take new medications, the patient should inform the doctor that he is taking Brilinta®.
In patients undergoing CABG, the incidence of major bleeding with Brilinta® was the same as with clopidogrel on all days after discontinuation of therapy, except the first day, when the incidence of major bleeding was higher with Brilinta® (see " Side effects").
If the patient is undergoing elective surgery and the antithrombotic effect is undesirable, then therapy with Brilinta® should be discontinued 7 days before surgery.
Patients at risk of developing bradycardia
Due to the identification of largely asymptomatic pauses in a previous clinical study, patients at increased risk of developing bradycardia (eg, patients without a pacemaker diagnosed with sick sinus syndrome, 2nd or 3rd degree AV heart block, syncope associated with bradycardia) were not were included in the main study to evaluate the safety and effectiveness of Brilinta®. Therefore, due to limited clinical experience with the drug in these patients, it is recommended to prescribe Brilinta® with caution to such patients (see “Pharmacodynamics”).
Additional precautions should be taken when using Brilinta® together with drugs that can cause bradycardia. However, no clinically significant side effects were observed when used together with one or more drugs that can cause bradycardia (for example, 96% - beta-blockers, 33% - CCBs, including diltiazem and verapamil, and 4% - digoxin) (see “Interactions”) ").
In a substudy using 24-hour Holter ECG monitoring, more patients in the acute phase of acute coronary syndrome (ACS) had ventricular pauses >3 s in the ticagrelor group compared with clopidogrel. An increase in the number of ventricular pauses recorded using 24-hour Holter monitoring while taking ticagrelor was observed more often in patients with chronic heart failure compared to the general population in the acute phase of ACS, but not in the first month. Pauses in these patients were not accompanied by subsequent undesirable clinical consequences (syncope and pacemaker installation).
Dyspnea
Shortness of breath when using Brilinta®, usually mild or moderate in intensity, often resolves as drug therapy is continued. Patients with bronchial asthma/COPD may have an increased absolute risk of shortness of breath while taking Brilinta® (see “Side Effects”). In patients with asthma/COPD, ticagrelor should be used with caution. The mechanism of shortness of breath while taking ticagrelor is not clear. If the patient develops a new episode of shortness of breath, shortness of breath persists or worsens while using Brilinta®, then a full examination should be carried out, and in case of intolerance, the drug should be discontinued.
Increased creatinine levels
When taking Brilinta®, creatinine levels may increase (see “Side effects”). The mechanism of this effect is unknown. Renal function should be assessed one month after starting the drug and thereafter in accordance with routine clinical practice, paying particular attention to patients 75 years of age and older, patients with moderate or severe renal impairment and those receiving angiotensin receptor antagonist therapy.
Increased uric acid levels
Patients taking ticagrelor had a higher risk of hyperuricemia than those taking clopidogrel (see "Side effects"). Caution should be exercised in patients with a history of hyperuricemia or gouty arthritis. As a preventive measure, the use of ticagrelor should be avoided in patients with hyperuricemic nephropathy.
Other
Based on the observed interaction between the maintenance dose of acetylsalicylic acid and the effectiveness of ticagrelor compared with clopidogrel, co-administration of a high maintenance dose of acetylsalicylic acid (more than 300 mg) and Brilinta® is not recommended (see Pharmacodynamics, Contraindications, Precautions
).
The combined use of Brilinta® with strong CYP3A4 inhibitors (for example, ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir) is contraindicated (see “Contraindications”), because it may lead to a significant increase in exposure to Brilinta® (see “Interactions”).
Concomitant use of Brilinta® with strong CYP3A4 inducers (for example, rifampicin, dexamethasone, phenytoin, carbamazepine and phenobarbital) is not recommended, because Taking them together may reduce the exposure and effectiveness of ticagrelor (see Interactions).
The combined use of Brilinta® and CYP3A4 substrates with a narrow therapeutic index (for example, cisapride and ergot alkaloids) is not recommended, because Ticagrelor may increase the exposure of these drugs.
The combined use of Brilinta® with simvastatin or lovastatin at a dose of more than 40 mg is not recommended (see “Interaction”).
When using digoxin and Brilinta® together, careful clinical and laboratory monitoring (heart rate and, if clinically indicated, also ECG and digoxin concentration in the blood) is recommended.
There are no data on co-administration of ticagrelor with potent P-gp inhibitors (eg verapamil, quinidine and cyclosporine), which may increase ticagrelor exposure. If their combined use cannot be avoided, it should be used with caution (see “Contraindications”, With caution
, "Interaction").
Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.
There have been no studies of the effect of Brilinta® on the ability to drive vehicles and operate machinery. Brilinta® does not affect or only slightly affects the ability to drive vehicles and operate machinery. Dizziness and confusion have been reported during treatment for acute coronary syndrome. In case of development of these phenomena, patients should be careful when driving a car and other mechanisms.
Brilinta for heart attack prevention
Brilinta is used not only for stenting, but also against the background of problems with blood supply to the heart and the threat of myocardial infarction. Or as an adjunct to drug therapy after balloon angioplasty.
The drug is rational to use, since a sudden obstruction to the normal flow of blood in the branches of the coronary artery is the direct cause of a heart attack. Blood clots are to blame in 95–97% of cases.
A loading dose of Brilinta is not prescribed to patients in the case of heart attack prevention. Typically the daily dose is 120 mg/day, divided into 2 doses. If the patient has previously taken other medications, a daily break is necessary. The exact treatment regimen and dosage is determined by the attending physician.
Brilinta tablet p/o 90 mg N168 (AstraZeneca)
Risk of bleeding When prescribing Brilinta®, the balance between the benefits of preventing atherothrombotic events and the risk in patients with an increased risk of bleeding should be assessed. When clinically indicated, Brilinta® should be used with caution in the following patient groups: - Patients predisposed to bleeding (eg, due to recent trauma, recent surgery, bleeding disorders, active or recent gastrointestinal bleeding). The use of Brilinta® is contraindicated in patients with active pathological bleeding, a history of intracranial hemorrhage, or moderate or severe liver failure. - Concomitant use of drugs that may increase the risk of bleeding (for example, non-steroidal anti-inflammatory drugs, oral anticoagulants and/or fibrinolytics taken within 24 hours before taking Brilinta®). In a study in healthy volunteers, platelet transfusion did not reverse the antiplatelet effect of Brilinta and is likely to have no clinical effect in bleeding patients. Since the concomitant use of Brilinta® and desmopressin did not reduce the standardized bleeding time, it is unlikely that desmopressin will effectively stop bleeding (see section “Interaction with other drugs and other types of drug interactions”). Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and/or recombinant factor VIIa may enhance hemostasis. Once the cause of the bleeding has been established and it has been stopped, therapy with Brilinta® can be resumed. Surgery Before scheduled surgery or starting new medications, the patient should inform the doctor that he is taking Brilinta®. In the PLATO study, in patients undergoing CABG, there was more bleeding with Brilinta compared with clopidogrel when therapy was stopped one day before surgery, but the incidence of major bleeding was similar when therapy was stopped 2 or more days before surgery. in the ticagrelor and clopidogrel groups (see section “Side effects”). If the patient is undergoing elective surgery and the antithrombotic effect is not desired, then therapy with Brilinta® should be discontinued 7 days before surgery (see section “Pharmacological properties”). Patients with previous ischemic stroke Patients with ACS (acute coronary syndrome) with a previous ischemic stroke can take Brilinta® for up to 12 months (PLATO study). The PEGASUS trial did not include patients with a history of myocardial infarction with a previous ischemic stroke. Therefore, in the absence of data, therapy for more than 1 year should be carried out with caution. Patients with liver failure The use of Brilinta® is contraindicated in patients with severe liver failure (see sections “Contraindications” and “Dosage and Administration”). Caution should be exercised in patients with moderate hepatic impairment, given the limited experience with the drug in patients in this group (see sections “Pharmacokinetics” and “Dosage and Administration”) Patients at risk of developing bradycardia Due to the detection in a previous clinical study mostly asymptomatic ventricular pauses, patients with an increased risk of developing bradycardia (eg, patients without a pacemaker diagnosed with sick sinus syndrome, 2nd or 3rd degree atrioventricular heart block, or syncope associated with bradycardia) were not included into the main study to evaluate the safety and effectiveness of Brilinta®. Therefore, due to limited clinical experience with the use of the drug in these patients, it is recommended to prescribe Brilinta® to them with caution (see section “Pharmacological properties”). Caution should also be exercised when using Brilinta® together with drugs that can cause bradycardia. However, in the PLATO study, there were no clinically significant adverse effects when coadministered with one or more drugs that can cause bradycardia (eg, 96% of patients were concomitantly taking beta-blockers, 33% were taking calcium channel blockers, including diltiazem and verapamil, and 4% — digoxin) (see section “Interaction with other drugs and other types of drug interactions”). In a substudy using 24-hour Holter ECG monitoring, more patients in the acute phase of ACS had ventricular pauses in the ticagrelor group compared with clopidogrel? 