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Many astute clinicians use buy generic cytotec 100 mcg on-line medicine rash, and refer their patients to generic cytotec 200 mcg mastercard medications list form, websites such as Crediblemeds cost of cytotec denivit intensive treatment. Interrogation of implanted device memory can also provide an indicator of the success of drug therapy. In some patients, tachycardia episodes are infrequent enough (months between occurrences) and symptoms mild enough that reactive drug administration is more reasonable than chronic daily dosing. Adverse Effects Antiarrhythmic drugs produce one group of adverse effects related to excessive dosage and plasma concentrations that result in both noncardiac (e. This process is underway but 5 until completed, adverse event risk in this setting is characterized using the previous classification. Proarrhythmia Drug-induced or drug-exacerbated cardiac arrhythmias (proarrhythmia) constitute a major clinical 6 problem. Proarrhythmia can manifest as an increase in frequency of a preexisting arrhythmia, sustaining of a previously nonsustained arrhythmia (even making it incessant), or development of arrhythmias that the patient has not previously experienced. Proarrhythmic events can occur in as many as 5% to 10% of patients receiving antiarrhythmic agents; heart failure increases this risk. Deaths were equally distributed throughout the treatment period, indicating that another type of proarrhythmic response can occur sometime after the beginning of drug therapy. Such late proarrhythmic effects may be related to drug-induced exacerbation of the regional myocardial conduction delay caused by ischemia and to heterogeneous drug concentrations that can promote reentry. Although quinidine shares the antimalarial, antipyretic, and vagolytic actions of quinine, only quinidine has direct cellular electrophysiologic effects. The ultimate biologic effect of the drug in a given patient depends on heart rate, drug concentration, and which channels are more prominently affected. Because of decreased demand for quinidine, manufacturing had ceased for a time, with little remaining supply in many countries; with recent renewed demand for its use in patients with Brugada syndrome, for example, quinidine is more readily available. Quinidine exerts little effect on automaticity of the normal sinus node but suppresses automaticity in normal Purkinje fibers (Table 36. In patients with sinus node dysfunction, quinidine can further depress sinus node automaticity. Faster rates result in more block of sodium channels and less unblocking because a smaller percentage of time is spent in the rested state (use dependence). Isoproterenol can modulate the effects of quinidine on reentrant circuits in + humans. As noted, quinidine blocks the transient outward current I , which probably explains its efficacy in suppressing ventricular arrhythmiasto in Brugada syndrome (see Chapter 33). Quinidine induces vasodilation by blocking alpha-adrenergic receptors and can cause significant hypotension. Quinidine can be given intravenously if it is infused slowly, but intramuscular dosing should be avoided. Approximately 80% of plasma quinidine is protein bound, especially to alpha -acid glycoprotein. Both the liver and the kidneys remove quinidine; dose adjustments1 may be made to achieve appropriate serum concentrations. The usual oral dose of quinidine sulfate for an adult is 300 to 600 mg four times daily, which results in a steady-state level within about 24 hours (see Table 36. Because it crosses the placenta, quinidine can be used to treat arrhythmias in the fetus. Allergic reactions include rash, fever, immune-mediated thrombocytopenia, hemolytic anemia, and rarely, anaphylaxis. Side effects may preclude long-term administration of quinidine in 30% to 40% of patients. Many of these patients are also receiving digitalis or diuretics or have hypokalemia; women are more susceptible than men. This proarrhythmic effect during initiation of treatment is reproducible and because of this, the drug should not be taken on an intermittent basis. Therapy of proarrhythmia requires immediate discontinuation of use of the drug; magnesium given intravenously (2 g over 1 to 2 minutes, followed by an infusion of 3 to 20 mg/min) is the initial drug treatment of choice. Drugs that induce hepatic enzyme production, such as phenobarbital and phenytoin, can shorten the duration of action of quinidine by increasing its rate of elimination. Quinidine can elevate serum digoxin concentrations by decreasing its clearance and volume