What it is:Sudden focal neurologic dysfunction from an interruption in blood supply to the brain, spinal cord, or retina, lasting at least 24 hours (a TIA is the same picture but resolves in under 24 hours, usually under 30 minutes). 87% of strokes are ischemic(a vessel gets blocked), 13% are hemorrhagic(a vessel bleeds). Same organ, opposite mechanism, opposite emergency treatment.
The core problem:In ischemic stroke, brain tissue starts dying within minutes of losing blood flow, but there's a ring of tissue around the core, the penumbra, that's struggling but still alive. You have a few hours to save it before it's gone for good. In hemorrhagic stroke, the problem isn't too little blood, it's blood in the wrong place compressing and poisoning the tissue around it.
What you do about it:Get a CT scan immediately to sort ischemic from hemorrhagic, because the treatments are near-opposite (you clot-bust one and you correct coagulopathy in the other). Then it's a race against the clock for reperfusion in ischemic stroke, or a race to stop expansion in hemorrhagic stroke. Once the acute phase passes, the whole game shifts to secondary prevention: antiplatelet or anticoagulant, statin, and BP control, for the rest of the patient's life.
Think of stroke pharmacotherapy as three completely separate clocks running at once. Clock 1 (minutes to hours):is this patient a thrombolysis or thrombectomy candidate right now. Clock 2 (the first 48–72 hours):permissive hypertension, temperature control, glucose control, avoid piling complications onto an already injured brain. Clock 3 (after the first week, forever):secondary prevention decisions that will follow this patient for the rest of their life. Almost every test question is really asking which clock you're on.
Before anything else, figure out which kind of stroke you're dealing with. Giving a clot-buster to a bleeding brain is catastrophic, and this single fork in the road determines almost the entire treatment pathway.
| Ischemic stroke | Hemorrhagic stroke | |
|---|---|---|
| Frequency | 87% | 13% |
| Mechanism | Vessel occluded by local thrombus or embolus, cutting off flow | Vessel ruptures, blood collects in or around brain tissue |
| Pain | Usually not painful; some report headache | Headache more common and more severe |
| Subtypes | Large-artery atherosclerosis, small-vessel disease, cardioembolic (~25%, think AFib), cryptogenic | Intracerebral hemorrhage (ICH, bleeding into parenchyma) and subarachnoid hemorrhage (SAH, usually aneurysm or AVM rupture) |
| Acute drug therapy | Thrombolysis, antiplatelet | Anticoagulant reversal if applicable, aggressive BP control |
A TIA is not a "mini stroke" you can shrug off.It's a medical emergency and the single biggest warning sign you'll ever get, because stroke risk after a TIA is highest in the first few days. TIA and ischemic stroke share a pathophysiology and a workup; the only difference is whether the tissue actually infarcted or the vessel reopened before permanent damage set in.
An artery occludes, from local atherosclerotic thrombus or from an embolus that traveled from somewhere else (most often the heart in a patient with AFib, valvular disease, or another prothrombotic cardiac problem, accounting for roughly 25% of ischemic strokes). Blood flow drops, and the tissue directly downstream starts to die. Around that dead core sits the ischemic penumbra, tissue that's ischemic but still has intact membranes. It's alive, but it's on borrowed time, and it is the only part of the brain your interventions can actually save.
Inside ischemic tissue, oxygen deprivation halts oxidative phosphorylation and forces anaerobic metabolism. ATP runs out. Without ATP, ion pumps fail, so sodium, water, and lactate pile up inside the cell, causing cytotoxic edema. Calcium floods in and activates lipases and proteases that chew up membranes and proteins. Excitatory amino acids like glutamate and aspartate get released and spread the damage to neighboring cells, generating free radicals, prostaglandins, and leukotrienes along the way. This entire cascade unfolds over just 2–3 hoursfrom the onset of ischemia, and it ends in apoptosis and necrosis. That short window is exactly why "time is brain" isn't a slogan, it's the pharmacology.