3 seconds. An increase in the number of ventricular pauses recorded using 24-hour Holter monitoring while taking ticagrelor was observed more often in patients with chronic heart failure compared to the general population in the acute phase of ACS, but not in the first month of therapy and not compared with clopidogrel. Pauses in these patients were not accompanied by subsequent undesirable clinical consequences (syncope and pacemaker installation). Dyspnea Dyspnea has been reported in patients taking Brilinta®. Shortness of breath when using Brilinta® is usually mild or moderate in intensity and often goes away as drug therapy is continued. Patients with bronchial asthma/COPD may have an increased absolute risk of shortness of breath while taking Brilinta® (see section "Side effects"). In patients with asthma/COPD, ticagrelor should be used with caution. The mechanism of shortness of breath while taking ticagrelor is not clear. If the patient develops a new episode of shortness of breath, shortness of breath persists or worsens while using Brilinta®, then a full examination should be carried out, and in case of intolerance, the drug should be discontinued. Increased creatinine concentration During therapy with Brilinta®, the creatinine concentration may increase (see section “Side effects”). The mechanism of this effect is not known. Renal function should be assessed one month after starting the drug and thereafter in accordance with routine clinical practice, paying particular attention to patients aged 75 years and older, patients with moderate or severe renal impairment and those receiving angiotensin receptor antagonist therapy. Increased concentration of uric acid During therapy with Brilinta®, the concentration of uric acid may increase (see section “Side effects”). Caution should be exercised in patients with a history of hyperuricemia or gouty arthritis. As a preventive measure, the use of ticagrelor should be avoided in patients with hyperuricemic nephropathy. Others Based on the association observed in the PLATO study between the maintenance dose of ASA and the effectiveness of ticagrelor compared with clopidogrel, the combined use of a high maintenance dose of ASA (more than 300 mg) and Brilinta® is not recommended (see sections "Pharmacological properties", "Precautions" ). Concomitant use of Brilinta® with strong CYP3A4 inhibitors (for example, ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir) is contraindicated (see section "Contraindications"), as it may lead to a significant increase in the exposure of Brilinta® (see section "Interactions") with other drugs and other types of drug interactions "). Concomitant use of Brilinta® with strong CYP3A4 inducers (for example, rifampicin, phenytoin, carbamazepine and phenobarbital) is not recommended, as their combined use may reduce the exposure and effectiveness of ticagrelor (see section "Interaction with other drugs and other types of drug interactions" ). Co-administration of Brilinta® with CYP3A4 substrates with a narrow therapeutic index (for example, cisapride and ergot alkaloids) is not recommended as ticagrelor may increase the exposure of these drugs. The combined use of Brilinta® with simvastatin or lovastatin at a dose of more than 40 mg is not recommended (see section “Interaction with other drugs and other types of drug interactions”). When using digoxin and Brilinta® together, careful clinical and laboratory monitoring (heart rate, and, if clinically indicated, also ECG and digoxin concentration in the blood) is recommended. There are no data on co-administration of ticagrelor with potent P-glycoprotein inhibitors (e.g. verapamil and quinidine), which may increase ticagrelor exposure. If their combined use cannot be avoided, it should be used with caution (see sections “With caution”, “Interaction with other drugs and other types of drug interactions”). Discontinuation of therapy Early discontinuation of any antiplatelet therapy, including Brilinta®, may increase the risk of cardiovascular death or myocardial infarction as a result of the underlying disease. Premature discontinuation of the drug should be avoided. Effect of the drug on the ability to drive vehicles and operate machinery: No studies have been conducted on the effect of Brilinta® on the ability to drive vehicles and operate machinery. Brilinta® does not affect or only slightly affects the ability to drive vehicles and operate machinery. Dizziness and confusion have been reported during treatment for acute coronary syndrome. In case of development of these phenomena, patients should be careful when driving a car and other mechanisms.
Features of the rehabilitation period and recovery after stenting
The duration of cardiac recovery after cardiac stent placement is influenced by many factors. The basic category includes strict adherence to medical recommendations:
- Do not stop therapy on your own without consulting your doctor. Treatment at the postoperative stage always involves the use of two antithrombotic drugs (the main one is Aspirin, the additional one is Brilinta or Clopidogrel, Prasugrel, Effient). Your doctor decides which one to take.