of distribution and the affinity of tissue receptors. The cardiac actions of procainamide on automaticity, conduction, excitability, and membrane responsiveness resemble those of quinidine (see Tables 36. In vitro, procainamide decreases abnormal automaticity, with less effect on triggered activity or catecholamine-enhanced normal automaticity. Because of decreased demand, availability of intravenous (but not oral) procainamide is limited in some areas. It does not produce alpha blockade but can result in peripheral vasodilation, possibly through antisympathetic effects on the brain or spinal cord, which can impair cardiovascular reflexes (e. Approximately 80% of oral procainamide is bioavailable; the overall elimination half-life of procainamide is 3 to 5 hours, with 50% to 60% of the drug eliminated by the kidneys and 10% to 30% metabolized by the liver (see Table 36. Increased age, congestive heart failure, and reduced creatinine clearance lower the clearance of procainamide and necessitate a reduced dosage. With this method, the plasma concentration falls rapidly during the first 15 minutes after the loading dose, with parallel effects on refractoriness and conduction. Oral administration of procainamide requires a 3- to 4-hour dosing interval at a total daily dose of 2 to 6 g, with a steady-state concentration being reached within 1 day. Frequent dosing is required because of its short elimination half-life in normal persons. For the extended-release forms of procainamide, dosing is at 6- to 12-hour intervals. Procainamide is used to treat both supraventricular and ventricular arrhythmias in a manner comparable to that of quinidine. Although both drugs have similar electrophysiologic actions, either drug can effectively suppress a supraventricular or ventricular arrhythmia that is resistant to the other drug. As with quinidine, prior treatment with beta or calcium channel blockers is recommended to prevent acceleration of the ventricular response during atrial flutter or fibrillation after procainamide therapy. However, it should be used with caution in patients with evidence of His-Purkinje disease (bundle branch block) in whom a ventricular pacemaker is not readily available. The drug also has diagnostic application when given intravenously (10 mg/kg over 5 to 10 minutes). Noncardiac adverse effects from administration of procainamide include rash, myalgia, digital vasculitis, and Raynaud phenomenon. Fever and agranulocytosis may be the result of hypersensitivity reactions, and the white blood cell and differential counts should be assessed at regular intervals. Toxic concentrations of procainamide can diminish myocardial performance and promote hypotension.
However cheap cytotec online mastercard treatment of hyperkalemia, an angiographic snapshot in time does not reflect the fluctuating status of flow in the infarct vessel discount cytotec 200 mcg overnight delivery treatment strep throat, which may undergo repeated cycles of patency and reocclusion before or during fibrinolysis purchase cytotec 200mcg visa symptoms 6 days before period. To provide a more quantitative statement of the briskness of coronary blood flow in the infarct artery and to account for differences in the size and length of vessels (e. The terms myocardial “no-reflow” and “coronary microvascular obstruction” 42 describe a state of reduced myocardial perfusion after opening of an epicardial infarct-related artery. The four major impediments to normalization of myocardial perfusion are ischemia-related injury, reperfusion-related injury, distal embolization, and individual susceptibility of the microcirculation to 42 injury (Fig. Obstruction of the distal microvasculature in the downstream bed of the infarct- related artery results from platelet or microparticle microemboli and thrombi. Fibrinolysis may actually exacerbate microembolization of platelet aggregates because of the exposure of clot-bound thrombin, an extremely potent platelet agonist. Spasm can also occur in the microvasculature as a result of the release of substances from activated platelets. Reperfusion injury results in endothelial cell edema, production of reactive oxygen species, and calcium overload. In addition, cytokine activation leads to the accumulation 42 of neutrophils and inflammatory mediators that contribute to tissue injury. Interstitial edema from ischemia and reperfusion injury can compress vasculature, further compromising perfusion. Complete reperfusion requires successful restoration of normal flow in both the epicardial coronary artery and the distal coronary microvasculature, termed