{"id":189,"date":"2019-10-07T22:09:22","date_gmt":"2019-10-07T16:39:22","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=189"},"modified":"2019-10-07T22:09:22","modified_gmt":"2019-10-07T16:39:22","slug":"anti-platelet-drugs","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/anti-platelet-drugs\/","title":{"rendered":"Anti-platelet Drugs"},"content":{"rendered":"\n<p><strong>Anti-platelet agents<\/strong><\/p>\n\n\n\n<ul><li>interfere with platelet function and are useful in the prophylaxis of thromboembolic disorders<\/li><li>In veins, due to sluggish blood flow, a fibrinous tail is formed which traps RDCs &#8216; the red tail &#8216;. <\/li><li>In arteries, platelet mass is the main constituent of the thrombus. <\/li><li><strong>Antiplatelet drugs are, therefore, more useful in arterial thrombosis. while anticoagulants are more effective in venous thrombosis.<\/strong><\/li><\/ul>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"549\" height=\"225\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-41.png?w=549\" alt=\"\" class=\"wp-image-190\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-41.png 549w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-41-300x123.png 300w\" sizes=\"(max-width: 549px) 100vw, 549px\" \/><\/figure><\/div>\n\n\n\n<p><strong>COX inhibitor <\/strong><strong>\u00e0 Aspirin <\/strong><\/p>\n\n\n\n<ul><li>acetylates the enzyme COX I and\nTX-synthase- inactivating them irreversibly. TXA2 activates platelets to change\nshape and release mediator rich granules that promote aggregation.<\/li><li>Because platelets cannot\nsynthesize fresh enzyme (have no nuclei), TXA2 formation is suppressed at very\nlow doses and till fresh platelets are formed. Thus, aspirin-induced\nprolongation of bleeding time last for 5- 7 days<\/li><li>Maximal inhibition of platelet\nfunction occurs at 75- 150 mg aspirin per day.<\/li><li>(ACC\/AHA)* guidelines recommend\na dose of <strong>75- 162 mg\/ day for long-term\naspirin prophylaxis.<\/strong><\/li><li>higher doses (&gt; 900 mg\/day)\nmay decrease both TXA2 and PGl2 production<\/li><li>PGI2 is strong inhibitor of\nplatelet aggregation, therefore low doses used. <\/li><li>Other NSAIDs arc reversible\ninhibitors of COX, produce shor1-las1ing inhibition of platelet function-are not\nclinically useful.<\/li><\/ul>\n\n\n\n<p><strong>PDE inhibitor <\/strong><strong>\u00e0 Dipyridamole <\/strong><\/p>\n\n\n\n<ul><li>inhibits phosphodiesterase as\nwell as blocks uptake of adenosine to increase platelet cAMP which in turn\npotentiates PGI2 and interferes with aggregation<\/li><li>Dipyridamole alone has a little\nclinically significant effect. but improves the response to warfarin, along\nwith which it is used to decrease the incidence of thromboembolism in patients\nwith prosthetic heart valves.<\/li><li>Dipyridamole has also been used\nto enhance the antiplatelet action of aspirin. This combination may\nadditionally lower the risk of stroke in patients with transient ischemic\nattacks (TIAs)<\/li><\/ul>\n\n\n\n<p><strong>ADP antagonist<\/strong><\/p>\n\n\n\n<ul><li><strong>Ticlopidine <\/strong><strong>\u00e0 <\/strong>acts by blocking the P2Y 12 receptors\non the surface of platelets and inhibits ADP-induced aggregation. <\/li><li><strong>s\/e- neutropenia and thrombocytopenia<\/strong><\/li><\/ul>\n\n\n\n<ul><li><strong>Clopidogrel <\/strong><strong>\u00e0<\/strong> more potent congener of ticlopidine, the same range of therapeutic\nefficacy, but is safer and better tolerated (CLASSICS study).<\/li><li>A combination of clopidogrel and\naspirin is synergistic in preventing ischemic episodes \u00e0 <strong>&#8216; dual antiplatelet therapy&#8217; (DAPT)<\/strong> is\nalso utilized for checking restenosis of stented coronaries. \u00e0 <strong>but increase bleeding risk<\/strong><\/li><li>Omeprazole, an inhibitor of\nCYP2C 19, reduces metabolic activation of clopidogrel and its antiplatelet\naction. <\/li><li>The action lasts for 5 days due\nto the irreversible blockade of platelet P2Y 12 receptor.<\/li><li>The most important adverse\neffect is bleeding<\/li><\/ul>\n\n\n\n<ul><li><strong>Prasugrel<\/strong> \u00e0 newer<strong> most potent <\/strong>and faster-acting P2Y12\nreceptor blocker. <\/li><li>interference by omeprazole\ntreatment has not been prominent.<\/li><li>Because of <strong>rapid action,<\/strong> prasugrel is <strong>particularly\nsuitable for use in STEMI.<\/strong> <\/li><li><strong>Preferred thienopyridine in ACS<\/strong> to cover\nangioplasty with or without stent placement.<\/li><li>Superior clinical outcomes and reduction\nin Stent thrombosis have been obtained with prasugrel.<\/li><\/ul>\n\n\n\n<ul><li><strong>Ticagrelor <\/strong>\u00e0 <strong>latest P2Y12 receptor\ninhibitor &#8211;ORAL<\/strong><\/li><li>acts directly without needing\nmetabolic activation.