Part VII
Acute Management
How a 21st-century stroke service turns the four-and-a-half-hour countdown into a mechanised, time-stamped, neuron-saving sequence: thrombolysis, thrombectomy, blood pressure control, neurocritical care, and the reversal pharmacology that surrounds them all.
1. The Acute Stroke Protocol
The modern stroke code is an industrial workflow. Every minute is measured, every station is pre-staged, and the patient is the only thing that moves. The system is audited against two flagship benchmarks — the door-to-needle time for IV thrombolysis and the door-to-puncture time for endovascular thrombectomy. Both are pure organisational outputs, completely independent of biology, and both correlate linearly with disability-free survival.
IV Thrombolysis
Door-to-needle ≤ 45 min
Target Stroke Phase III aspirational goal: ≤ 30 min in 50% of patients, ≤ 45 min in 75%. Each 15-minute reduction yields ~4% absolute increase in disability-free outcome (Saver et al., JAMA 2013).
Endovascular Thrombectomy
Door-to-puncture ≤ 90 min
AHA/ASA target for direct arrivals; ≤ 60 min for “drip-and-ship” transfers. Every 30-minute delay reduces probability of functional independence (mRS 0–2) by ~10% (Saver et al., JAMA 2016).
The protocol begins before the patient arrives. EMS pre-notification activates a parallel-processing cascade so the CT scanner, neurologist, pharmacy, and angiography suite are ready on arrival.
- t = 0
Pre-arrival
EMS pre-notification with last-known-well time, NIHSS, antithrombotic history. Lab draws (POC glucose, INR) en route.
- t + 5
Door
Direct-to-CT triage. ED physician + stroke neurologist + nurse + pharmacist meet the stretcher in the scanner.
- t + 10
CT initiated
Non-contrast CT to exclude haemorrhage; CT angiography head-and-neck; if > 4.5 h or unknown onset, CT perfusion.
- t + 20
Decision point
NCCT clear of blood and large hypodensity; ASPECTS ≥ 6; LVO identified on CTA → dual-track lysis + thrombectomy.
- t + 25
Tenecteplase / alteplase
Bolus given in the scanner or at bedside. Do not wait for transfer to administer.
- t + 60
Groin puncture
For LVO, transport to angio suite while lytic infuses. Stent retriever or aspiration first pass.
- t + 90
Recanalisation
TICI 2b/3 reperfusion is the procedural goal; achieved in > 80% with modern devices.
Cross-link: the imaging triage that makes this possible is detailed in Part VI — Imaging & Diagnosis.
2. IV Thrombolysis: Alteplase (rt-PA)
Alteplase is recombinant human tissue plasminogen activator: a single-chain 527-residue serine protease that converts fibrin-bound plasminogen to plasmin, enzymatically cleaving the fibrin meshwork of a fresh thrombus. Its breakthrough — relative to the systemic fibrinolytics of the 1980s (streptokinase, urokinase) — is fibrin-specificity: tPA’s catalytic efficiency for plasminogen rises ~100-fold when both bind a common fibrin scaffold, concentrating activity at the clot rather than throughout circulating blood.
Tissue plasminogen activator (1A5H)
Catalytic domain of human tPA. The active-site triad (His322, Asp371, Ser478) cleaves the Arg561–Val562 bond of plasminogen to liberate plasmin. Alteplase is the recombinant full-length protein.
Dose
0.9 mg/kg IV (maximum 90 mg total), given as 10% bolus over 1 minute, then 90% as infusion over 60 minutes.
Dose calculation: \( D_{\text{total}} = \min(0.9 \cdot \text{wt}_{\text{kg}},\ 90)\ \text{mg} \), \( D_{\text{bolus}} = 0.1 \cdot D_{\text{total}} \), \( \dot{D}_{\text{inf}} = \frac{0.9 \cdot D_{\text{total}}}{60\ \text{min}} \).
The trial cascade
- NINDS rt-PA Stroke Study (NEJM 1995) — randomised 624 patients within 3 h of onset to alteplase vs placebo. Absolute increase in mRS 0–1 outcome of ~13% (39% vs 26%); symptomatic ICH rose from 0.6% to 6.4% but 90-day mortality was unchanged. The trial that founded the modern field.
- ECASS-3 (NEJM 2008) — extended the window to 4.5 h: 821 patients, mRS 0–1 at 90 days 52.4% vs 45.2% (NNT ~14), sICH 2.4% vs 0.2%.
- IST-3 (Lancet 2012) — supported benefit in older patients (>80 years) and within 6 h on a shift analysis.