myocardial tissue–level reperfusion. Failure of epicardial reperfusion can result from failure to induce a lytic state or from persistent mechanical obstruction at the site of occlusion. Failure of microvascular reperfusion is caused by a combination of platelet microthrombi followed by endothelial swelling and myocardial edema (“no reflow”). Successful reperfusion requires a patent artery with an intact microvascular network. Defects in perfusion patterns seen with myocardial contrast-enhanced echocardiography correlate with regional wall motion abnormalities and lack of myocardial viability on dobutamine stress 48 echocardiography (see Chapter 14). A reduction in mortality is seen if the dye enters the microvasculature but is still persistent at the end of the washout phase (grade 2). The lowest mortality rate is observed in patients with normal perfusion (grade 3), with the dye being minimally persistent at the end of the washout phase. Analysis of six time categories from the onset of symptoms to randomization showed a nonlinear relationship of treatment benefit to time, with the best outcome 1 occurring in the first 1 to 2 hours after the onset of symptoms. Absolute mortality rates are shown for the fibrinolytic and control groups in the center of the figure for each of the clinical features at initial encounter, listed on the left side of the figure. This translates to a reduction of 18 deaths per 1000 patients treated with thrombolytic agents. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of mortality and major morbidity results from all randomized trials of more than 1000 patients. Modeling of mortality risk cannot cover all clinical scenarios, however, and should supplement clinical judgment in individual cases. The short-term survival benefit enjoyed by patients who receive fibrinolytic therapy endures after 1 to 10 years. All fibrinolytic agents exert their effect by converting the proenzyme plasminogen to the active enzyme plasmin. The so-called fibrin-specific fibrinolytics are those that are relatively inactive in the absence of fibrin but in its presence substantially increase their activity on plasminogen (see Chapter 93). Streptokinase, a protein derived from streptococci, binds and activates human plasminogen and is an inexpensive and effective fibrinolytic agent that is still used in some regions of the world. The myocardial salvage index, defined as the difference between the initial perfusion defect (e. Complications of Fibrinolytic Therapy Bleeding complications are most common, and intracranial hemorrhage is the most serious complication of fibrinolytic therapy; its frequency is generally less than 1% but varies with the clinical characteristics 1 of the patient and the fibrinolytic agent used (Fig. Common risk factors include increased age, low body weight, and hypertension on admission. Intracranial hemorrhage associated with thrombolytic therapy for elderly patients with acute myocardial infarction: results from the Cooperative Cardiovascular Project. However, this excess early mortality is more than offset by deaths prevented beyond the first day, with an average 18% (range, 13% to 23%) reduction in 1 mortality by 35 days compared with offering no reperfusion therapy. The mechanisms responsible for this early hazard are not clear but are probably multiple, including an increased risk for myocardial rupture, fatal intracranial hemorrhage, and possibly myocardial reperfusion injury. Recent exposure to streptococci or streptokinase produces some degree of antibody-mediated resistance to streptokinase (and anistreplase) in most patients. Choice of Agent The choice of fibrinolytic in hospital systems is generally driven by the desire to establish consistent protocols within the health care system by weighing ease of dosing, cost, and other institutional preferences. In patients who are to be treated with a fibrin-specific fibrinolytic, we believe that clinicians should use a bolus fibrinolytic such as reteplase or tenecteplase. Bolus fibrinolytics have a lower chance of medication errors and are associated with less noncerebral bleeding—as well as 4,53 offering the potential for prehospital treatment. Persistent chest pain late after the onset of symptoms correlates with a higher incidence of collateral or anterograde flow in the infarct zone and is therefore a marker for viable myocardium that might be salvaged. Because elderly patients treated with fibrinolytic agents more than 12 hours after the onset of symptoms have an increased risk for cardiac rupture, we believe that restricting late administration