Posterior Cerebral Artery Stroke

Posterior cerebral artery (PCA) stroke is less common than stroke involving the anterior circulation. An understanding of PCA stroke phenomenology and mechanisms requires knowledge of neurovascular anatomy and of the structure-function relationships of this region of the brain. Identifying mechanisms of stroke is essential so that appropriate preventive therapies may be instituted. This article provides an overview of PCA stroke and focuses exclusively on stroke of arterial origin involving the PCA territory (see the images below). (See Anatomy, Pathophysiology, Etiology, Treatment, and Medication.)

Unenhanced head computed tomography (CT) scan demonstrating a subacute L posterior cerebral artery (PCA) infarct.

Computed tomography (CT) scan of the brain showing hypodense areas in the right occipital lobe consistent with a recent posterior cerebral artery (PCA) ischemic infarct.

Ischemic strokes occur when blood cannot flow to cerebral structures. Neuron metabolism tolerates a brief period of interrupted oxygen and glucose delivery. Cell death is imminent after approximately 6 minutes of halted blood circulation. Large cortical neurons are especially sensitive to ischemia. Infarcts include a central area, or umbra, of highly concentrated cell death, surrounded by a penumbra of tissue containing stunned cells that may recover, assuming circulation is reestablished or produced through nearby collaterals. (See Pathophysiology and Etiology.)

Patients who have sustained PCA strokes present with an interesting and diverse spectrum of neurologic symptoms. The most common long-term sequelae of PCA strokes are visual and sensory deficits. In general, patients with PCA distribution strokes exhibit less overall chronic disability than do those with anterior cerebral, middle cerebral, or basilar artery infarctions. (See Prognosis and Presentation.)

Active neurorehabilitation of patients following cerebrovascular accident is essential because evidence suggests that prolonged neural plasticity follows stroke. Active intervention, especially by a team of rehabilitation specialists, is beneficial, increasing the probability of the patient's achieving maximal independence in activities of daily living (ADL). The role of the physiatric clinician on the neurorehabilitation team is to avert medical complications and facilitate integration of the various therapeutic services. (See Treatment.)

Complications

Stroke complications include the following (see Prognosis, Presentation, and Workup):

• Recurrent ischemic event[1]

• Hemorrhage into infarcted brain tissue

• Stroke-associated epilepsy

• Anticoagulation-associated intracranial, gastrointestinal, or retroperitoneal hemorrhaging

• Urinary tract and pulmonary infections

• Skin breakdown

• Depression

• Chronic pain

• Dyskinesia and dystonia

Common neurovascular anatomy

The posterior cerebral arteries (PCAs) are paired vessels, usually arising from the top of the basilar artery and curving laterally, posteriorly, and superiorly around the midbrain. The PCAs supply parts of the midbrain, subthalamic nucleus, basal nucleus, thalamus, mesial inferior temporal lobe, and occipital and occipitoparietal cortices. In addition, the PCAs, via the posterior communicating arteries (PCOM), may become important sources of collateral circulation for the middle cerebral artery (MCA) territory.

Various nomenclature methodologies have been used to describe PCA vascular anatomy. The PCA is divided into P1 and P2 segments by the PCOM. Penetrating branches to the mesencephalon, subthalamic, basal structures, and thalamus arise primarily from the P1 segment and the PCOM. These penetrating arteries include the thalamogeniculate, splenial (posterior pericallosal artery), and lateral and medial posterior choroidal arteries.

The P2 segment bifurcates into the posterior temporal artery and the internal occipital artery. The posterior temporal artery further divides into anterior, middle, posterior, and hippocampal branches. The internal occipital artery divides into calcarine and occipitoparietal branches.

Anatomic localization of the point of vascular occlusion in PCA infarcts may be simplified into the following 2 categories: (1) deep or proximal PCA strokes, causing ischemia in the thalamus and/or midbrain, as well as in the cortex; and (2) superficial or distal PCA strokes, involving only cortical structures.[2, 3]

Normal variants of neurovascular anatomy

The fetal PCA variant is seen in up to 30% of people, with incidence depending on how the variant is defined. The variant occurs when the P1 segment is congenitally absent or markedly hypoplastic and the PCA arises directly from the ipsilateral internal carotid artery (ICA). This can have diagnostic importance, in that PCA territory stroke may be caused by atheromatous disease of the anterior circulation (ie, ipsilateral carotid bulb atheroma).

The central artery of Percheron variant is uncommon and occurs when the bilateral medial thalamic/rostral midbrain perforators arise from a single trunk from one P1 segment. Occlusion may result in bilateral paramedian thalamic and rostral midbrain infarction. This is an example in which a single cerebral artery supplies bilateral structures.

Major PCA stroke syndromes

The major posterior cerebral artery (PCA) stroke syndromes (many of which occur concomitantly) include the following:

• Paramedian thalamic infarction

• Visual field loss

• Visual agnosia

• Balint syndrome

• Prosopagnosia

• Palinopsia, micropsia, and macropsia

• Disorders of reading

• Disorders of color vision

• Memory impairment

• Motor dysfunction

Paramedian thalamic infarction

This syndrome results from bilateral medial thalamic infarction. The presentation in these patients varies from lethargic to obtunded to comatose, but some patients may be agitated and may have associated hemiplegia or hemisensory loss. Occasionally, the cranial nerve III nucleus is involved, with resultant ophthalmoplegia.

Patients may take days to weeks to recover and seem to be in a sleeplike state. Although alertness generally returns, prognosis for good functional recovery is poor because of severe memory dysfunction.

The syndrome may result from a “top of the basilar” artery embolus. The artery of Percheron may be involved.

Visual field loss

Unilateral infarction produces homonymous hemianopia. Sparing of the macula is encountered frequently in infarction of the occipital lobes due to PCA occlusion. Macular sparing may be caused by collateral vascular supply to the macular region or by the very large macular representation in the occipital cortex; additionally, bilateral representation of macular vision has been suspected.

Bilateral infarctions of the occipital lobes produce varying degrees of cortical blindness depending on the extent of the lesion. Patients often exhibit Anton syndrome, a state in which they fervently believe they can see when they cannot. Patients may describe objects that they have not seen previously in exquisite detail, completely in error and oblivious to that error.

Another intriguing phenomenon is blindsight. Although cortically blind, patients can respond to movement or sudden lightening or darkening of their environment.

Infarction of the lateral geniculate nucleus may produce hemianopia, quadrantanopia, or sectoranopia. The vascular supply is dual; the anterior choroidal artery supplies the anterior hilum and anterolateral areas, and the posterior choroidal artery supplies the rest. Occlusion of the posterior choroidal artery may produce a distinct syndrome of hemianopia, hemidysesthesia, and memory disturbance due to infarction of the lateral geniculate, fornix, dorsomedial thalamic nucleus, and posterior pulvinar.

