Clopidogrel Bisulfate and Renal dysfunction

• Generic Name: clopidogrel
• Dosage Forms: n.a.
• Other Brand Names: Plavix

Reduction of the risk of cardiovascular or cerebrovascular events (new MI, new ischemic stroke, and vascular death) in patients with a history of recent MI, recent ischemic stroke, or established peripheral arterial disease.

The American College of Chest Physicians (ACCP) recommends long-term antiplatelet therapy with either aspirin or clopidogrel in patients with established CAD. Because of cost considerations, clopidogrel generally recommended as an alternative to aspirin in those with aspirin intolerance or contraindications (e.g., allergy).

ACCP, the American Stroke Association (ASA), and AHA consider clopidogrel an acceptable antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke or TIAs; other options include aspirin monotherapy, cilostazol, or the combination of aspirin and extended-release dipyridamole.

Oral anticoagulation (e.g., warfarin, dabigatran) rather than antiplatelet therapy is recommended in patients with a history of ischemic stroke or TIA and concurrent atrial fibrillation; however, in patients who cannot take or choose not to take oral anticoagulants (e.g., those with difficulty maintaining stable INRs, compliance issues, dietary restrictions, cost limitations), dual antiplatelet therapy with clopidogrel and aspirin is recommended.

Recommended by ACCP and other experts as an acceptable antiplatelet therapy for secondary prevention of cardiovascular events in patients with symptomatic peripheral arterial disease, including those with intermittent claudication and those undergoing revascularization procedures (peripheral artery percutaneous transluminal angioplasty or peripheral artery bypass graft surgery, carotid endarterectomy).

Recommended by ACCP as an option for long-term antiplatelet therapy in patients with symptomatic carotid stenosis, including in patients who are intolerant of aspirin and those who have undergone recent carotid endarterectomy.

Used in combination with aspirin for reduction of the risk of cardiovascular or cerebrovascular events in patients with NSTE ACS, including unstable angina and non-ST-segment-elevation MI (NSTEMI). Used in patients who are managed medically or with coronary revascularization (e.g., PCI with or without coronary artery stenting, CABG).

Dual-drug antiplatelet therapy with a P2Y12-receptor antagonist and aspirin is considered part of the current standard of care in patients with NSTE ACS.

Experts state that aspirin should be administered as soon as possible after presentation (and continued indefinitely) in all patients with NSTE ACS unless contraindicated; in addition, a P2Y12-receptor antagonist should be administered for up to 12 months.

Ticagrelor or clopidogrel generally recommended as the P2Y12-receptor antagonist of choice in patients treated medically without stent placement; ticagrelor, clopidogrel, or prasugrel is recommended in patients undergoing PCI with stent placement (bare-metal or drug-eluting).

When selecting an appropriate antiplatelet regimen, consider individual patient (e.g., ischemic and bleeding risk) and drug-related (e.g., adverse effects, drug interaction potential) factors.

Efficacy of pretreatment with clopidogrel prior to diagnostic cardiac catheterization is controversial; balance potential benefit of pretreatment against increased risk of bleeding should emergency CABG be needed.

Temporarily discontinue therapy ≥5 days prior to CABG.

Used in combination with aspirin for reduction of the rate of ischemic cardiovascular and cerebrovascular events in patients with STEMI.

In patients in whom CABG is planned, withhold clopidogrel for ≥5 days prior to surgery.

In patients with STEMI in whom PCI is planned, experts recommend a loading dose of a P2Y12-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) before or at the time of PCI in conjunction with aspirin therapy. Clopidogrel also has been used in patients with STEMI who are receiving delayed PCI after thrombolytic therapy.

Continue therapy for ≥12 months after stent implantation (bare-metal or drug-eluting), unless risk of bleeding outweighs anticipated net benefit; continue aspirin therapy indefinitely. (See Risks of Premature Discontinuance of Therapy under Cautions.)

The addition of warfarin to antiplatelet therapy is recommended in STEMI patients who have indications for anticoagulation (e.g., atrial fibrillation, left ventricular dysfunction, cerebral emboli, extensive wall-motion abnormality, mechanical heart valves).

Triple antithrombotic therapy with clopidogrel, low-dose aspirin, and warfarin (target INR 2–3) is suggested by ACCP in patients with anterior MI and left ventricular thrombus (or at high risk for such thrombi) undergoing stent implantation; recommended duration of triple antithrombotic therapy is dependent on whether patient has a bare-metal or drug-eluting stent.

Suggested by the American Diabetes Association (ADA) as alternative to aspirin for primary prevention of MI in aspirin-allergic patients with type 1 or type 2 diabetes mellitus who are at high risk for cardiovascular events (i.e., family history of CHD, smoking, hypertension, obesity, albuminuria, elevated blood cholesterol or triglyceride concentrations).

Has been used in combination with aspirin (dual-drug therapy) to prevent stent thrombosis following implantation of coronary artery stents.

Current expert guidelines recommend such dual-drug therapy for ≥12 months in patients with any type of coronary artery stent (bare-metal or drug-eluting).

Some evidence suggests benefits of an even longer duration of dual-drug antiplatelet therapy (e.g., at least 30 months), but such prolonged therapy has been associated with an increased risk of bleeding.

May be used as an alternative to aspirin in patients with symptomatic chronic stable angina who cannot tolerate aspirin. In certain high-risk patients, combination therapy with aspirin and clopidogrel may be beneficial.

Has been used in combination with aspirin as an alternative to warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation.

In patients with atrial fibrillation at increased risk of stroke who cannot or choose not to take oral anticoagulants for reasons other than concerns about major bleeding (e.g., those with difficulty maintaining stable INRs, compliance issues, dietary restrictions, cost limitations), combination therapy with clopidogrel and aspirin rather than aspirin alone is recommended.

In patients with atrial fibrillation and mitral stenosis who cannot or choose not to take warfarin therapy for reasons other than concerns about major bleeding, ACCP recommends combination therapy with clopidogrel and aspirin rather than aspirin alone.

Antithrombotic therapy of atrial flutter generally managed in same manner as atrial fibrillation.