- WAKE-UP (NEJM 2018) — in wake-up strokes with DWI/FLAIR mismatch, alteplase improved mRS 0–1 (53.3% vs 41.8%).
- EXTEND (NEJM 2019) — perfusion mismatch up to 9 h: alteplase improved mRS 0–1 (35.4% vs 29.5%).
The pooled meta-analysis (Emberson et al., Lancet 2014, n = 6756 across 9 trials) confirms a clear time-dependent benefit: \( \mathrm{OR}(\text{mRS 0–1}) = 1.75\) at 0–3 h, \(1.26\) at 3–4.5 h, \(\sim 1.0\) thereafter.
3. IV Thrombolysis: Tenecteplase
Tenecteplase (TNK-tPA) is a triple-substituted variant of alteplase: T103N adds an N-glycosylation site to extend half-life, N117Q removes one to suppress hepatic clearance, and KHRR(296–299)AAAA confers resistance to plasminogen activator inhibitor-1 (PAI-1). The pharmacological consequences are profound:
~17 min
half-life (vs ~5 min for tPA)
~14×
fibrin specificity vs alteplase
~80×
resistance to PAI-1
Dose
The trial portfolio
- EXTEND-IA TNK (NEJM 2018) — in 202 LVO patients, TNK 0.25 mg/kg before thrombectomy achieved early reperfusion in 22% vs 10% with alteplase (substantial reperfusion at first angiogram).
- NOR-TEST (Lancet Neurol 2017) — non-inferiority for mild-to-moderate stroke at higher dose (0.4 mg/kg).
- AcT (Lancet 2022) — 1577 Canadian patients, TNK 0.25 mg/kg non-inferior to alteplase for mRS 0–1 at 90 days; sICH equivalent.
- TRACE-2 (Lancet 2023) — 1430 Chinese patients, TNK non-inferior to alteplase.
- TIMELESS (NEJM 2024) — TNK in 4.5–24 h window with perfusion mismatch did not improve mRS overall, though trended better in untreated LVO.
By 2024 most large North American, Australian, and European stroke centres have adopted tenecteplase as the default lytic. The pharmacology is genuinely better; the workflow advantage is decisive.
4. Thrombolysis Contraindications
Lysis is the most powerful and the most dangerous drug in stroke care. The symptomatic intracranial haemorrhage rate is 2–6%, with case-fatality of ~50% when sICH does occur. Contraindications attempt to identify patients where the haemorrhage risk overwhelms expected reperfusion benefit.
| Domain | Absolute / strong relative contraindication |
|---|---|
| Imaging | Any intracranial haemorrhage on CT/MRI; extensive early ischaemic change (ASPECTS < 6 in some protocols). |
| Blood pressure | Sustained BP > 185/110 mmHg despite IV agents (labetalol, nicardipine, clevidipine). |
| Coagulation | INR > 1.7; aPTT prolonged; platelets < 100×109/L. |
| Anticoagulants | Therapeutic LMWH within 24 h; DOAC (apixaban, rivaroxaban, dabigatran, edoxaban) within 48 h (or normal anti-Xa / dilute thrombin time). |
| Glucose | < 50 mg/dL or > 400 mg/dL (relative; correct and re-evaluate). |
| Bleeding | Active internal haemorrhage; recent GI/GU bleed; known bleeding diathesis. |
| Trauma / surgery | Major surgery in the previous 14 days; serious head trauma in 3 months; arterial puncture at non-compressible site < 7 days. |
| Prior intracranial | Known intracranial neoplasm (intra-axial), AVM, aneurysm; prior ICH. |
| Endocarditis | Suspected infective endocarditis — markedly elevated mycotic-aneurysm rupture risk. |
| Aortic dissection | Suspected acute aortic dissection. |
No longer contraindications (per 2019/2021 AHA/ASA): age > 80; NIHSS > 25; pregnancy; menstruation; diabetic retinopathy; dual antiplatelet therapy; recent (non-bleeding) MI; lumbar puncture in past week; early ischaemic changes (ASPECTS ≥ 6).
5. Mechanical Thrombectomy — The 2015 Revolution
No therapy in modern neurology has produced effect sizes as large or as quickly replicated as endovascular thrombectomy (EVT) for proximal large-vessel occlusion. For 20 years (1995–2015), IV alteplase was the only proven reperfusion therapy and its NNT for one mRS reduction was ~7. Then, in a six-month window in 2015, five randomised trials simultaneously reported that adding stent-retriever thrombectomy roughly halved disability:
NEJM 2015
MR CLEAN (Netherlands)
500 patients, < 6 h. mRS 0–2 32.6% vs 19.1%; OR 1.67. The trial that broke the dam.