Visual agnosia

This refers to a lack of recognition or understanding of visual objects or constructs. It is a disorder of higher cortical function.

The strict diagnosis of visual agnosia requires intact visual acuity and language function. Most patients have bilateral lesions, sparing the visual cortex but disrupting or disconnecting visual information; this interferes with the information’s ability to reach parts of the visual association cortex, for reference to visual memories. The patient with visual agnosia can recognize objects presented to a nonvisual sensory system; for example, the patient can identify keys by palpating them or hearing them jingle.

True visual agnosia has been divided into apperceptive and associative subtypes. In apperceptive visual agnosia, patients cannot name objects presented to them, draw objects from memory, or identify or match objects, yet they can see and avoid obstacles when ambulating and detect subtle changes in light intensity.

In associative agnosia, patients can draw objects to command and can match them or point to them, but they cannot name them. Patients can see shapes and reproduce them in drawings, yet they do not recognize the identity of objects.

Balint syndrome

This may occur with bilateral parieto-occipital infarction, most often in the watershed between the PCA and middle cerebral artery (MCA) territories. It is a triad of visual simultanagnosia, optic ataxia, and apraxia of gaze, which are characterized as follows:

• Visual simultanagnosia - Implies an inability to examine a scene and integrate its parts into a cohesive interpretation; a patient can identify specific parts of a scene but cannot describe the entire picture

• Optic ataxia - Implies a loss of hand-eye coordination such that reaching or performing a motor task under visual guidance is clumsy and uncoordinated

• Apraxia of gaze - A misnomer describing a supranuclear deficit in the ability to initiate a saccade on command

Prosopagnosia

Prosopagnosia refers to an inability to recognize faces. Typically, this deficit results from bilateral lesions of the lingual and fusiform gyri; however, cases of unilateral nondominant-hemisphere lesions resulting in prosopagnosia have been reported.

Palinopsia, micropsia, and macropsia

These are illusory phenomena that are of uncertain pathophysiology. Palinopsia describes the persistence of a visual image for several seconds to days in a partially blind hemifield. Micropsia and macropsia describe situations where objects appear smaller or larger than expected.

Disorders of reading

Pure alexia may result from infarction of the dominant occipital cortex. Words are treated as if they are from a foreign language. Patients may retain the ability to formulate a word and its meaning if spelled out to them orally or if they trace the letters with their hand. Patients may then learn to read, albeit terribly slowly, in a letter-by-letter fashion, being unable to integrate multiple letter groups.

Classic alexia without agraphia was described by Dejerine in the late 19th century. In his case study, he emphasized a left occipital cortex lesion and also infarction of the splenium of the corpus callosum, which disconnected fibers from the right occipital lobe, preventing them from reaching the angular gyrus.

Rarely, the dominant-hemisphere posterior temporal lobe is supplied by the PCA. Damage to this area results in a Wernicke-type aphasia with associated dyslexia and right hemianopia due to concomitant left occipital infarction.

Disorders of color vision

Lesions of the lingual gyrus in the inferior occipital lobe may produce disorders of color perception. Testing with Ishihara plates reveals a deficit. Colors may be described as washed out or gray. This deficit usually occurs only in the contralateral visual field and is called hemiachromatopsia.

A related problem is color anomia, also called color agnosia, in which patients can perceive and match colors but cannot associate them with the proper color names.

Memory impairment

Infarction of the medial temporal lobe, fornices, or medial thalamic nuclei may result in permanent anterograde amnesia. Although traditionally, bilateral infarction has been thought to be required for amnesia, memory functions may be lateralized such that infarction of left-sided structures may have a more lasting impact on verbal function.

Older patients frequently have lasting short-term memory impairment from unilateral PCA territory infarction. In addition, diffusion-weighted Imaging in patients with transient global amnesia has demonstrated lesions in unilateral temporal lobes resulting in temporary amnesia.

Motor dysfunction

When the blood supply to the cerebral peduncles arises from perforators of the P1 segment, infarction may occur, resulting in hemiplegia or hemiparesis. The clinical syndrome is no different from capsular infarction but often includes concomitant hemianopia because of occipital lobe involvement. The syndrome may mimic a large middle cerebral artery (MCA) infarction.

Ischemic stroke occurs when a region of cerebral blood flow is suddenly limited. This may occur by vessel occlusion or by relatively low flow. The rate of neuronal death varies with blood flow, variability in individual anatomy and collateralization, and inherent cerebral capacities (ie, some cerebral regions are more resistant than others).

Cerebral blood flow (CBF) rates of less than 20 mL/100 g/min may produce infarction depending on these individual differences plus the duration of oligemia, with lower CBF rates (< 10 mL/100 g/min) requiring less time to produce irreversible injury. Rapid restoration of blood flow is the most effective means of preserving brain tissue.

The mechanism of stroke involving the posterior cerebral artery (PCA) territory is variable. Common etiologic considerations for PCA stroke include the following:

• Cardiogenic embolization

• Atheromatous disease of proximal vessels - Results in occlusion and/or artery-to-artery embolization

• Dissection of proximal vessels - Results in occlusion and/or artery-to-artery embolization

• Intrinsic PCA atheromatous disease

Less common etiologies include migrainous cerebral infarction (which preferentially affects the PCA distribution), anterior circulation disease (when fetal PCA variant is present), hypercoagulable disorders, illicit substance use, vasculitides, and fibromuscular dysplasia.

Cardioembolism

Cardioembolism, which may arise from a number of different mechanisms, is the most common cause of PCA stroke. The most common cause of cardioembolism is atrial fibrillation, in which emboli form due to vascular stasis, frequently within the atrial appendage. Atrial fibrillation often represents a high-risk etiology for PCA stroke recurrence, particularly if the patient has other identified risk factors, including congestive heart failure, hypertension, age older than 75 years, diabetes mellitus, and prior stroke or transient ischemic attack. These risk factors are the basis of the CHADS2 score, which estimates the risk of recurrent stroke and suggests the benefit of oral anticoagulation based on score.[4]

Other sources of cardiogenic embolism include a mural thrombus on a hypokinetic wall segment (eg, postmyocardial infarction, dilated cardiomyopathy, ventricular aneurysm), endocarditis (bacterial, marantic, Libman-Sacks), prosthetic heart valve thrombosis, rheumatic heart disease, and paradoxical embolism via a patent foramen ovale or atrial septal defect.

Embolism may also arise from aortic arch atheroma. This entity has been elucidated by transesophageal echocardiography, which is more effective than transthoracic echocardiography in examining the aortic arch. Thickness of plaque greater than 4 mm or the presence of a mobile thrombus is strongly associated with stroke.