of a fibrinolytic to patients younger than 65 years with ongoing ischemia is preferable. Catheter-Based Reperfusion Strategies Catheter-based strategies can also achieve reperfusion of the infarct artery. This approach has evolved from passage of a balloon catheter over a guidewire in the culprit vessel only to now include potent oral antiplatelet therapy, multiple options for anticoagulants, and coronary stents, with the possibility of 1 multivessel revascularization. Surgical Reperfusion Providing surgical reperfusion in a timely fashion is usually not logistically possible. Selection of the optimal form of reperfusion therapy therefore involves judgments regarding both system resources and individual patient characteristics. The best estimate of the time delay at which this advantage is lost is 1 to 2 hours, but it may vary depending on the timing of initial evaluation and the extent of 67 myocardium at risk. The limited randomized trials evaluating a strategy of routine catheterization after fibrinolysis have provided mixed results. Nevertheless, overall, these trials have suggested improvement in clinical outcomes in patients transferred for early catheterization, particularly 1 those at higher risk for death and recurrent ischemia (Fig. Trials comparing routine early catheterization after fibrinolytic therapy with either an ischemia-driven approach or routine delayed catheterization generally showed a consistent pattern of benefit with a strategy of routine transfer for invasive evaluation. The darker bars represent patients who underwent routine early catheterization after fibrinolytic therapy. The lighter bars represent patients who underwent either an ischemia-guided or routine delayed catheterization approach. Although we believe that there will probably be continued benefit even beyond 24 hours in patients with a patent but stenotic infarct artery after initial successful reperfusion, later time windows have not been directly examined. This schematic view shows a longitudinal section of an infarct-related artery at the level of the obstructive thrombus. Following rupture of a vulnerable plaque (bottom center), the coagulation cascade activates, which ultimately leads to the deposition of fibrin strands; platelets also activate and begin to aggregate.
The thigh symp- • The needle is inserted cytotec 200mcg discount medicine hat weather, after prep and anesthetic over the toms are worsened by exercise such as running and kicking cheap cytotec american express medicine definition, inferior aspect of the obturator foramen purchase 200mcg cytotec free shipping treatment hyponatremia. These symptoms • Peripheral nerve stimulation may be used to determine may be falsely attributed to hip joint pathology. Physical Examination Ultrasound Guidance The patient will demonstrate weakness of the adductor mus- • The patient is placed in the supine position with thigh cles and may walk with a rolling gait due to external rotation externally rotated. Patients may have focal tenderness of the medial • The high-frequency linear probe is placed transversely at thigh in the adductor canal with deep palpation. Pain may the femoral crease, and the femoral neurovascular bundle also be exacerbated by forcible extension and internal rota- is identifed . Electrodiagnostic tests will • The probe is moved medially toward the pubic tubercle demonstrate denervation changes of the adductor muscles. Given the small space and tight lig- abnormal gait, and inability to evert the ankle due to pero- aments of the area, low volumes should be injected. Patients may have positive Tinel’s sign over the neck of the fbula and pain with resisted inver- sion of the ankle. Technical Aspects Diagnosis Blind Technique Tarsal tunnel syndrome presents with pain in the medial • Patient position is lateral with the medial foot exposed. The pain is • After prep, the posterior tibial artery is identifed between typically neuropathic in nature and may be worst at the ball medial malleolus and Achilles tendon. Pain is often worse with activity and prolonged • A 25- or 27-gauge needle is inserted posterior to the artery standing and may feel worse at night despite elevation. Patients have increased risk of falls due to foot numbness • A small volume of local anesthetic is injected. On physical examination, a Tinel’s sign may be elicited behind Ultrasound Guided the medial malleolus. Tenderness to palpation may also be • Ultrasound guidance improves the success rate of this noticeable in that area. Motor impairment of the intrinsic muscles of the fexor retinaculum with the medial malleolus