NEJM 2015
ESCAPE (Canada)
316 patients, < 12 h with collaterals. mRS 0–2 53% vs 29%; stopped early for efficacy.
NEJM 2015
EXTEND-IA (Australia)
70 patients with perfusion mismatch. mRS 0–2 71% vs 40%; reperfusion 100% vs 37%.
NEJM 2015
SWIFT-PRIME (USA)
196 patients, < 6 h. mRS 0–2 60% vs 35%; stopped early.
NEJM 2015
REVASCAT (Spain)
206 patients, < 8 h. mRS 0–2 43.7% vs 28.2%; stopped early after MR CLEAN reported.
HERMES Collaboration meta-analysis — Lancet 2016
NNT ≈ 2.6 for one mRS-point reduction
Pooled individual-patient data from the five trials (n = 1287) gave a common-odds ratio of \(\mathrm{cOR} = 2.49\ (95\%\ \mathrm{CI}\ 1.76\text{–}3.53)\) for improved mRS distribution. The NNT to reduce disability by one point on the modified Rankin Scale is ~2.6; the NNT to achieve functional independence (mRS 0–2) is ~5.
For comparison: NNT for streptokinase in STEMI is ~50, for stenting an unstable coronary lesion ~30, for statins in primary prevention ~100. Thrombectomy for LVO stroke is among the most effective interventions in medicine.
Devices
Two technical paradigms dominate, often combined:
Stent retrievers
Self-expanding nitinol mesh (Solitaire FR, Trevo XP) deployed across the thrombus, allowed to integrate, then withdrawn under proximal aspiration. The first-line device in the 2015 trials.
Aspiration catheters (ADAPT)
Large-bore intermediate catheters (Penumbra ACE, Sofia, React) advanced to the thrombus face and aspirated. COMPASS and ASTER trials show non-inferiority to stent-retrievers as first pass.
Combined techniques (Solumbra, ASAP, BADDASS) achieve TICI 2b/3 rates > 90% with mean number of passes ~1.5. First-pass effect — complete reperfusion on a single attempt — is associated with the best functional outcomes and is now a procedural target.
Eligibility criteria (per AHA/ASA 2019): proximal occlusion (ICA, M1, occasionally proximal M2), pre-stroke mRS 0–1, NIHSS ≥ 6, ASPECTS ≥ 6, time from last known well < 6 h (or up to 24 h with imaging selection — see next section). Cross-link to the reperfusion biology in Part III — Ischaemic Pathophysiology.
6. Late-Window Thrombectomy: DAWN & DEFUSE-3
The 2015 trials all enrolled within 6 h of last-known-well. The 2018 leap was to recognise that biological time is not chronological time: a patient with abundant collaterals can preserve penumbra for many hours longer than the average. Two seminal trials abandoned the clock and used imaging to select.
NEJM January 2018
DAWN — Diffusion-weighted imaging or perfusion-CT Assessment Within 24 h
- Window: 6–24 h from last-known-well.
- Selection: clinical-core mismatch — deficit (NIHSS) too large for the small infarct core on CT-perfusion or DWI.
- Result: 206 patients; mRS 0–2 at 90 days 49% vs 13% (control).
- NNT ≈ 2.8 for functional independence — among the largest effect sizes ever reported in stroke neurology.
- Trial stopped early at first interim analysis for overwhelming efficacy.
NEJM February 2018
DEFUSE-3 — Endovascular Therapy Following Imaging Evaluation
- Window: 6–16 h from last-known-well.
- Selection: CT-perfusion or PWI/DWI perfusion mismatch: ischaemic core < 70 mL, mismatch volume ≥ 15 mL, mismatch ratio ≥ 1.8.
- Result: 182 patients; mRS 0–2 45% vs 17%.
- NNT for functional independence ~3.6.
- Stopped early after DAWN reported.
The conceptual revolution: a patient may present at 18 hours with a large clinical deficit but a tiny core because their collateral circulation has held the penumbra alive. That tissue is still salvageable. Imaging — not the wall clock — identifies who benefits.
Mismatch arithmetic
Penumbra volume on CTP: \( V_{\text{penumbra}} = V_{T_{\max} > 6\text{s}} - V_{\text{core}} \), where \( V_{\text{core}} = V_{\text{CBF} < 30\%\,\text{contralateral}} \).