Proximal vertebrobasilar artery disease

Atheromatous disease may be found within the vertebral artery in patients with posterior circulation ischemia and may result in stenosis or occlusion of that proximal vessel. This may result in hypoperfusion or artery-to-artery embolism involving the PCAs.

Dissection of the vertebral arteries may result from trauma or occur spontaneously and result in arterial embolization. The vertebral arteries are uniquely prone to dissection due to their intracanalicular course within the vertebral bodies. (Some authorities have expressed concern that chiropractic manipulation of the neck may cause vertebral artery dissection.) PCA stroke secondary to vertebral artery dissection may occur when thrombus forms at an intimal tear and embolizes distally or when the dissection results in vessel stenosis/occlusion, with subsequent vascular stasis and embolism.

Intrinsic basilar atheromatous disease may result in misery perfusion or artery-to-artery embolization in the PCA distribution.

Intrinsic PCA stenosis from atherosclerosis is a less common, but recognized, cause of stroke.

Migrainous cerebral infarction

Migraine represents a particular challenge in stroke medicine. Migraine typically affects the posterior circulation, although the mechanisms by which stroke occurs are not known. However, numerous postulated mechanisms exist.

Migraine alone commonly results in focal neurologic deficits, which may include visual loss, language disturbances, vertigo, nausea/vomiting, and other symptoms suggestive of posterior circulation disease (frequently known as complicated or basilar migraine). Furthermore, stroke in the posterior circulation distribution is more commonly associated with headache, occurring in approximately 30% of patients. Therefore, distinguishing between complicated migraine, migrainous cerebral infarction, and stroke with headache may be challenging.

An estimated 5-10% of ischemic strokes in the United States involve the posterior cerebral artery (PCA) or its branches. While stroke is the third leading cause of death in the United States and the leading cause of adult disability, death from PCA stroke is uncommon and would more likely occur in the setting of concomitant brainstem infarction.

Race-, sex-, and age-related demographics

Stroke is more common in African Americans than in white or Hispanic populations in the United States.

Published data from the Tufts New England Medical Center posterior circulation stroke registry document that 58% of patients are male and 42% are female, with the mean age of stroke being 61.5 years.[5] Stroke incidence dramatically increases in the elderly population secondary to cardiovascular disease.

Mortality associated with isolated posterior cerebral artery (PCA) stroke is low; therefore, the prognosis is generally good. Visual field deficits improve to varying degrees; however, they may be permanent and associated with morbidity. Some neuropsychological deficits may improve with time but are also associated with morbidity.

On average, patients with posterior cerebral artery (PCA) stroke sustain minimal or no chronic motor disability. These patients are usually able to adapt to their visual deficit so that many ADL tasks are manageable.

Among young stroke victims, 30-70% return to work, with the higher fraction being men and those educated beyond high school.

In a single-blind cluster, randomized, controlled trial of stroke patients in acute stroke units, there was a decreased likelihood of death or dependence by 90 days after hospital admission in patients who received a multidisciplinary intervention focusing on evidence-based management of fever, hyperglycemia, and swallowing dysfunction, despite the severity of the stroke.[6]

Morbidity and mortality

Overall, the risk of death in patients with posterior cerebral artery (PCA) stroke is approximately 5% in the acute hospital setting. Most deaths occur in patients with deep or proximal PCA infarctions, particularly those involving bilateral midbrain and thalamic structures. Otherwise, most PCA infarctions result in chronic visual deficits (84%), sensory abnormalities (17%), and motor weakness (6%), as documented in the Brandt et al series of 127 patients.[7]

Recovery of visual field deficits may be limited; patients may be unable to drive or read, resulting in major limitations in their quality of life, despite normal motor function.

Other neuropsychological deficits may include prosopagnosia (inability to recognize faces), visual agnosia, amnesia, and alexia without agraphia. Rarely, PCA stroke results in infarction of the ipsilateral cerebral peduncle with resultant hemiplegia. Thalamic involvement can also produce contralateral sensory loss or chronic pain syndromes.

At discharge, all patients who have had a stroke should be counseled about the symptoms and signs of acute stroke. They should know that the major symptoms of stroke include the following:

• Sudden loss of vision

• Sudden loss of ability to speak or understand speech

• Sudden weakness on 1 side of the body

• Sudden loss of sensation on 1 side of body

• Sudden onset of incoordination

Since a delay in receiving emergency care is the major reason why patients cannot be treated with thrombolytic therapy, patients and their caregivers must be taught what to do if a stroke occurs. Patients should be instructed to call an ambulance (ie, call 911) if they or their friends/relatives suffer from any of the above symptoms.

For patient education information, see the Brain and Nervous System Center and the Cholesterol Center, as well as Stroke, High Cholesterol, and Cholesterol FAQs.

Patients with posterior cerebral artery (PCA) infarcts present for neurologic evaluation with symptoms including the following:

• Acute vision loss

• Confusion[8]

• New onset posterior cranium headache

• Paresthesias

• Limb weakness

• Dizziness

• Nausea

• Memory loss

• Language dysfunction[9]

The approach to stroke in the PCA territory is no different from the approach to stroke elsewhere in the brain. The immediate goals of assessment are to correctly identify stroke as a diagnostic possibility, appropriately localize the lesion, and determine the time of symptom onset. A high clinical suspicion of stroke can be supported when there is an acute onset of neurologic symptoms referable to a cerebral arterial distribution.

The phenomenology of PCA stroke is a function of the neuroanatomy and corresponding vascular supply; therefore, historical information may have a highly localizing value. PCA syndromes can be divided roughly into those involving the midbrain, thalamus, occipital cortex, medial temporal lobe, or occipitoparietal cortex or combinations of these.

Time of onset

Time of symptom onset needs to be precisely determined, as this may determine eligibility for acute stroke therapies. Rigorous questioning of the patient, family, or witnesses is often needed to clarify symptom onset.

If the patient is seen within 6-8 hours of onset, consideration may be given to various acute stroke therapies, including intravenous (IV) or intra-arterial (IA) thrombolysis. Mechanical endovascular therapies, which are increasingly used for various intracranial large vessel occlusions, have been described and may be considered but are infrequently used for PCA occlusion.

Risk factors

Once the appropriate acute therapies (if any) are instituted, the history should be directed at cerebrovascular risk factors and contributing historical elements that may reveal the underlying etiology. History should include past diagnoses (eg, diabetes mellitus, atrial fibrillation, hypertension), family history, social history, recent trauma to the head or neck, and a thorough review of systems.

Visual symptoms and headache

Because many individuals identify stroke with motor weakness or language loss, they may delay seeking medical care after experiencing only vision change or headache, unaware that a stroke has occurred.