Every acute ischemic stroke intervention (alteplase, tenecteplase, thrombectomy) exists to reopen the vessel before the penumbra finishes dying. Every secondary prevention drug (antiplatelet, anticoagulant, statin, antihypertensive) exists to stop the next clot from forming in the first place. That's the entire chapter in two sentences.
Modifiable risk factorsfor ischemic stroke: hypertension, cigarette smoking, diabetes, atrial fibrillation, and dyslipidemia. Every one of those is also a treatable secondary prevention target, which is not a coincidence.
Subarachnoid hemorrhage (SAH) results from trauma or from a ruptured intracranial aneurysm or arteriovenous malformation (AVM). Intracerebral hemorrhage (ICH) happens when bleeding into the brain parenchyma itself forms a hematoma. The hematoma physically compresses surrounding tissue, and early hematoma expansion within the first 3 hoursis common and drives worse outcomes and higher mortality, which is exactly why acute BP control matters so much here. On top of the mechanical injury, a second wave of damage follows from the inflammatory response, cerebral edema, and toxicity from blood breakdown products.
Patients may not be able to give you a reliable history themselves because the deficit itself impairs cognition or language, so get the story from whoever witnessed it. Common complaints: sudden unilateral weakness, inability to speak, vision loss, vertigo, or a fall. Ischemic stroke usually isn't painful; hemorrhagic stroke more often presents with severe headache.
| Circulation involved | Typical findings |
|---|---|
| Anterior circulation | Aphasia is common; hemi- or monoparesis; hemisensory deficits; visual field defects; dysarthria; altered consciousness |
| Posterior circulation | Vertigo and diplopia |
Sudden weakness or numbness (especially one-sided), sudden trouble speaking or understanding speech, sudden vision loss, sudden severe headache with no known cause, and sudden dizziness, loss of balance, or falling. This is the "BE-FAST" territory your objectives file is pointing at: Balance, Eyes, Face, Arm, Speech, Time. Time is the one that separates stroke education from every other neuro topic, because it's the only diagnosis on the differential where minutes change the treatment plan.
The diagnostic priority in suspected acute stroke is speed: get imaging fast enough to still act on it.
They aren't ordered to diagnose the stroke, they're ordered because hypoglycemia can mimic a stroke (and you don't want to thrombolyse a sugar problem), and because a low platelet count or deranged coagulation is an exclusion criterion for alteplase. Every lab in this list earns its place by gating a treatment decision, not by describing the disease.
Reduce mortality and long-term disability through reperfusion or bleed control
Immobility breeds VTE, infection, and pressure injury
The lifelong secondary prevention plan starts here
The instinct is to treat high blood pressure aggressively. In acute ischemic stroke, that instinct is usually wrong. Permissive hypertension, letting BP run as high as 220/120 mm Hgfor the first 48–72 hours, is standard for patients who aren't candidates for thrombolysis or thrombectomy and don't have another comorbidity forcing BP control, because early aggressive lowering does not improve survival and can worsen perfusion to the penumbra. If a comorbid condition does require lowering, a modest 15% reduction is reasonable.
Everything flips if the patient is eligible for alteplase or mechanical thrombectomy. Then BP must be brought below 185/110 mm Hg before treatment, because uncontrolled hypertension during thrombolysis is a bleeding risk. Use short-acting, easily titratable IV agents: labetalol 10–20 mg IV over 1–2 minutes(may repeat), nicardipine 5 mg/h IVtitrated up by 2.5 mg/h every 5–15 minutes to a max of 15 mg/h, or clevidipine 1–2 mg/h IV, doubling the dose every 2–5 minutes to a max of 21 mg/h. Hydralazine, enalaprilat, and nitroprusside infusions are other options.
Ischemic without lysis candidacy:permissive up to 220/120. Ischemic, lysis-eligible:get below 185/110 first. Hemorrhagic with SBP >220:aggressive continuous-infusion lowering, target SBP 140 is considered safe and may help functional outcomes. SAH pre-aneurysm-repair:SBP <160. Three different numbers for three different situations, all testable against each other.
Fever worsens outcomes in both ischemic and hemorrhagic stroke, so find the source and treat it, pharmacologically or otherwise, to keep the patient normothermic. Induced hypothermia is not standard practice outside of clinical trials, the evidence isn't there yet.
