Intolerance and low response to commonly used antiplatelet drugs?

Antiplatelet drug intolerance refers to the situation that patients cannot insist on taking one or more antiplatelet drugs for a long time due to possible or existing adverse reactions of antiplatelet drugs

Treatment strategies for antiplatelet drug-intolerant populations

Common types of antiplatelet drug intolerance include gastrointestinal injury and hemorrhage, intracranial hemorrhage, hemorrhage in other parts, and gout/hyperuricemia.

Peptic ulcer and bleeding population

If the symptoms of gastrointestinal injury such as acid regurgitation, nausea and abdominal distension occur due to taking aspirin, aspirin can be discontinued and acid suppressants or H2 receptor blockers combined with gastric mucosal protective agents can be given, or other antiplatelet drugs can be used instead

For patients with gastrointestinal bleeding during DAPT, the primary disease should be actively treated, and the risk of bleeding and ischemia should be weighed before deciding whether to discontinue antiplatelet therapy and when to resume antiplatelet therapy: ①Mild bleeding does not need to stop DAPT; ②If If there is significant bleeding (hemoglobin drops by 30 g/L or requires hospitalization, but does not cause hemodynamic disturbance), aspirin may be discontinued first, and antiplatelet drugs may be discontinued if life-threatening active bleeding occurs; ③ After the condition is stable, resume antiplatelet therapy as soon as possible under the condition of ensuring safety, usually resume clopidogrel after 3-5 days, resume aspirin after 5-7 days or change to indobufen/cilostazol; ④If taking For patients with gastrointestinal bleeding on ticagrelor, discontinue ticagrelor, and consider switching to clopidogrel if the bleeding is mild or moderate; for patients with severe bleeding that requires discontinuation of P2Y12 receptor inhibitor therapy, switch to clopidogrel after the bleeding stops Use clopidogrel in combination with indobufen or cilostazol

intracerebral hemorrhage

Patients with spontaneous cerebral hemorrhage during antiplatelet therapy should stop the drug immediately.

For patients with ischemic stroke with hemorrhagic transformation, antithrombotic therapy may be considered as appropriate 10 days to several weeks after symptomatic hemorrhagic transformation has stabilized

For patients with cerebral hemorrhage over the age of 75, it is recommended to restart antithrombotic therapy after evaluating the hemorrhage by imaging

People with bleeding from other organs

Minor bleeding: Any bleeding that does not require drug intervention or further evaluation, such as skin abrasions, petechiae, self-healing epistaxis, and minor conjunctival hemorrhage, continuous antiplatelet therapy is recommended, and switching to low-potency P2Y12 receptors may be considered as appropriate inhibitors, indobufen, or cilostazol

Minor bleeding: Any bleeding requiring medical attention but not requiring hospitalization, suggest continued antiplatelet therapy, consider shortening the course of DAPT or switching to a low-potency P2Y12 receptor inhibitor, indobufen, or cilostazol; identify bleeding-related Complications (eg, kidney stones, hemorrhoids, tumors) and possible treatment

Moderate bleeding: Any bleeding leading to hemoglobin loss >30 g/L and/or requiring hospitalization, but hemodynamically stable and the disease will not progress rapidly, try to use single-agent antiplatelet therapy (SAPT), preferably P2Y12 DAPT can be resumed as soon as possible according to the situation after it is considered safe, and the principle of drug selection is the same as above

Major bleeding: Any bleeding that results in a loss of hemoglobin >50 g/L and requires hospitalization, but is hemodynamically stable and does not progress rapidly

Life-threatening bleeding: Any serious active bleeding that threatens the patient's life, discontinue all antithrombotic drugs, and once the bleeding stops, reassess the need for DAPT or SAPT, SAPT preferably P2Y12 receptor inhibitor, indobufen, or cilostazol

People with gout/high uric acid

If gout occurs during DAPT after stenting, the ischemia and gout hazards should be weighed, and combined anti-gout drugs can be considered, or aspirin can be replaced by indobufen or cilostazol

For patients with stable coronary heart disease, ischemic stroke, or peripheral arterial disease who do not require DAPT treatment, if combined with hyperuricemia or gout, antiplatelet drugs that have little effect on purine metabolism are preferred, such as clopidogrel and indobufen or cilostazol

elderly people

Aspirin or clopidogrel can be the first choice, and indobufen or cilostazol can be used in patients with high bleeding risk

people with high blood pressure

For hypertensive patients with non-acute stroke or transient ischemic attack, antiplatelet drugs should be used as appropriate after the blood pressure reaches the target value.

People with renal insufficiency

Aspirin, indobufen or cilostazol are recommended for patients with mild to moderate renal insufficiency, and changes in renal function should be closely monitored during aspirin use
.

Severe renal insufficiency and dialysis patients: Avoid aspirin and ticagrelor as much as possible.
SAPT program recommends using indobufen or cilostazol
.

Therapeutic strategy for antiplatelet drug hyporesponsive population

For patients with high ischemic risk or poor prognosis, high bleeding risk or coronary heart disease with bleeding, as well as ischemic stroke or PAD, genetic testing and platelet function testing can be considered as a reference for the use of antiplatelet drugs
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In patients requiring changes in antiplatelet drugs, platelet function can be measured to guide switching to P2Y12 receptor inhibitors
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For patients at high ischemic risk who have undergone complex percutaneous coronary intervention, genetic testing should be performed prior to taking clopidogrel
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Expert advice for aspirin hyporesponsive people

Consider switching to other antiplatelet drugs, such as indobufen or clopidogrel; when aspirin is co-administered with a P2Y12 receptor inhibitor, an increase in aspirin dose is not recommended (more than 100 mg/d)
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Expert advice for clopidogrel hyporesponsive populations

For those who have no response or low response to conventional doses of clopidogrel, especially those with diabetes, it is not recommended to increase the dose of clopidogrel, and it is recommended to switch to other antiplatelet drugs, such as ticagrelor; if there is a high risk of bleeding Factors, or for other reasons can not accept P2Y12 receptor inhibitor therapy, can switch to aspirin, indobufen or cilostazol (non-heart failure or coronary artery stenosis patients)
.

references:

1.
Huo Yong, Wang Yongjun, Gu Yongquan, Huang Kai, Xu Anding, Zheng Yuehong, Ge Junbo.
Expert consensus on the diagnosis and treatment of people with intolerance and low response to commonly used oral antiplatelet drugs [J].
Chinese Journal of Interventional Cardiology, 2021, 29( 05): 240-249.

2.
The 2022 Tiantan Society academic report "Assessment and Management of Antiplatelet Drug Intolerance and Hyporesponsive Population" by Professor Xu Yun from the Drum Tower Hospital Affiliated to Nanjing Drum Tower University School of Medicine
.