Dual antiplatelet therapy

Dual antiplatelet therapy consists of the concurrent administration of aspirin and a P2Y12 inhibitor.

Dual antiplatelet therapy is the mainstay in the secondary prevention of cardiovascular events in patients with recent history of myocardial infarction or recent percutaneous coronary intervention with stent placement.

Patients who are most vulnerable to the risks of dual antiplatelet therapy those or add heightened bleeding risk: patients 75 years or older, patient with a clinical indication for oral anticoagulants, stroke,  transient ischemic attack, systemic conditions associated with increase bleeding, long-term treatment with corticosteroids and nonsteroidal anti-inflammatory drugs, previous bleeding event, or anemia or receipt of blood transfusion.

Attempts to reduce stroke risk from the use of dual antiplatelet agents has been disappointing, showing no benefit but an increased risk of hemorrhage.

Among patients with mild ischemic stroke or high risk TIA of presumed atherosclerotic cause, combined clopidogrel and aspirin therapy initiated within 72 hours after stroke onset lead to a lower risk of new stroke at 90 days than aspirin therapy alone, but was associated with a low but higher risk of moderate to severe bleeding. (INSPIRES investigators).

Requires prolonged use of the dual antiplatelet agents post PCI procedure for at least one month after bare metal stent implantation and 12 months after drug eluting stent implantation.

Randomized trials establish the superiority of drug eluting stent over bare metal stents in patients at high risk of bleeding receiving one month of dual antiplatelet therapy after undergoing PCI.

One month of dual antiplatelet therapy in drug eluting stent was not inferior to the continuation of therapy for at least two additional months with regard to the recurrence or net adverse clinical events and major adverse cardiac or cerebral events, and abbreviated therapy resulted in a lower incidence of major or clinically relevant non-major bleeding (Valgimigli M).

The three anti-platelet agents include clopidogrel, Prasugrel, and Ticagrelor are currently used in combination with aspirin,

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is recommended for one year after myocardial infarction to reduce the risk of major adverse cardiovascular events, with practice guidelines supporting ticagrelor,or prasugrel over clopidogrel because of improved clinical outcomes.

Clopidogrel is the most commonly use of these agents.

The use of clopidogrel plus aspirin is a major oral anti-thrombotic strategy in patients with cardiovascular disease.

Antiplatelet therapy is the standard of care for secondary prevention of ischemic stroke.

Guidelines recommend the use of aspirin, clopidogrel , or aspirin in combination with extended release dipyridamole as the antiplatelet treatment of choice.

Estimated number of emergency department visits for hemorrhage related to complications of dual antiplatelet therapy is 7654 cases annually and accounts for just more than 10% that from warfarin 60,575 annually. oral anti-thrombotic strategy in patients with cardiovascular disease (Shehab N et al).

The combination of aspirin and dipyridine compared to aspirin alone in patients with cerebrovascular disease is superior in preventing new strokes and other cardiovascular events without an increase in bleeding episodes.

The use of of clopidogrel showed no difference in the rate of recurrent stroke when compared to aspirin or the combination of aspirin and dipyridamole.

Estimated that for every 815 outpatient visits of patients on dual antiplatelet therapy, one patient presents to the emergency department for related bleeding or evaluation for such bleeding, compared for every 274 outpatient visits at which warfarin was prescribed ( Shehab N et al).

60% of emergency department visits for dual antiplatelet therapy with aspirin plus clopidogrel related acute hemorrhages involved epistaxis, skin or other minor bleeding (Shehab N et al).

Dual antiplatelet therapy is used for the prevention of ischemic complications after implantation of drug eluding stents.

The optimal duration of the dual antiplatelet therapy after stent implantation remains unclear.

The STOPDAPT-2 randomized trial revealed among patients undergoing PCI, one month of dual antiplatelet therapy followed by clopidogrel monotherapy, compared with 12 months of dual antiplatelet therapy with aspirin and Clopidogrel resulted in significant lower rate of cardiovascular and bleeding events suggesting a shorter duration of dual antiplatelet therapy may provide benefit.

In the SMART-CHORICE randomized clinical trial among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after three months of DAPT compared with prolonged DAPT resulted in non-inferior rates of major adverse cardiac and cerebrovascular events.

With zotarolimus stents patients with stable coronary artery disease or low risk acute coronary syndrome treated with three months of dual antiplatelet therapy was not inferior to 12 months of therapy, without significantly increasing the risk of stent thrombosis (OPTIMIZE Triall Investigators).

The American College of cardiology recommends 12 months of dual antiplatelet therapy after an acute coronary syndrome, irrespective of the revascularization strategy.

In a non-acute coronary syndrome setting on the American College of Cardiology recommends dual antlatelet therapy for 12 months if patient is not as high risk for bleeding, has chronic kidney disease, greater than 75 years, oron concomitant anti-coagulant drug therapy.

In patients with acute coronary syndrome short duration dual antiplatelet therapy is associated with higher rates of stent thrombosis, myocardial infarction, target vessel revascularization, without a reduction in bleeding risk compared with long duration dual antiplatelet therapy.

A Cochrane review on the association of aspirin with clopidogrel with the outcomes of mortality, cardiovascular events, and major bleeding versus aspirin alone among patients at high risk for or at high risk with cardiovascular disease: results were dual anti-platelet therapy was not associated with lower cardiovascular mortality compared with aspirin alone, or all-cause mortality (Donadini MP).

In the Cochrane review aspirin plus clopidogrel was associated with reduced risk of fatal or non-fatal myocardial infarction compared with aspirin alone and with a reduced risk with fatal or non-fatal ischemic stroke.

Among patients with minor non-disabling, acute ischemic stroke presenting within 4 1/2 hours of symptom onset, dual antiplatelet therapy was not inferior to intravenous Alteplase with regard to excellent functional outcome at 90 days (ARAMIS investigators).

In the Cochrane review The above combination was associated with a higher risk of major bleeding compared with the aspirin alone.

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