Patients may report bumping into objects, hitting obstacles on the roadside, or not seeing half the printed page when reading.

Small, homonymous visual-field cuts often are mistaken for a loss or change of vision from 1 eye, attributable to a refractive error that is correctable with glasses.

A person with a hemifield visual loss and headache also may be discharged from urgent care with a diagnosis of migraine headache rather than of PCA stroke. A computed tomography (CT) scan easily can differentiate between both conditions. Additionally, a migraine is characterized by a moving, scintillating scotoma, not a fixed, bilateral, homonymous field cut.

The presence of homonymous hemianopia also helps in differentiating between a middle cerebral artery and PCA stroke, as profound hemiplegia or somatosensory loss may occur in both conditions.

A complete neurologic examination is essential in any patient presenting with acute neurologic symptoms and aids in confirming the diagnosis of stroke and localizing the disorder.

When patients present early and may be eligible for acute stroke therapies, a standardized and abridged examination is recommended. The National Institutes of Health (NIH) Stroke Scale is a validated assessment commonly used as a guide to patient selection for acute stroke therapies. The complete neurologic examination may follow the abridged examination when appropriate.

The physical examination should encompass a cardiologic and vascular examination, searching for arterial bruits, murmurs that suggest valvular heart disease, and signs of atrial fibrillation. Other physical stigmata, if seen, may demonstrate a propensity for atherosclerosis, including corneal arcus or tendinous xanthoma.

The most common examination finding is a homonymous visual-field cut, usually a complete hemianopia, caused by a lesion in the contralateral occipital lobe. Macular or central field sparing can occur if the occipital pole remains intact through blood supply from a branch of the middle cerebral artery. Cortical blindness results from bilateral posterior cerebral artery (PCA) infarcts.[7, 10]

Deep or proximal PCA infarcts involve portions of the thalamus and midbrain. Thalamic lesions result in contralateral face and limb sensory loss. The midbrain cerebral peduncle carries corticospinal tract fibers that decussate caudally in the brainstem. A peduncle lesion is associated with contralateral motor weakness. Motor symptoms also are induced by thalamic edema near the internal capsule or a focal lesion in this structure. The posterior aspect of the internal capsule, variably, receives some blood from branches off the proximal PCA.

Large or bilateral PCA infarcts that involve thalamus, temporal, and/or parietal-occipital lobes often result in a spectrum of possible findings (neuropsychologic deterioration and memory, language, or visual-cognitive dysfunction). Prosopagnosia and visual agnosia are representative examples.

Reviewing documentation and performing baseline neurologic examinations help the clinician to recognize an evolving or recurring stroke, which is treatable, from a completed infarction.

After stroke has been correctly identified and localized, the next step is to determine the mechanism by which the stroke occurred, as this will guide long-term preventive strategies. In some cases, all diagnostic possibilities need to be considered and the workup is extensive.

In other cases, however, the mechanism may be promptly suggested by the patient’s history, with a focused work-up revealing an immediate cause. An example would be a young individual with neck trauma in whom vascular imaging demonstrates a cervical artery dissection with thrombosis.

Essential components of workup in posterior cerebral artery (PCA) stroke depend on the patient's age, stroke risk factors, and prior medical history. For example, studies used to evaluate the older patient (whose stroke is associated with cardiovascular disease) may include those that assess (1) severe anemia or volume depletion that can cause, worsen, or confound cerebral ischemia; (2) early infection as a result of aspiration; and (3) baseline coagulation status in case treatment involves heparin, warfarin, or thrombolysis.

Strokes occurring in persons younger than 50 years require investigation for etiologies such as cardiac defects (patent foramen ovale), thrombophilia or hypercoagulable state (protein S or C or antithrombin III deficiency, activated protein C resistance, G20210A prothrombin mutation), arterial dissection, connective-tissue autoimmune disorders (antiphospholipid syndrome), and malignancy.

Identification of other stroke risk factors, including hypertension, diabetes, elevated cholesterol and lipid panels, and hyperhomocysteinemia, is also useful.

Evaluate patient's swallow function so that diet can be modified appropriately and aspiration pneumonia avoided.

Imaging

Imaging modalities that can be employed in the diagnosis and evaluation of PCA strokes include computed tomography (CT) scanning, CT angiography (CTA), single-photon emission CT (SPECT) scanning, magnetic resonance imaging (MRI), and MR angiography (MRA). Positron emission tomography (PET) scanning can be used to analyze neurometabolism in vivo; it is at present a research tool.

In the acute phase, routine blood tests should include a complete blood count (CBC), prothrombin time (PT)/activated partial thromboplastin time (aPTT)/international normalized ratio (INR), electrolytes, creatinine, and serum glucose. These tests are a part of the stroke mechanism work-up and are required to assess whether the patient is a candidate for acute stroke therapies.

When the mechanism of stroke is atherosclerotic disease, additional blood tests should be performed to assess atherosclerotic risk factors. Diabetes screening should be performed. A fasting serum cholesterol profile should be obtained.

Hypercoagulable disease workup

If the stroke mechanism is not evident from the medical history and routine workup, then special hematologic and serologic examinations should be considered, particularly in young patients with cryptogenic stroke. A full hypercoagulable workup should include assays for arterial thrombophilia, including antiphospholipid antibodies and lupus anticoagulant.

Additional assays for venous thrombosis may be obtained in the appropriate clinical setting (ie, patent foramen ovale with paradoxical embolism) and include protein C, protein S, factor V Leiden/activated protein C resistance, antithrombin III, and prothrombin gene polymorphism. Some of these assays give abnormal results in the setting of acute stroke or anticoagulant medications and may need to be obtained on a delayed basis. The use and value of hypercoagulable disorder assessments remains a somewhat imprecise and controversial area of stroke neurology.

All patients with suspected stroke should undergo emergent neuroimaging with CT scanning or MRI. An unenhanced head CT scan is usually performed, as this test is widely available, can be rapidly obtained, and is sensitive in identifying intracranial hemorrhage. (See the images below.)

Unenhanced head computed tomography (CT) scan demonstrating a subacute L posterior cerebral artery (PCA) infarct.

Unenhanced head computed tomography (CT) scan demonstrating hemorrhagic conversion of an ischemic stroke, approximately 72 hours after symptom onset.

An emergent CT or MRI scan is required prior to considering acute stroke therapies, including thrombolysis. CT scanning aids in the following:

• Identifying hemorrhage

• Identifying strokes that may be less acute than reported by patients - Ie, the presence of hypodensity suggests a more subacute than hyperacute process

• Identifying hyperdense vessels

• Excluding alternate diagnoses that may masquerade as stroke - Ie, neoplasm or other masses

CT scanning is less sensitive for lesions in the infratentorial region than the supratentorial region due to bony signal artifact and decreased tissue detail.