<\/li><li>Unlike clopidogrel and\nprasugrel, the action of ticagrelor is reversible. Thus, it has a faster onset\nand quicker offset of action; the biological t\u00bd is 12 hours, and it needs twice-daily\nadministration<\/li><li><strong>The PLATO trial<\/strong> compared ticagrelor with\nclopidogrel in patients with ACS and reported lower cardiovascular mortality as\nwell as all-cause mortality with ticagrelor. <\/li><li>The <strong>risk of intracranial bleeding was higher with ticagrelor<\/strong>, <strong>but that of all major bleeds was similar<\/strong><\/li><li>The European guidelines now\nrecommend that all patients at high risk of ACS be given prophylactic ticagrelor<\/li><\/ul>\n\n\n\n<ul><li><strong>Cangrelor <\/strong><strong>\u00e0 intravenous<\/strong><\/li><\/ul>\n\n\n\n<ul><li><strong>Vorapaxar, Atopaxar <\/strong><strong>\u00e0 PAR antagonist<\/strong><\/li><li>Orally active inhibitor of\nthrombin receptors on platelet called protease-activated receptor 1 <\/li><li>Approved as an antiplatelet\ndrug in patients with a history of MI or peripheral artery disease. <\/li><\/ul>\n\n\n\n<p><strong>Glycoprotein (GP) IIb\/ Illa receptor antagonists<\/strong><\/p>\n\n\n\n<ul><li>GP IIb\/ IIIa is an adhesive\nreceptor (integrin) on platelet surface for fibrinogen and vWF through which\nagonists like collagen, thrombin, TXA2, ADP, etc. finally induce platelet\naggregation. <\/li><li>Thus, GP IIb\/ IIIa antagonists <strong>block aggregation induced by all platelet\nagonists.<\/strong><\/li><li>used only in patients with ACS\nand to cover PCT or coronary artery bypass grafting (CABG).<\/li><\/ul>\n\n\n\n<ul><li><strong>Abciximab <\/strong>\u00e0a chimeric monoclonal antibody against GP IIb\/ IIIa protein<\/li><li>S\/e \u00e0\nhemorrhage, thrombocytopenia<\/li><li>It is expensive. but is being\nused in unstable angina and as an adjuvant to coronary thrombolysis\/ PCI with\nstent placement<\/li><li><strong>Eptifibatide<\/strong><\/li><li><strong>Tirofiban<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Uses of antiplatelet drugs<\/strong><\/p>\n\n\n\n<ul><li>To prevent intravascular\nthrombosis and embolization, with minimal risk of hemorrhage. <\/li><li>Those with CAD or risk factors\nfor stroke are generally given a single drug (aspirin\/ clopidogrel). <\/li><li>For indications like ACS, maintenance\nof vascular recanalization, stent placement, vessel grafting, etc. potent inhibition\nrequired \u00e0 (dual antiplatelet therapy).<\/li><\/ul>\n\n\n\n<ol><li><strong>Coronary artery disease<\/strong> <ol><li>it is recommended that aspirin\n75- 150 mg\/day be given to all&nbsp; individuals\nwith evidence of coronary artery disease<\/li><\/ol><ol><li>It reduces the incidence of\nfatal as well as nonfatal MI but increases the risk of a cerebral hemorrhage. <\/li><\/ol><ol><li>Continued aspirin\/ clopidogrel\nprophylaxis in post-Ml patients clearly prevents reinfarction and reduces\nmortality.<\/li><\/ol><\/li><\/ol>\n\n\n\n<ul><li><strong>Acute coronary syndromes (ACS)<\/strong> <ul><li>range of acute cardiac ischemia\nstates from unstable angina (UA) to non-ST elevation myocardial infarction\n(NSTEMI) to STEMI<\/li><\/ul><ul><li>Soluble aspirin (325 mg oral)\nand an LMW heparin (s.c.) are given at presentation to all patients with ACS.<\/li><\/ul><ul><li><strong>Unstable angina<\/strong> \u00e0 Aspirin\nreduces the risk of progression to MI and sudden death. <\/li><\/ul><ul><li>Clopidogrel is generally\ncombined with aspirin or may be used as an alternative if aspirin cannot be\ngiven. <\/li><\/ul><ul><li>For maximum protection, the\nantiplatelet drugs are supplemented with heparin followed by warfarin.<\/li><\/ul><ul><li><strong>NSTEMI<\/strong>\u00e0 Patients of NSTEMI who are managed without PCI\/thrombolysis are\ngenerally put on a combination of aspirin + clopidogrel, which is continued up to\none year.<\/li><\/ul><ul><li><strong>STEMI<\/strong> \u00e0\nPrimary PCI with or without stent placement is the procedure of choice for all STEMI\nas well as high-risk NSTEMI patients who present within 12 hours. <\/li><\/ul><ul><li><strong>Prasugrel + aspirin is the antiplatelet regimen most commonly\nselected for patients who are to undergo PCI.<\/strong> <\/li><\/ul><ul><li>Prasugrel acts rapidly and more\npredictably than clopidogrel. Prasugrel is also preferred over clopidogrel in diabetics.\n<\/li><\/ul><ul><li>The GPIIb\/IIIa antagonists are\nthe most powerful antiplatelet drugs; they are combined with aspirin for high-risk\npatients undergoing PCI.<\/li><\/ul><ul><li>Prasugrel is used when stent\nthrombosis occurs during clopidogrel treatment.