- Pay attention to adequate physical activity. Light walking becomes possible already 2-3 days after discharge (10-15 minutes once a day at first, and then, gradually increasing the duration of the walk by 5 minutes, switch to twice 30-minute walks).
- Rest and sleep properly. If you have problems falling asleep, it is important to tell your doctor so that he can prescribe sedatives or sleeping pills.
- Avoid taking hot baths and showers. Heat helps dilate blood vessels and reduce blood pressure.
- Refrain from driving a car for the first 3-4 months. And if a stent is installed due to an exacerbation of coronary syndrome, the threat of a heart attack or during one, working as a driver will become impossible (due to increased stress).
- Follow a diet. An important condition for recovery is that the diet consists of fortified foods, rich in minerals and dietary fiber. Why do the menu include greens, vegetables, whole grains, legumes, fish, low-fat dairy products, chicken, turkey. While fatty, salty foods and sugary drinks should be excluded.
- Stop smoking. Tobacco leads to narrowing of arteries and damage to the endothelium of blood vessels, which increases the risk of developing embolism.
Beginning sexual activity earlier than 3 weeks after surgery is dangerous, since sex is comparable to average physical activity (similar to climbing the 2nd floor). If pain in the heart and shortness of breath occur during intimacy, be sure to consult a cardiologist. If erectile dysfunction develops, you should not raise the question of how much Brilinta to drink - therapy must definitely continue, otherwise there is a high risk of life-threatening.
BRILINTA
Side effects
Summary of Safety Profile The
safety profile of Brilinta® was assessed in two phase 3 studies (PLATO and PEGASUS), which included more than 39,000 patients (see section "Pharmacological properties"). The following are the adverse reactions observed in these clinical studies.
In the PLATO study, patients receiving Brilinta® were more likely to discontinue therapy due to adverse events than patients receiving clopidogrel (7.4% versus 5.4%).
In the PEGASUS study, the rate of treatment discontinuation due to adverse events was higher with Brilinta® than with ASA monotherapy (16.1% in the ticagrelor 60 mg + ASA group compared with 8.5% in the ASA monotherapy group). The most commonly reported adverse reactions in patients taking ticagrelor were bleeding and shortness of breath (see section "Special Instructions").
List of adverse reactions in table form
Adverse reactions from clinical studies of Brilinta® are presented by organ system class and frequency of occurrence and are listed in descending order of severity. The frequency of adverse reactions is determined using the following symbols: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1 /10000, <1/1000), very rare (<1/10000), unspecified frequency (cannot be estimated from the data obtained).
Table 1. Adverse reactions by incidence and organ system class observed in the phase 3 clinical studies PLATO and PEGASUS
| Class of organ systems | Often | Often | Infrequently |
| Benign, malignant and unspecified neoplasms (including cysts and polyps) | Bleeding from a tumora | ||
| Blood and lymphatic system disorders | Bleeding associated with blood diseasesb | ||
| Immune system disorders | Hypersensitivity reactions, including angioedema | ||
| Metabolic and nutritional disorders | Hyperuricemiad | Gout/ gouty arthritis | |
| Mental disorders | Confusion | ||
| Nervous system disorders | Dizziness, fainting, headache | Intracranial hemorrhage | |
| Visual disorders | Bleeding in the eye | ||
| Hearing and labyrinth disorders | Vertigo | Ear bleeding | |
| Vascular disorders | Arterial hypotension | ||
| Respiratory, thoracic and mediastinal disorders | Dyspnea | Bleeding from the respiratory systemf | |
| Gastrointestinal disorders | Gastrointestinal bleedingg, diarrhea, nausea, dyspepsia, constipation | Retroperitoneal bleeding | |
| Skin and subcutaneous tissue disorders | Subcutaneous or skin bleedingh, skin itching, rash | ||
| Musculoskeletal and connective tissue disorders | Muscle bleeding | ||
| Renal and urinary tract disorders | Bleeding from the urinary tractj | ||
| Genital and breast disorders | Bleeding from the genitals | ||
| Laboratory and instrumental data | Increased blood creatinine concentrationd | ||
| Injuries, intoxications and complications of manipulations | Bleeding after manipulation, traumatic bleeding |
a For example, bleeding from a bladder tumor, from a stomach tumor, from a colon tumor.