CT angiography

In the acute stroke setting, the use of CTA has greatly expanded. CTA can identify extracranial vascular disease (cervical atheromatous disease and dissection) and intracranial disease (intracranial stenosis or embolism). CTA results are frequently used to guide acute and chronic therapies, including medical, surgical, and endovascular treatments.

SPECT scanning

SPECT scanning is a nuclear medicine study using radioisotopes of technetium. It provides an analysis of relative blood flow by region, usually in the resting state. It is rarely useful in the clinical setting of acute stroke and can be considered a research tool.

MRI produces a much better examination of midbrain, subthalamic, and thalamic structures than CT scanning does. It also identifies acute stroke much earlier than does CT scanning, by highly sensitive, diffusion-weighted imaging. MRI offers various modalities that can aid in determining the age of the stroke, identify multiple or small lesions that would be missed on CT scans, and identify at-risk or penumbral tissue by way of perfusion imaging. (See the image below.)

Brain magnetic resonance imaging (MRI) scan demonstrating acute stroke. Diffusion restriction is seen on diffusion-weighted imaging.

Currently, the use of diffusion/perfusion imaging studies to identify mismatch (suggesting the presence of at-risk brain tissue that is not yet infarcted) is actively being studied, but it is not the accepted standard of care.

MRA is frequently used to assess the extracranial and intracranial vasculature, but it is more prone to artifact and tends to overestimate the degree of hemodynamic compromise within vessels. (See the image below.)

Magnetic resonance (MR) angiogram demonstrating bilateral fetal posterior cerebral artery (PCA) variants (black arrows) with the basilar artery terminating in bilateral superior cerebellar arteries (blue arrows).

Catheter cerebral angiography remains the criterion standard for evaluation of vascular anatomy. However, it is a more invasive method and does carry a small risk of procedure-related morbidity.

Increasingly, noninvasive methods of viewing the arterial anatomy (CTA, MRA, transcranial Doppler [TCD] ultrasonography) are being used; each has its own benefits, technical challenges, and limitations. In many cases, these noninvasive methods are sufficient for diagnosis and management. However, when they produce unclear findings or more information is needed about the vascular anatomy, angiography is required. In addition, angiography is required as a precursor to endovascular treatments. (See the images below.)

Digital subtraction angiogram demonstrating an acute L posterior cerebral artery (PCA) occlusion (red arrow) following balloon-assisted coiling of a basilar tip aneurysm.

Digital subtraction angiogram demonstrating revascularization of acute L posterior cerebral artery (PCA) occlusion (red arrow) during a balloon-assisted basilar tip aneurysm revascularization with use of balloon angioplasty.

Specific anatomical features of PCA aneurysms were identified by angiographic study of 81 patients with a diagnosis of 93 PCA aneurysms. In this anatomical study, 53 patients underwent computed tomography angiography, 49 underwent digital subtraction angiography, and 6 underwent magnetic resonance angiography. There were 29 ruptured and 64 unruptured PCA aneurysms. The distribution of the aneurysms along the PCA segments was P1 (N = 39; 9 ruptured), P1/P2 junction (N = 25; 9 ruptured), P2 (N = 21; 5 ruptured), and P3 (N = 8; 6 ruptured). The median aneurysm size was 7 mm for the ruptured aneurysms and 4 mm for the unruptured aneurysms. Saccular aneurysms (N = 69, 74%) had a typical projection for each location: P1 segment, upward (67%); P1/P2 junction, anterior/upward (80%); P2 segment, lateral (67%); and P3 segment, posterior (50%). Multiple aneurysms were seen in 43 patients. PCA aneurysms related to arteriovenous malformations were observed in 10 patients.[11]

TCD ultrasonography is not widely used in acute stroke; however, it may become useful as an adjunct in the diagnosis and acute treatment of stroke. TCD ultrasonography is dependent on the skill and experience of the operator. In skilled hands, the distal basilar and P1 and P2 segments can be assessed and may detect acute clot in the posterior cerebral artery (PCA).

Carotid duplex ultrasonography may be considered in PCA stroke when a fetal origin PCA is present. In this setting, carotid atheromatous disease would be symptomatic and patients may be considered for carotid endarterectomy or stenting for recurrent stroke prevention.

Echocardiography

Transthoracic echocardiography (TTE) is used routinely to investigate possible cardiac sources of embolus. Transesophageal echocardiography (TEE) is a more sensitive test. It is more effective than TTE at identifying valvular lesions, aortic arch atheroma, and interatrial shunts. Patent foramen ovale and any abnormal anatomy associated with it (such as atrial septal aneurysms) are more frequently detected by TEE.

Electrocardiography

All patients with stroke should have an immediate ECG. ECG may identify stroke mechanisms or stroke-associated conditions, such as myocardial infarction, conduction abnormalities, and atrial fibrillation.

The treatment approach to stroke is determined by localizing the problem (identifying the vascular territory involved) and subsequently by using the patient’s history, the stroke subtype, and investigational tools to discover the stroke mechanism. The medical treatment of stroke can be divided into acute (within 3-4.5 hours of stroke onset), subacute, and chronic phases.

If possible, patients with acute stroke should be cared for in a stroke unit by staff familiar with stroke etiology, workup, and treatment, and with poststroke complications. Patients may require intensive care unit (ICU) monitoring if they have a large-volume stroke, significant concomitant brainstem infarcts or tissue at risk, or significant comorbid medical conditions (ie, myocardial infarction) or if they have received acute stroke therapies.

The management of acute stroke in general may be complicated and extensive. Various considerations need to be made regarding issues such as management of hypertension, hyperglycemia, cerebral edema with increased intracranial pressure, hemorrhagic transformation of cerebral infarction, infections, aspiration, deep venous thrombosis, myocardial infarction, and other stroke-associated conditions.

Isolated posterior cerebral artery (PCA) stroke may not have all the attendant complications as the associated disability or volume of infarction may be less than with other stroke syndromes (eg, MCA or BA stroke syndromes).

Multidisciplinary approach

As previously mentioned, in a single-blind cluster, randomized, controlled trial of stroke patients in acute stroke units, there was a decreased likelihood of death or dependence by 90 days after hospital admission in patients who received a multidisciplinary intervention focusing on evidence-based management of fever, hyperglycemia, and swallowing dysfunction, despite the severity of the stroke.[6]

Experimental therapies

Many experimental treatment modalities such as cognitive retraining,[12] neuropharmacologic therapy (amphetamines),[13] robot-assisted physical and occupational therapy, and virtual environments[14] are reported to aid stroke recovery, but further evidence is needed to confirm their benefit.