<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li><strong>Cerebrovascular disease<\/strong> <ul><li>aspirin has reduced the\nincidence of TIAs and stroke in patients with TIAs. <\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li><strong>Prosthetic heart valves and arteriovenous shunts<\/strong> <ul><li>Antiplatelet drugs used with\nwarfarin reduce the formation of microthrombi on artificial heart valves and\nthe incidence of embolism.<\/li><\/ul><\/li><li><strong>Venous thromboembolism<\/strong> <ul><li>Anticoagulants are routinely\nused in DVT and PE. <\/li><\/ul><ul><li>Trials have shown antiplatelet\ndrugs also to have a prophylactic effect, but their relative value in comparison\nto, or in addition to anticoagulants is not established; they are infrequently\nused.<\/li><\/ul><\/li><li><strong>Peripheral vascular disease <\/strong><ul><li>Aspirin\/clopidogrel may produce\nsome improvement in intermittent claudication and reduce the incidence of\nthromboembolism.<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>Current usage<\/strong><\/p>\n\n\n\n<p>The use of\nantiplatelet therapy (including ASA, aspirin) for stroke prevention in AF is\nincreasingly limited:<\/p>\n\n\n\n<ul><li>Although antiplatelet agents\nreduce the risk of stroke in patients with AF, they are less effective than\nanticoagulant therapy<\/li><li>In the AVERROES study, apixaban\nwas superior to ASA for stroke prevention and was associated with a similar\nrate of major bleeding<\/li><\/ul>\n\n\n\n<p><strong>Guideline recommendations<\/strong><\/p>\n\n\n\n<p>Recent guidelines\nhave highlighted the limited risk-benefit of antiplatelet therapy for stroke\nprevention based on the efficacy profile and potential for causing serious\nbleeding events:<\/p>\n\n\n\n<ul><li>American College of Chest\nPhysicians (ACCP) 2012 guidelines limit the recommendation for ASA to an option\nfor patients with AF with a low risk of stroke (although oral anticoagulation\nis preferred), or patients with AF and no stroke risk factors (with no\nantithrombotic therapy preferred over ASA therapy)<\/li><li>ESC 2016 guideline update:\nAntiplatelet therapy is not recommended for stroke prevention in patients with\nAF<\/li><li>In contrast, the American Heart\nAssociation\/American College of Cardiology\/Heart Rhythm Society (AHA\/ACC\/HRS)\n2014 guidelines for the management of patients with AF still include ASA as an\noption for patients with a moderate risk of stroke<\/li><\/ul>\n\n\n\n<p><strong>2016 ACC\/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease<\/strong><\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"718\" height=\"485\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-42.png?w=718\" alt=\"\" class=\"wp-image-191\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-42.png 718w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-42-300x203.png 300w\" sizes=\"(max-width: 718px) 100vw, 718px\" \/><\/figure><\/div>\n\n\n\n<p>Patients with a\nhistory of ACS &gt; 1-year prior who have since remained free of recurrent ACS\nare considered to have transitioned to SIHD. Arrows at the bottom of the figure\ndenote that the optimal duration of prolonged DAPT is not established.\nClopidogrel is the only currently used P2Y12 inhibitor studied in patients with\nSIHD undergoing PCI. Aspirin therapy is almost always continued indefinitely in\npatients with coronary artery disease. <\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp; *High bleeding risk denotes those who have\nor develop a high risk of bleeding (e.g., treatment with oral anticoagulant\ntherapy) or are at increased risk of a severe bleeding complication (e.g., major\nintracranial surgery). ACS indicates acute coronary syndrome; BMS, bare metal\nstent; CABG, coronary artery bypass graft surgery; DAPT, dual antiplatelet\ntherapy; DES, drug-eluting stent; Hx, history; MI, myocardial infarction; PCI,\npercutaneous coronary intervention; SIHD, stable ischemic heart disease; and\nS\/P, status post.&nbsp; <\/p>\n","protected":false},"excerpt":{"rendered":"<p>Anti-platelet agents interfere with platelet function and are useful in the prophylaxis of thromboembolic disorders In veins, due to sluggish blood flow, a fibrinous tail is formed which traps RDCs &#8216; the red tail &#8216;. In arteries, platelet mass is the main constituent of the thrombus. Antiplatelet drugs are, therefore, more useful in arterial thrombosis.[&#8230;]\n","protected":false},"author":3,"featured_media":190,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/189"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=189"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/189\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media\/190"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=189"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=189"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=189"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}