Mechanical thrombectomy is strongly recommended for anterior circulation occlusions in the internal carotid artery or the M1 segment of the middle cerebral artery, when performed within 6 hoursof onset, and may be considered in select patients out to 6–24 hours. Its benefit in posterior circulation occlusion is less established and gets decided case by case. Decompressive hemicraniectomy can relieve dangerous intracranial pressure from cerebral edema and improve survival and function in select patients. None of this replaces coordinated multidisciplinary care and early rehabilitation, which reduces overall disability across the board.
This is the highest-yield pharmacology in the chapter. Reperfusion therapy only works if you thread a narrow needle: right diagnosis, right window, right patient, right protocol.
(1) Activate the stroke team. (2) CT scan to rule out hemorrhage. (3) Treat as early as possible, within 4.5 hoursof symptom onset. (4) Confirm every inclusion criterion is met and no contraindication is present. (5) Give alteplase 0.9 mg/kg IV, max 90 mg total, with 10% as a bolus over 1 minuteand the remaining 90% infused over 1 hour. (6) Hold anticoagulants and antiplatelets for 24 hoursafter alteplase. (7) Watch closely for BP spikes, neuro status changes, and bleeding.
| Recommendation | Evidence grade |
|---|---|
| Alteplase 0.9 mg/kg IV (max 90 mg), within 3 hours of onset | Class I, Level A |
| Same alteplase regimen, between 3 and 4.5 hours of onset | Class I, Level B-R |
| Tenecteplase 0.25 mg/kg IV bolus (max 25 mg) as an alternative in patients eligible for mechanical thrombectomy | Class IIb, Level B-R |
| Aspirin 160–325 mg daily, started within 48 hours of onset | Class I, Level A |
Inclusion:age ≥18, clinical diagnosis of ischemic stroke with a neurologic deficit, and symptom onset well-established to be under 4.5 hours before treatment starts.
Absolute contraindications:history of intracerebral hemorrhage, ischemic stroke within the prior 3 months, symptoms or imaging consistent with SAH or acute ICH, current use of a direct thrombin inhibitor or factor Xa inhibitor within the prior 48 hours, treatment-dose LMWH within the prior 24 hours, infective endocarditis, intra-axial intracranial neoplasm, aortic arch dissection, active internal bleeding or coagulopathy (platelets <100,000/mm³, INR >1.7, aPTT >40 sec, PT >15 sec), severe head trauma in the prior 3 months, and GI malignancy or bleeding within the prior 21 days.
Use clinical judgment for:an unruptured or unsecured AVM or aneurysm >10 mm, major surgery or nonhead trauma, a history of bleeding diathesis, and extensive hypoattenuation already visible on the initial CT.
Tenecteplase is a single IV bolus, no infusion pump, no hour-long monitoring of an ongoing drip. That logistical simplicity is why it's gaining traction as an alteplase alternative, particularly for patients heading straight to mechanical thrombectomy. Its evidence grade (IIb, B-R) is weaker than alteplase's, so it's "reasonable," not yet the default.
Once thrombolysis and thrombectomy are off the table, do not reach for heparin. Therapeutic anticoagulation is not routinely recommendedin the early phase of acute ischemic stroke. If anticoagulation is needed for an unrelated reason like VTE prophylaxis, weigh that need against the real risk of turning an ischemic stroke hemorrhagic.
Once the acute phase passes (roughly the first week), the entire focus shifts to stopping the next event. Every ischemic stroke or TIA patient needs long-term antithrombotic therapy, and the drug class depends entirely on the mechanism: antiplatelet for noncardioembolic, anticoagulant for cardioembolic.Mixing these up is the single most common secondary-prevention error.
| Regimen | Evidence |
|---|---|
| Aspirin 50–325 mg daily | Class I, Level A |
| Aspirin 25 mg + extended-release dipyridamole 200 mg, twice daily | Class I, Level A |
| Clopidogrel 75 mg daily | Class I, Level A |
Ticagrelor is also recognized as an option. Pick an alternate agent if the patient can't tolerate or is allergic to aspirin. These are interchangeable first-line options, not a sequential ladder, choice comes down to tolerability, cost, and patient-specific factors like GI bleed history.