Rehabilitation goals

Patients with acute posterior cerebral artery (PCA) infarcts generally are hospitalized, unless, due to late diagnosis, they can be seen safely on an outpatient basis. Aggressive rehabilitation begins once the patient is medically stable. Goals include maintaining range of motion, promoting active movement of the hemiplegic side if applicable, improving the patient's functional mobility and self-care capabilities, and monitoring medical conditions affecting recovery and prevention of further disability.

Activity

Activity restriction varies depending on the patient's deficits, but the patient should be encouraged to remain mobile if possible. At discharge, activities may be limited by neurologic deficits. The patient may be required to give up driving.

Management of mobility-related concerns

Painful contractures develop rapidly in weakened limbs and may impede recovery. Early and frequent performance of range of motion can help to prevent this problem.

Weakened patients may fall and suffer traumatic head injury or fractured hips. Close monitoring of patients with cognitive impairment and training of family is important.

Although deep venous thrombosis (DVT) is unusual in patients with isolated posterior cerebral artery (PCA) stroke, any patient who has diminished mobility from stroke (ie, concurrent brainstem stroke) or a comorbid condition should receive prophylactic therapy for DVT. This includes early mobilization, subcutaneous heparin, pneumatic pressure, and elastic stockings.

Decubitus ulcers develop rapidly in immobilized patients. Wet bedclothes facilitate skin breakdown. Attentive nursing care is essential.

Postdischarge pharmacotherapy

Discharge medications may include specific agents for stroke prevention (eg, aspirin, clopidogrel, warfarin) that usually are recommended by the neurologist prior to transfer to a neurorehabilitation setting. Cholesterol-lowering drugs, antihypertensive therapies, muscle relaxants, and substances for treating rare thalamic pain or chronic headaches or depression may be prescribed.

IV tissue plasminogen activator (tPA) may be given to patients who present within 3 hours of developing a disabling ischemic stroke. Because of the increased risk for complicating intracerebral hemorrhage, there are rigid guidelines for administering tPA.

In 2009, the American Heart Association/American Stroke Association (AHA/ASA) published a science advisory recommending that the time window for tPA administration be increased to 4.5 hours after a stroke, although this change has not been approved by the US Food and Drug Administration (FDA).[15] Research indicates that tPA is effective in patients even when administered within the 3- to 4.5-hour window,[16, 17, 18] but the AHA/ASA stated that, despite its recommendation, the effectiveness of tPA administration in comparison with other treatments for thrombosis, within that time period, is not yet known.

The eligibility criteria for treatment between 3 and 4.5 hours are similar to those employed for treatment prior to 3 hours, as established in the AHA/ASA's 2007 guidelines,[19] but with the exclusion criteria expanded to include any of the following patient characteristics:

• Age older than 80 years

• Use of oral anticoagulants

• Baseline NIH Stroke Scale score of greater than 25

• History of both minor stroke and diabetes

If a clear time of onset can be established, stroke in the PCA territory may be treated with IV TPA. However, because isolated PCA territory symptoms may be subtle or underappreciated, patients may mistake the time of stroke onset. Patients who experience significant motor, sensory, or language symptoms (middle cerebral artery [MCA] or basilar artery syndromes) are more likely to present urgently and with more precise time of onset. Administration of TPA beyond the recommended time limits likely offers no benefit to patients and exposes them to increased risk of intracerebral hemorrhage.

Angioplasty, stenting, mechanical embolectomy, and intra-arterial thrombolysis are enjoying ever-expanding application and use in acute stroke, although their roles continue to be defined. However, their application in the posterior cerebral artery (PCA) distribution is uncommon compared with other vascular distributions (internal carotid artery [ICA], middle cerebral artery [MCA], basilar artery, vertebral artery). This is likely due to the small size of the PCAs, low NIH Stroke Scale scores in which treatment benefit may be offset by procedural risk, delayed recognition of isolated PCA stroke syndromes, and other factors. Numerous mechanical embolectomy devices have been studied, and few have allowed or incorporated isolated PCA stroke for inclusion.

Endovascular therapies are more likely to be used if there is significant vertebrobasilar disease as the cause of PCA stroke or if the patient fails to respond to medical management. When the ICA is the source of stroke via a fetal PCA variant, surgical endarterectomy or endovascular stenting of the ICA may be appropriate.

More recently, treatments such as vertebral artery stenting have been used and may replace the medical-treatment-only approach to intrinsic vertebral artery disease.

In a study of treatment of 25 cases of PCA aneurysm, the authors found that treating PCA aneurysms with microsurgical or endovascular options can achieve comparable outcomes. In this study, endovascular treatment showed excellent anatomical and clinical outcomes for non-mass compressing, non-giant, saccular aneurysms. However, the authors noted that given the propensity for large-giant, dysplastic PCA aneurysms to develop in younger patients, microsurgical competence should be maintained. They also suggested that along with careful evaluation of the anatomic collaterals over the PCA territory, therapeutic parent artery sacrifice may be an appropriate option without adding bypass. There was no mortality in either group. Microsurgical treatment was the primary treatment in 15 aneurysms. Endovascular coil embolization was performed in 6 aneurysms, stent-assisted coil embolization in 2 aneurysms, and endovascular occlusion of the parent artery in 2 aneurysms.[20]

In unusual circumstances, vertebral artery bypass may be considered; however, this surgical procedure remains an unproven therapy. Extracranial (EC)-to-intracranial (IC) vertebral artery bypass may be undertaken by connection of the occipital artery to the vertebral, superior cerebellar, anterior internal carotid artery (ICA), or posterior ICA. The superficial temporal artery has also been used as a donor artery. Shunting to the posterior cerebral artery (PCA) may be accomplished by using veins or synthetic grafts. In general, EC-to-IC circulation shunting has been relegated to use in extenuating circumstances since the publication of the negative EC-IC bypass trial.[21]

Patients with posterior cerebral artery (PCA) stroke experience a dramatic alteration of visual function, requiring modification of ADL. Homonymous field loss makes these patients prone to burns, motor vehicle accidents, mechanical injury from falls, and walking into objects. Explain these risks clearly to the patient and his/her family. Do not allow driving until follow-up evaluations of visual-field loss have been completed and occupational therapists and clinicians have tested the patient for visual function. The patient must learn conscious scanning into the visual-field deficit.

The hemiparetic patient who has sustained a posterior cerebral artery (PCA) stroke must learn transfer techniques, walking with mechanical assistance (if feasible), and modified ADL (eg, dressing, bathing, cooking). Some patients require a significant amount of assistance. The patient's caregiver should meet with therapists to learn how best to help the patient at home without causing personal or other injury.