at one edge. Differential Diagnosis • A 25- or 27-gauge needle may be inserted using either in- • Plantar fasciitis plane or out-of-plane approach, taking care to avoid vas- • Achilles tendonitis culature and injecting small volumes of local anesthetic. This condition is named after Thomas • The tibial nerve gives off motor branches in the thigh and Morton, one of the frst physicians to report it in 1876 . The common digital nerves are vulnerable to injury as they pass under the deep The tarsal tunnel runs along the posterior medial aspect of transverse metatarsal ligament. The nerves become entrapped the ankle and foot, bounded by the talus, navicular bone, and in perineural fbrosis. The tarsal tunnel contains: toe extension due to ballet or high-heeled shoes . The pain is neuropathic in type, with both sharp and burning sensations described on the sole Side Effects and Complications of the foot and toes. The patient may describe altered sensa- tion on the sole of the foot and may fnd walking barefoot on The side effects of lower extremity nerve blocks include the a hard surface painful. The pain is worse with walking and common risks of bleeding, hematoma, infection, and nerve exercise and better with rest and elevation. Some injections, such as those of the genitofemo- There may be a tender point in the interspace between ral nerve, risk injury to the spermatic cord or other delicate toes. Injections of the obturator nerve risk space with the fngers of one hand while laterally compress- injury of the femoral artery. The entrapped areas such as the tarsal tunnel may worsen symptoms via nerve may pop out from the metatarsals with a palpable click compression unless small injection volumes are used. Epinephrine or other vasoconstric- • The digital nerves originate from the terminal branches of tors may cause vasoconstriction of the small vessel or local the posterior tibial nerve: the calcaneal, lateral, and medial ischemia. The lower extremities are a frequent site for the develop- tar intrinsic muscles and sensory innervation of the plan- ment of mononeuropathies, second only to forearms and tar anterior foot and second to ffth toes. Knowledge of the sensory and motor distributions of nerves is the best guide to diagnosis, with imaging and Technical Aspects electrodiagnostic testing mainly serving to confrm diagnoses. Many of these procedures resemble regional anesthesia • With the patient’s leg extended and ankle dorsifexed, a techniques; however, the volume of local anesthetic uti- 27-gauge short needle is advanced after prep from dor- lized should be lower in most cases for diagnostic nerve sum toward the plantar surface of the interspace, aiming blocks. Knowledge of the regional anatomy is essential for safe • A small amount of local anesthetic (1–2 mL) is injected injection. Some injection sites are superfcial and adjacent to bony • Alternatively, the blind injection may be performed with structures. This raises the risk of skin atrophy and makes the feet dorsifexed and the needle directed parallel to good technique and infltration of anesthetic important for the toes into the inferior part of the painful interspace. These Ultrasound Guidance structural constraints limit the volume of injectate that • The patient is placed in the supine position with the can be safely used. Ultrasound-guided interventional procedures for • With lateral compression of the metatarsals, the structure patients with chronic pelvic pain – a description of techniques and should be seen to sublux in a plantar direction. An audit of our quency ablation of the genital branch of the genitofemoral nerve for experience (1998–2008). A peculiar and painful affection of the fourth metatarso- nerve during spine surgery. Since then, multiple techniques and multiple connections to general sensory fbers of the head and outcomes have been described [7–45]. This took into consideration the bene- – Oral pain fts versus risks, methodological quality of supporting – Sphenopalatine neuralgia evidence, and implications (Table 33. The available evidence is classifed as 2C+: effectiveness only demonstrated in Preoperative Evaluation observational studies; given there is no conclusive evi- dence of the effect, benefts closely balance with risk and • Evaluate patient for anticoagulant or antiplatelet ther- burdens. It is located in the pterygopala- preganglionic sympathetic fbers comprise the tine fossa near the sphenopalatine foramen posterior to white rami communicantes ascending through the foramen rotundum and anterior to the pterygoid the sympathetic chain into the superior