When the source is atrial fibrillation (the classic cardioembolic setup), oral anticoagulation beats antiplatelet therapy outright, aspirin with or without clopidogrel is no longer recommended for AFib-driven stroke prevention because it isn't effective enough to justify the added bleeding risk. The CHA₂DS₂-VASc scoreis what quantifies that risk and drives the anticoagulate-or-not decision.
| Risk factor | Points |
|---|---|
| Congestive heart failure | 1 |
| Hypertension | 1 |
| Age ≥75 years | 2 |
| Diabetes | 1 |
| Stroke / TIA / systemic embolus history | 2 |
| Vascular disease (PAD, prior MI, aortic plaque) | 1 |
| Age 65–74 years | 1 |
| Sex category (female) | 1 |
That's the pointed irony of this score in a stroke chapter: having had the very event you're trying to prevent is itself the second-highest-weighted risk factor for having another one. Age points are notcumulative, a patient can't score both the 65–74 point and the ≥75 points, max age contribution is 2.
Interpreting the score:0 in males (or a lone sex point in females) means no anticoagulation. A score of 1 in males or 2 in females (driven by female sex plus one more factor) means anticoagulation is reasonable, DOAC preferred over warfarin. A score of ≥2 in males or ≥3 in females means anticoagulation is recommended, again DOAC preferred, or warfarin with an INR goal of 2–3 if a DOAC isn't appropriate.
All four DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) outperformed or matched warfarin for stroke prevention in their respective pivotal trials (ARISTOTLE, ROCKET-AF, RE-LY, ENGAGE AF-TIMI), and all four showed lower rates of hemorrhagic stroke than warfarin specifically, which matters a lot in a chapter about preventing strokes, not causing a different kind. But renal function is what usually breaks the tie:
Warfarin still has a role: mechanical heart valves are a hard DOAC contraindication (increased thromboembolic events were seen with both dabigatran and apixaban in dedicated valve trials), and warfarin remains preferred with significant hepatic disease or when cost and INR-monitoring access make more sense than DOAC cost.
Notice ACEi/ARB shows up twice in this chapter with two different jobs: as a mortality-reducing GDMT drug in heart failure, and here as a stroke-recurrence-reducing antihypertensive. Same drug class, same underlying logic (control the pressure that damages vessels and organs over time), different disease being prevented.
| Acute thrombolysis | ||
| Alteplase | 0.9 mg/kg IV, max 90 mg. 10% as bolus over 1 min, remainder over 1 hr. Within 4.5 hr of onset. | |
| Tenecteplase | 0.25 mg/kg IV bolus, max 25 mg. Alternative if bound for thrombectomy. | |
| Aspirin (post-lysis) | 160–325 mg daily, started 24–48 hr after onset, and ≥24 hr after alteplase | |
| Acute IV antihypertensives (only if lysis-eligible or hemorrhagic) | ||
| Labetalol | 10–20 mg IV over 1–2 min, may repeat | |
| Nicardipine | 5 mg/h IV, titrate up by 2.5 mg/h q5–15 min, max 15 mg/h | |
| Clevidipine | 1–2 mg/h IV, double the dose q2–5 min, max 21 mg/h | |
| Secondary prevention - antiplatelet (noncardioembolic) | ||
| Aspirin | 50–325 mg daily | |
| Aspirin/ER-dipyridamole | 25 mg / 200 mg twice daily | |
| Clopidogrel | 75 mg daily | |
| Secondary prevention - anticoagulation (cardioembolic / AFib) | ||
| Warfarin | Dose to target INR 2–3 | |
| Apixaban | 5 mg BID | 2.5 mg BID if ≥2 of: age ≥80, weight ≤60 kg, SCr ≥1.5 mg/dL |
| Dabigatran | 150 mg BID | 75 mg BID if CrCl 15–30 (PK data only) |
| Edoxaban | 60 mg daily | 30 mg daily if CrCl 15–50; avoid if CrCl >95 (AFib) |
| Rivaroxaban | 20 mg daily | 15 mg daily if CrCl 15–50 (AFib) |
| Lipid management | ||
| Atorvastatin (LDL >100, no CHD) | 80 mg daily | |
| High-intensity statin (ASCVD) | Goal LDL <70 mg/dL; add ezetimibe if needed; PCSK9i if still ≥70 | |
Pharmacologic options are limited in spontaneous ICH, most of the "treatment" is BP control, surgical evaluation, and reversing whatever put the patient at risk of bleeding in the first place.