Depending on the degree of motor loss, available insurance coverage, and other variables, such as social situation, the patient may qualify for continued outpatient or home therapy.

Physical therapy

A small percentage of patients with a PCA infarct suffer chronic motor deficits. Approximately 5% of patients who do may require transfer, gait, and stair training with an assistive device. Orthotic devices (eg, ankle-foot orthosis) also may be beneficial.

Patients with PCA infarcts may demonstrate delayed postural reactions due to sensorimotor deficits. Programs designed to improve postural control and balance may be helpful.

Home exercise programs and family/caregiver training are important for sustaining improvement after discharge from therapy.[1]

Occupational therapy

The occupational therapist helps the patient adapt to homonymous hemianopia and visual-spatial function abnormalities. The patient benefits from scanning into the field deficit. A small percentage of patients who have suffered a PCA stroke require therapy for motor deficits of the upper limb.

Speech therapy

Speech therapy usually is not required for patients who have had a PCA stroke. However, in infrequent cases in which there is neuropsychological deterioration or memory-language deficits,[9] a speech therapist should be consulted.

Although dysphagia typically is not associated with PCA infarcts (unless there are concomitant brainstem infarcts), evaluation of swallowing may be useful in patients who may be at risk for aspiration.

Recreational therapy

Recreational therapy helps patients with posterior cerebral artery (PCA) stroke to adapt to visual deficits and facilitates a healthy affect (since depression is a common occurrence in stroke patients).

Acute stroke patients should undergo a bedside sips test to grossly assess for dysphagia (excepting those who have frank severe dysarthria/dysphagia or altered mental status).

A speech pathologist and dietitian may provide advice on diet immediately and in the long term. Enteral nutrition may need to be provided by alternative means, such as a nasogastric device or a percutaneous enteric gastrostomy tube in patients who have severe dysphagia. As mentioned previously, however, dysphagia is generally not an issue with PCA strokes unless there are concomitant brainstem infarcts.

Visual issues may need to be addressed, because patients may not be able to see one side of the plate and may neglect some of their food. In such cases, patients need to have the plate turned and must eventually be taught to turn their head to see the blind hemifield.

A heart-healthy diet is really an antiatherosclerosis diet and may be applicable depending on stroke mechanism and underlying risk factors. This prescription should be based on follow-up testing and investigation.

Stroke care is a multidisciplinary process. Participants may include a neurointensivist, a neurointerventionalist, a vascular surgeon, a neurologic surgeon, a stroke nurse specialist, a physical therapist, an occupational therapist, a speech therapist, a physiatrist or rehabilitation neurologist, and a case manager or social worker.

Ophthalmologists accurately plot visual-field loss in patients with posterior cerebral artery (PCA) stroke and can recommend corrective lenses and compensation techniques.

Pain specialists use many strategies to treat rare, intractable thalamic pain, including the employment of anticonvulsants (carbamazepine [Tegretol], gabapentin [Neurontin]) and tricyclic medications (amitriptyline [Elavil]). In addition, topiramate (Topamax) has been found to be helpful in treating headache and painful dysesthesias.

A psychiatrist may assist with treatment of mood disorders and psychotic symptoms. A neuropsychologist can help to assess and document cognitive function, which is especially important for persons returning to professional duties, considering living alone, or applying for disability.

Early attention to rehabilitation and eventual reintegration into the community speeds recovery and shortens the length of hospital stay.

Patients who have had a posterior cerebral artery (PCA) stroke should be observed on an outpatient basis to ensure that cerebrovascular risk factors are treated chronically, that changes in medication management following stroke are well tolerated, and that chronic disability is appropriately addressed.

Attention to rehabilitation should begin early. Involvement of a speech-language therapist may be required if alexia is present, with or without aphasia. An occupational therapist should be able to help teach patients to turn in order to view a blank visual hemifield.

An issue that frequently arises with infarction of the visual cortex or its afferent fibers is patient competency to drive a vehicle. Patients with infarction in the territory of the left PCA may have preserved macular vision but severe restriction of peripheral vision, as well as an inability to read in any visual field. Patients with infarction in the territory of the right PCA may have significant visual hemineglect.

Careful examination of the patient and knowledge of local laws governing the right to drive are a necessity. Repeated visual-field testing is required (some recovery of vision may occur), as well as further assessment by occupational therapists and clinicians.

Patients often have to relinquish their driver’s license because of the visual field loss. This may result in considerable loss of independence and provoke anger and grief in the patient, for which counseling may be required.

Treatments for recurrent stroke prevention should be instituted as soon as possible. The identified etiology of the stroke will determine what treatments are indicated (medical, surgical, endovascular) for preventing recurrent events.

Anticoagulant and antiplatelet therapies

Long-term anticoagulation with warfarin is indicated in several settings—including atrial fibrillation, selected cases with significant global or regional cardiac hypokinesis (ejection fraction < 35%), patent foramen ovale with documented hypercoagulable condition, and arterial hypercoagulable state—for prevention of recurrent strokes.  Novel anticoaguants, including dabigatran, rivaroxaban and apixaban, may be used for stroke prevention in the context of non-valvular atrial fibrillation.  The risks of recurrent stroke have to be balanced with the risk of oral anticoagulation therapy. For patients in whom no cause for recurrent strokes can be found despite extensive work-up, antiplatelet therapy is generally recommended instead of anticoagulation therapy.

Antiplatelet therapies are often the mainstay of recurrent stroke prevention. In most cases, they can be instituted immediately, and evidence suggests that doing so decreases recurrent events immediately and chronically. Aspirin, 325 mg daily, has been shown to reduce the rate of acute recurrence of stroke (ie, in the first 14 days after first stroke) when administered within 48 hours of the first stroke.

Ticlopidine, clopidogrel, and aspirin plus extended-release dipyridamole (Aggrenox) also prevent recurrent stroke, although ticlopidine is rarely used due to a higher risk of side effects. These agents produce platelet inhibition by a number of different mechanisms.

Early anticoagulation with heparin

Anticoagulation is infrequently indicated in the acute phases of posterior cerebral artery (PCA) stroke. While historically, early anticoagulation (generally with heparin infusion) has been used in acute stroke, significant supporting data have been absent.

Indeed, early anticoagulation, particularly with heparin, has been studied in a number of diagnostic settings but has not been demonstrably proven to be beneficial. Cochrane reviews of studies totaling more than 20,000 patients have suggested that early anticoagulation does not produce a mortality or morbidity benefit.[22, 23] In specific cases (large vessel, high-grade stenosis), some benefit may have been seen; however, this was offset by increased hemorrhagic complications.

The rationale for the acute use of anticoagulant therapy lies in preventing acute recurrence of stroke; however, trials have shown that this risk of early recurrent stroke is low and that heparin does not provide any functional or survival advantage. Nonetheless, this remains a controversial area, with some stroke experts having strong opinions about acute anticoagulation.