cervical canal (Figs. This should span the area posteriorly Intranasal Approach from the nose toward the ear and inferiorly from the zygo- matic arch toward the mandible. Leave the ipsilateral eye • The advantage of this approach is that it may be done in exposed. The needle is then advanced until the tip is in the fossa, adjacent to • The patient is placed in the supine position, and the palatine bone. Day • Using a sterile scalpel, the tip of the sheath is cut obliquely • At the level of the conch, the spinal needle tip should be at 45° creating a sheath bevel to expose 2 mm of the spi- positioned near the posterolateral wall of the nasal cavity nal needle tip (Fig. Paresthesia at the root of the nose should be described by the patient at less than 1. Redirect the needle cephalad and head and to the internal carotid plexus without synapses. Reproducible pain-relieving diagnostic blocks should be • Stimulation of the maxillary nerve causes paresthe- performed under fuoroscopy before proceeding to radio- sia in the upper teeth. Complications documented include epistaxis, local or retro- orbital hematoma, infection, refex bradycardia, and tran- • Relative sient hypesthesia or anesthesia of the palate or pharynx. Nose, nasal cavity, paranasal sinuses and peterog- • Refex bradycardia has been reported with the use of opalatine fossa.
Determining the precise time of onset of the infarction process in these patients cytotec 200mcg with visa medications resembling percocet 512, however generic cytotec 100 mcg fast delivery symptoms 9 days before period, can be difficult and sometimes misleading order 200 mcg cytotec amex treatment ulcer. In such patients with waxing and waning ischemic discomfort, a rigid time interval from the first episode of pain should not be used when determining whether a patient is “outside the window” for benefit from acute reperfusion therapy. Pathophysiology of Myocardial Reperfusion Prevention of cell death by restoration of blood flow depends on the severity and duration of the preexisting ischemia. They provide sufficient perfusion of myocardium to slow cell death and probably have greater importance in patients undergoing reperfusion later than 1 to 2 hours after coronary occlusion. Even after successful reperfusion and despite the absence of irreversible myocardial damage, a period of 24 postischemic contractile dysfunction can occur—a phenomenon called myocardial stunning. Reperfusion Injury Reperfusion, although beneficial in terms of myocardial salvage, may cause adverse sequelae described 25 by the term reperfusion injury (see Chapter 58). The concept of lethal reperfusion injury to potentially salvageable myocardium remains controversial, both in 30-32 animals and in humans. Microvasculature damage in the reperfused myocardium can lead to a hemorrhagic infarct (see Chapter 58). Fibrinolytic therapy appears more likely than catheter-based reperfusion to produce hemorrhagic infarction. Although there is concern that this hemorrhage may lead to extension of the infarct, this does not appear to be the case. Histologic study of patients not surviving despite successful reperfusion has revealed hemorrhagic infarcts, but this hemorrhage does not usually extend beyond the area of necrosis. Also, using antiplatelet agents and antithrombins to minimize embolization of atheroembolic debris, and prevention of subsequent inflammatory damage may serve to maintain microvascular integrity (see Tables 60. The effectiveness of interventions directed against reperfusion injury appears to decline rapidly the later that they are administered after reperfusion. In animals, no beneficial effect is detectable after 45 to 60 minutes of reperfusion has elapsed. An alternative experimental approach to protection against reperfusion injury is called postconditioning, which involves introducing brief, repetitive episodes of ischemia alternating with 25,33 reperfusion. This appears to activate the cellular protective mechanisms centering around prosurvival 25 kinases. Many of these protective kinases are also activated during ischemic preconditioning. Reperfusion Arrhythmias Transient sinus bradycardia occurs in many patients with inferior infarcts at the time of acute reperfusion, often accompanied by some degree of hypotension. This combination of hypotension and bradycardia with a sudden increase in coronary flow may involve activation of the Bezold-Jarisch reflex. When present, rhythm disturbances may actually indicate successful restoration of coronary flow, but their specificity for successful reperfusion is limited. In general, clinical