b for example, increased tendency to bruise, spontaneous hematoma, bleeding diathesis.
observed during post-marketing use.
d the frequency of laboratory abnormalities (increase in uric acid concentration above the upper limit of normal from a baseline value that was within the normal range or less than the lower limit of normal. Increase in creatinine concentration > 50% of the baseline value) is reported, rather than the frequency of reports of adverse events.
e.g., conjunctival, retinal, intraocular hemorrhage.
f for example, epistaxis (nosebleeds), hemoptysis.
g e.g. gingival bleeding, rectal bleeding, bleeding from stomach ulcers.
h for example, ecchymosis, cutaneous hemorrhage, petechiae.
i for example, hemarthrosis, hemorrhage into the muscle,
jfor example, hematuria, hemorrhagic cystitis.
k for example, vaginal bleeding, hematospermia, postmenopausal bleeding.
l for example, bruise, traumatic hematoma, traumatic bleeding.
Description of some adverse reactions
Bleeding
The following definitions of bleeding were used in the PLATO and PEGASUS studies:
— Major lethal/life-threatening bleeding according to PLATO definition:
lethal, or any intracranial hemorrhage, or bleeding into the pericardial cavity with cardiac tamponade; or with hypovolemic shock or severe hypotension requiring the use of vasoconstrictors/inotropes or surgery, or clinically overt bleeding accompanied by a decrease in hemoglobin concentration of more than 50 g/L, or a transfusion of 4 or more units of red blood cells.
— Major other bleeding according to PLATO definition:
causing significant disability of the patient, or clinically obvious bleeding, accompanied by a decrease in hemoglobin concentration by 30-50 g/l, or transfusion of 2-3 units of red blood cells.
— Minor bleeding according to PLATO definition:
requires medical intervention to stop or treat bleeding.
- Major bleeding according to TIMI definition:
lethal, or any intracranial hemorrhage, or clinically overt bleeding associated with a decrease in hemoglobin concentration of 50 g/L or more, or, if hemoglobin data are not available, a decrease in hematocrit of 15%.
- Major other bleeding according to TIMI definition:
non-fatal, non-intracranial major bleeding as defined by TIMI.
— Minor bleeding according to TIMI definition:
clinically obvious bleeding, accompanied by a decrease in hemoglobin concentration by 30-50 g/l.
— Bleeding requiring medical intervention, as defined by TIMI
: Requires medical intervention or results in hospitalization or emergency evaluation.
— Lethal bleeding
: Leads to the death of the patient within 7 days.
Data on bleeding events in the PLATO study (Kaplan-Meier estimate (%) at 12 months)
Brilinta® and clopidogrel did not differ in the incidence of major bleeding overall according to PLATO criteria (11.6% and 11.2%, respectively), or fatal/life-threatening bleeding according to PLATO criteria (5.8% in both groups). However, the incidence of combined major and minor bleeding according to PLATO criteria was higher in the ticagrelor group (16.1%) compared with clopidogrel (14.6%, p = 0.0084). There were several cases of fatal bleeding: 20 (0.2% of patients) in the ticagrelor group and 23 (0.3% of patients) in the clopidogrel group.
Age, sex, weight, ethnicity, geographic region, comorbidities, concomitant therapies, and medical history, including previous stroke and transient ischemic attack, did not influence the incidence of overall and nonprocedure-related major bleeding according to PLATO criteria. No groups were identified with an increased risk of bleeding.
Bleeding associated with CABG:
In the PLATO trial, 42% of 1584 patients (12% of the cohort) undergoing CABG experienced major lethal/life-threatening bleeding, with no difference in either treatment group. Fatal bleeding associated with CABG surgery occurred in 6 patients in each treatment group (see section "Special Instructions").
Non-CABG bleeding and non-procedure-related bleeding:
Brilinta® and clopidogrel did not differ in the incidence of major fatal/life-threatening bleeding not associated with CABG according to PLATO criteria, but ticagrelor was more likely to develop major bleeding overall according to PLATO criteria (4.5% versus 3.8%; p=0.0264). When removing procedure-related bleeding events, there were more bleeding events in the ticagrelor group (3.1%) than in the clopidogrel group (2.3%; P = 0.0058). Discontinuation due to nonprocedure-related bleeding was more common with ticagrelor (2.9%) compared with clopidogrel (1.2%, p < 0.001).