In general, the stroke mechanism should be identified so that a better, informed decision can be made before long-term anticoagulation is chosen. PCA strokes that arise from vertebral artery dissection are more frequently treated with anticoagulation, although again there is a paucity of data to support this use.

Early anticoagulation may be the most appropriate preventive strategy in specific circumstances that are considered high-risk, such as the presence of an intracardiac thrombus or a dissection with visualized large intraluminal thrombus. Strokes caused by atrial fibrillation do not require early anticoagulation with heparin. Studies have demonstrated that the risk of recurrent stroke within the first weeks is approximately 1%.[24] Early heparinization in this setting is associated with no clear stroke prevention benefit but is associated with increased hemorrhagic complications.

LMWH

Heparin and low-molecular-weight heparin (LMWH) should be titrated individually based on aPTT. A heparin bolus is infrequently given due to concerns of hemorrhage. This approach may be justifiable given evidence that heparin does not provide an acute advantage in nonselective use in ischemic stroke.

The optimal dosing regimen for heparin in stroke has not been established. LMWHs, also known as fractionated heparins, have become available in the last few years and have revolutionized therapy of venous thrombosis and acute coronary syndromes.

LMWH therapy in the acute setting should be cautiously considered because no antidote is available for quick reversal of anticoagulation in the event of intracerebral hemorrhage. In the subacute setting, LMWH may be used as a bridge to long-term anticoagulation with warfarin.

Other prophylactic measures

Effective treatment of hypertension has been proven to reduce the risk of recurrent stroke. In addition, emphasis should always be placed on smoking cessation, moderation of alcohol use, and discontinuation of illicit substance use.

In patients with elevated cholesterol, sustained reduction in cholesterol levels may also reduce the chances of stroke. Numerous studies have demonstrated a modest stroke risk-reduction benefit in patients with coronary heart disease; however, the results of the Stroke Prevention by Aggressive Reduction in Cholesterol levels (SPARCL) study suggest that patients without CHD also have a lower incidence of stroke on statin therapy.[25]

Numerous statins (eg, lovastatin, simvastatin, pravastatin, atorvastatin) are available. All inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the anabolism of cholesterol. These drugs are effective in reducing levels of low-density lipoprotein (LDL) cholesterol but have less effect on high-density lipoprotein (HDL) cholesterol and triglycerides.

The statins may have other, pleiotropic effects in stroke prevention, such as plaque stabilization, reduction of free radical formation, and anti-inflammatory, immunomodulatory, and antiplatelet effects. Additionally, prestroke use of statins may be associated with smaller infarct or better outcomes. Large vessel atherosclerosis may undergo regression in patients treated with statin therapy.

As previously mentioned, long-term anticoagulation to prevent recurrent strokes is indicated in several settings, including the following:

• Atrial fibrillation

• Selected cases with significant global or regional cardiac hypokinesis (ejection fraction < 35%)

• Patent foramen ovale with documented hypercoagulable condition

• Arterial hypercoagulable state

When no cause for recurrent strokes can be found, antiplatelet therapy—eg, with aspirin, ticlopidine, clopidogrel, or aspirin plus extended-release dipyridamole (Aggrenox)—is generally recommended instead of anticoagulation therapy.

As a result, patients entering the rehabilitation phase of their hospital course may be prescribed an anticoagulant, clopidogrel, or aspirin. The selection of these agents is dependent on the etiology of the posterior cerebral artery (PCA) stroke, associated complications, comorbidities, and prior medical history. These medications are used to prevent further cerebral vascular ischemic events.

Class Summary

These agents inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, a potent platelet activator.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) from binding to the platelet receptor and the subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

Aspirin (Bayer Aspirin, Ascriptin Maximum Strength, Ecotrin, Bufferin)

Aspirin treats mild to moderate pain and headache. It inhibits prostaglandin synthesis, which prevents the formation of platelet-aggregating thromboxane A2.

Ticlopidine

Ticlopidine is second-line antiplatelet therapy for patients in whom aspirin is not tolerated or is ineffective.

Dipyridamole 200 mg/aspirin 25 mg (Aggrenox)

Dipyridamole-aspirin is a combination antiplatelet agent that takes advantage of the additive antiplatelet effects of the 2 drugs. Dipyridamole acts via the adenosine-platelet A2-receptor system, whereas aspirin inhibits platelet aggregation by causing irreversible inhibition of cyclooxygenase system, thereby reducing generation of thromboxane A2, a powerful enhancer of platelet aggregation and vasoconstriction.

Class Summary

Anticoagulants prevent recurrent embolism and the extension of the thrombosis.

Warfarin (Coumadin, Jantoven)

Warfarin interferes with the hepatic synthesis of vitamin K-dependent coagulation factors. It is used for the prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor the dose to maintain an INR in the range of 2-3. Patients with prosthetic cardiac valves may require higher INR levels.

Dabigatran (Pradaxa)

Competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development. Inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Indicated for prevention of stroke and thromboembolism associated with nonvalvular atrial fibrillation.

Rivaroxaban (Xarelto)

Factor Xa inhibitor indicated to reduce risk of stroke and systemic embolism with nonvalvular atrial fibrillation. Dose is adjusted according to estimated creatinine clearance.

Apixaban (Eliquis)

Inhibits platelet activation and fibrin clot formation via direct, selective, and reversible inhibition of free and clot-bound factor Xa. Factor Xa, as part of the prothrombinase complex, catalyzes the conversion of prothrombin to thrombin. Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin.

Class Summary

In patients with elevated cholesterol, sustained reduction in cholesterol levels may also reduce the chances of stroke. These agents lower LDL-C levels by reducing the production of mevalonic acid from HMG-CoA and by stimulating LDL catabolism. They also lower triglyceride levels and raise serum HDL-C levels, and they have a low incidence of adverse effects, the most common being hepatotoxicity and myopathy.

Lovastatin (Altoprev, Mevacor)

Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Adjunct to dietary therapy in reducing serum cholesterol. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.

Simvastatin (Zocor)

Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. In addition, agents in this class possess pleitropic properties including improved endothelial function and reduced inflammation at the site of the coronary plaque. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.

Pravastatin (Pravachol)

Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Agents in this class also inhibit platelet aggregation and have anticoagulant effects. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.

Atorvastatin (Lipitor)

Competitively inhibits HMG-CoA, which catalyzes rate-limiting step in cholesterol synthesis. Agents in this class also decrease levels of high-sensitivity C-reactive protein, which is a protein associated with inflammatory responses. Before initiating therapy, place patients on cholesterol-lowering diet for 3-6 mo, and continue diet indefinitely.