features are inaccurate markers of reperfusion, with no single clinical finding or constellation of findings being reliably predictive of 1 angiographically demonstrated coronary artery patency. Although reperfusion arrhythmias may show a temporal clustering at restoration of coronary blood flow in patients after successful fibrinolysis, this brief “electrical storm” is generally innocuous and therefore does not warrant prophylactic antiarrhythmic therapy or specific treatment, except in rare cases of symptomatic or hemodynamically significant 1 reperfusion arrhythmias. Late Establishment of Patency of the Infarct Vessel The improved survival and ventricular function after successful reperfusion may not result entirely from limitation of infarct size. Poorly contracting or noncontracting myocardium in a zone that is supplied by a stenosed infarct-related artery with slow anterograde perfusion may still contain viable myocytes. Patients treated within the first 1 to 2 hours after the onset of symptoms 1 seem to have the greatest potential for long-term improvement in survival with fibrinolysis. Platelets that aggregate with incorporation of relatively few red cells form a white thrombus. The mesh of fibrin strands and platelet aggregates obstructs flow in the infarct-related artery. Pharmacologic reperfusion is a multipronged approach consisting of fibrinolytic agents that digest fibrin, anticoagulants that prevent the formation of thrombin and inhibit the activity of formed thrombin, and antiplatelet therapy. Nevertheless, a meta-analysis of trials in the fibrinolytic era suggested that for every 1000 patients treated with heparin versus aspirin alone, five fewer deaths (P = 0. The most serious complication of anticoagulant therapy is bleeding (see Chapter 93), especially intracranial hemorrhage. In addition, both hirudin and bivalirudin cause higher rates of major bleeding than heparin when used with 74 fibrinolytic agents. Treatment with bivalirudin significantly 72 reduced mortality at 30 days and at 1 year, but increased the early risk for stent thrombosis. Overall, bivalirudin-based regimens lowered the risk of major bleeding (risk ratio, 0. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. A, Treatment with bivalirudin was associated with significantly lower rates of major bleeding and mortality at 30 days. C, Acute stent thrombosis during the first 24 hours was higher in patients treated with bivalirudin alone, but cardiovascular mortality was reduced in the bivalirudin group after 1 year of follow-up, thus providing strong evidence for this treatment strategy. The dashed vertical line indicates the comparison at day 2 (direct pharmacologic comparison), at which time a trend in favor of enoxaparin was seen. Individual outcomes of all-cause death, reinfarction, and major bleeding through 7 days are shown. In patients with a known history of heparin-induced thrombocytopenia, bivalirudin in conjunction with 1 streptokinase is a useful alternative to heparin. Antiplatelet Therapy Platelets play a major role in the response to disruption of coronary artery plaque, especially in the early phase of thrombus formation. Fibrinolysis can activate platelets, and platelet-rich thrombi resist fibrinolysis more than fibrin and erythrocyte-rich thrombi (eFig. In contrast to the observations of a time-dependent mortality effect of fibrinolytic therapy, the reduction in mortality with aspirin was similar in patients treated within 4 hours (25% reduction in mortality), between 5 and 12 hours (21% reduction), and between 13 and 24 hours (21% reduction). The reduction in mortality was as high as 53% in patients who received both aspirin and streptokinase within 6 hours of symptoms. Inhibitors of the P2Y12 adenosine diphosphate receptor help prevent the activation and aggregation of platelets. Thus it appears that clopidogrel did not increase the rate of complete opening of occluded infarct arteries when fibrinolysis was administered, but was effective in preventing reocclusion of an initially reperfused infarct artery. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Patients in the clopidogrel group had a lower rate of the composite endpoint of death, reinfarction, or stroke (9. However, subsequent large outcomes trials revealed no significant effect on 79 survival, and reductions in reinfarction were outweighed by the increases in bleeding. Prasugrel reduced definite or probable stent thrombosis by 42% compared with clopidogrel. If true aspirin allergy is present, other antiplatelet agents such as clopidogrel or ticlopidine can be substituted.