When ICH happens in a patient on an anticoagulant, reverse it. This is one of the few true pharmacologic emergencies in this chapter.
| Drug | First-line reversal | Alternate |
|---|---|---|
| Warfarin | Vitamin K 10 mg IV x1 and4-factor PCC (INR 2–<4: 25 units/kg, max 2500 units · INR 4–6: 35 units/kg, max 3500 units · INR >6: 50 units/kg, max 5000 units) | Vitamin K 10 mg IV x1 and FFP 10–15 mL/kg |
| Dabigatran | Idarucizumab 5 g IV x1 | Hemodialysis, or 4PCC 50 units/kg |
| Rivaroxaban ≤10 mg | Andexanet alfa 400 mg IV bolus (30 mg/min), then 4 mg/min infusion up to 120 min | 4PCC 50 units/kg |
| Rivaroxaban >10 mg / unknown | <8 hr or unknown timing: andexanet 800 mg bolus then 8 mg/min infusion · ≥8 hr: 400 mg bolus then 4 mg/min infusion | 4PCC 50 units/kg |
| Apixaban ≤5 mg | Andexanet alfa 400 mg IV bolus (30 mg/min), then 4 mg/min infusion up to 120 min | 4PCC 50 units/kg |
| Apixaban >5 mg / unknown | <8 hr or unknown timing: andexanet 800 mg bolus then 8 mg/min infusion · ≥8 hr: 400 mg bolus then 4 mg/min infusion | 4PCC 50 units/kg |
| Edoxaban | Andexanet alfa not studied for this agent | 4PCC 50 units/kg |
Every factor Xa inhibitor (rivaroxaban, apixaban, edoxaban) leans on andexanet alfaas first-line, with 4-factor PCCas the fallback everywhere andexanet isn't available or studied. Dabigatran is the outlier because it has its own dedicated, fast, complete reversal agent in idarucizumab. Warfarin is the only one that needs both a fast-acting factor product (4PCC) and a slower long-term correction (vitamin K), because 4PCC alone wears off before warfarin's effect does.
| Parameter | When | Watching for |
|---|---|---|
| Neuro exam + BP, post-alteplase | Every 15 min x1 hr, then every 30 min x6 hr, then every hour x17 hr, then every shift | Symptomatic intracranial hemorrhage, the feared complication of thrombolysis |
| Bleeding, all antithrombotics | Daily (aspirin, clopidogrel, dipyridamole/aspirin, warfarin, DOACs) | GI bleed, bruising, hematuria, any occult blood loss |
| PT/INR + H&H, warfarin | Daily while inpatient, then per outpatient monitoring schedule | Time in therapeutic range; anemia from occult bleeding |
| Neurologic status, general | Intensively throughout acute admission | Recurrence or extension of the stroke |
| Temperature | Continuously in acute phase | Fever, which independently worsens outcomes |
| Renal function | Baseline and periodically on any DOAC | Need for dose adjustment; renal function changes over time even if it's normal at baseline |
| LDL | After statin initiation/titration | Goal <70 (ASCVD) or <100 (no known CHD) |
| Blood pressure, long-term | Every visit | Goal <130/80 for secondary prevention |
Extension of the original lesion, cerebral edema with rising intracranial pressure, hypertensive emergency, infection (urinary or respiratory are the usual suspects), venous thromboembolism, electrolyte abnormalities or rhythm disturbances, and recurrent stroke. When a stabilized stroke patient decompensates, run through this list before assuming it's "just the stroke."