Intracranial hemorrhage:
There were more non-procedure-related intracranial hemorrhages in the ticagrelor group (n=27 hemorrhages in 26 patients, 0.3%) than in the clopidogrel group (n=14 hemorrhages, 0.2%), of which 11 hemorrhages occurred on ticagrelor and 1 on clopidogrel were fatal. However, there were no significant differences in the total number of fatal bleeding events. The percentage of intracranial hemorrhage was low in both treatment groups, given the significant comorbidities and risk factors for cardiovascular complications in the study population.
Data on bleeding events in the PEGASUS study (Kaplan-Meier estimate (%) at 36 months)
In the PEGASUS study, major bleeding as determined by TIMI occurred more frequently with Brilinta® 60 mg twice daily (2.3%) than with ASA monotherapy (1.1%). There was no increase in the risk of fatal bleeding, but only a slight increase in the incidence of intracranial hemorrhage (0.6%) compared with ASA monotherapy (0.5%). Several cases of fatal bleeding were noted: 11 (0.3%) in the Brilinta® 60 mg group and 12 (0.3%) in the ASA monotherapy group. The increased risk of TIMI major bleeding with Brilinta 60 mg was primarily due to a higher incidence of other TIMI major bleeding due to gastrointestinal events.
With the use of Brilinta® 60 mg, an increase in the frequency of major or minor bleedings according to the TIMI definition was noted (3.4% when using the drug Brilinta® 60 mg compared to 1.4% with ASA monotherapy), major bleedings according to the PLATO definition (3. 5% versus 1.4%) and major or minor bleeding as defined by PLATO (15.2% versus 6.2%). Treatment discontinuation due to bleeding was more common with Brilinta 60 mg than with ASA monotherapy (6.2% and 1.5%, respectively). Most of these bleeds were less severe (classified as bleeds requiring medical attention, as defined by TIMI), such as epistaxis, bruising, and hematomas.
The profile of TIMI major bleeding, TIMI major or minor bleeding, and PLATO major bleeding for Brilinta 60 mg was comparable across several prespecified subgroups (eg, age, sex, weight, race, geographic region , concomitant diseases, concomitant medications and medical history).
Intracranial hemorrhage:
Spontaneous intracranial hemorrhage was noted with a similar frequency when using Brilinta® 60 mg and ASA monotherapy (n = 13 hemorrhages, 0.2% in both treatment groups). The incidence of intracranial hemorrhage due to trauma and procedure was slightly higher with Brilinta 60 mg (n=15 hemorrhages, 0.2%) compared with ASA monotherapy (n=10 hemorrhages, 0.1%). There were 6 fatal intracranial hemorrhages when taking Brilinta® 60 mg and 5 when taking ASA monotherapy. The incidence of intracranial hemorrhage was low in both treatment groups, given the significant comorbidities and cardiovascular risk factors in the study population.
Dyspnea
In the PLATO study, adverse events of dyspnea occurred in 13.8% of patients receiving ticagrelor 90 mg twice daily and in 7.8% of patients receiving clopidogrel 75 mg once daily. Most symptoms of dyspnea were mild to moderate in intensity and often resolved without discontinuation of therapy. Typically, shortness of breath developed at the beginning of therapy and in 87% of patients it was a single episode. Dyspnea as a serious adverse event was reported in 0.7% of patients receiving ticagrelor and in 0.4% of patients receiving clopidogrel.
Patients who reported developing dyspnea were older and often initially had dyspnea, congestive heart failure, COPD, or asthma. Data from the PLATO trial do not indicate that the higher incidence of dyspnea with Brilinta is associated with the development of new or worsening heart or lung disease. Brilinta® does not affect respiratory function parameters (see section “Special instructions”).
In the PEGASUS study, shortness of breath was observed in 14.2% of patients taking Brilinta 60 mg twice daily and in 5.5% of patients taking ASA monotherapy. As in the PLATO study, most cases of shortness of breath were mild to moderate in intensity (see section "Special Instructions").
How much should you take Brilinta after stenting?
Only an experienced specialist can conduct regular monitoring of the patient’s condition, and, if necessary, take timely measures to eliminate bleeding. This is especially important for patients with coronary heart disease, who often experience bleeding during treatment with this medicine.
Only a doctor, taking into account the specific clinical picture, determines how much Brilinta to drink. According to the manufacturer's instructions, this medication must be taken for at least a year. After this period, the possibility of excluding the antithrombotic from drug therapy is considered, taking into account laboratory tests.