Mismatch ratio: \( R = V_{T_{\max}>6\text{s}} / V_{\text{core}} \). Eligibility: \( V_{\text{core}} < 70\ \text{mL},\ V_{\text{penumbra}} \geq 15\ \text{mL},\ R \geq 1.8 \).
The whole concept inverts the “time is brain” framing of Part I: time is brain only because the penumbra fails over time. Image the penumbra directly and you image the actual therapeutic window.
Both DAWN and DEFUSE-3 received Class I recommendations from AHA/ASA in 2018, and redrew stroke transfer maps overnight: any patient within 24 hours of LKW with a proximal LVO and a small core is now a candidate for transfer to a thrombectomy centre. The dominant rate-limiting step is no longer biology — it is logistics.
7. Tandem Occlusions & Intracranial Atherosclerotic Disease
Roughly 15% of acute LVO presentations involve a tandem lesion: a proximal cervical internal carotid artery (ICA) occlusion or critical stenosis (typically atherosclerotic) plus a distal intracranial embolus (M1 or M2). The interventionalist must traverse the proximal lesion to reach the intracranial clot, raising decision-points unique to this subset:
- Order of treatment — distal-first (clear the brain first) vs proximal-first (open the conduit). Distal-first is favoured by many groups because intracranial reperfusion is the disability-altering step; cervical access is then re-established with angioplasty ± stent.
- Acute carotid stenting — requires antiplatelet loading (aspirin + IV cangrelor or oral ticagrelor/clopidogrel), which collides with the haemorrhage risk of recent thrombolysis and a fresh infarct.
- Balloon angioplasty alone — an alternative when antiplatelet loading is unsafe; staged stenting at 1–2 weeks if symptomatic restenosis develops.
- TITAN registry & ETIS — observational data favour acute stenting for cervical ICA occlusion in tandem lesions; RCTs (TITAN, EASI-TOC) are pending.
Intracranial atherosclerotic disease (ICAD) as the underlying cause of the LVO — particularly common in East Asian, Hispanic, and Black populations — tends to re-occlude after first-pass clot extraction. Intra-arterial tirofiban or eptifibatide, intracranial angioplasty, or rescue intracranial stenting may be required. The RESCUE-BT and BAOCHE trials provide partial guidance; this remains one of the open frontiers of acute neurointervention.
8. Posterior-Circulation Thrombectomy
Basilar artery occlusion (BAO) is the deadliest presentation in acute stroke: untreated 90-day mortality approaches 80–90%, and survivors are most often locked-in. For two decades after the 2015 anterior-circulation revolution, BAO remained an evidence gap — the BASICS (NEJM 2021) and BEST (Lancet Neurol 2020) trials were underpowered or compromised by crossover.
NEJM October 2022
ATTENTION (China)
340 BAO patients within 12 h; mRS 0–3 at 90 days 46% vs 23%. 90-day mortality 37% vs 55%. Symptomatic ICH 5% vs 0%. Stopped early.
NEJM October 2022
BAOCHE (China)
217 BAO patients in 6–24 h window; mRS 0–3 46% vs 24%. Mortality 31% vs 42%. Confirmed late-window benefit in the posterior circulation.
BAO presents differently from anterior LVO: prodromal vertebrobasilar TIAs, fluctuating consciousness, oculomotor palsies, quadriparesis, and crossed sensorimotor signs. NIHSS often understates severity (it weights cortical signs). The posterior-circulation ASPECTS (pc-ASPECTS) on CT or DWI is used for core estimation; thalamic, midbrain, and pontine hypodensities all count.
A key point: because untreated BAO is so uniformly catastrophic, the threshold for thrombectomy is lower than for anterior circulation — a small posterior-circulation infarct burden remains an indication for EVT well into the late window when there is residual brainstem/cerebellar penumbra.
9. Blood Pressure Management
Acute stroke decouples cerebral autoregulation: in the ischaemic penumbra, perfusion becomes pressure-passive. The therapeutic window between “too low (extends core)” and “too high (haemorrhage and oedema)” is narrow and depends on the treatment scenario.
| Scenario | BP target | Rationale / trial |
|---|---|---|
| Pre-thrombolysis | < 185/110 mmHg | NINDS criteria; enables IV tPA/TNK administration |
| Post-thrombolysis (24 h) | < 180/105 mmHg | Reduces sICH risk after lysis |
| Ischaemic, no lysis | Permissive ≤ 220/120 | Penumbra is pressure-passive; avoid lowering acutely |
| After successful EVT | SBP 140–160 (BP-TARGET) | Lower target reduces reperfusion injury, oedema, sICH; ENCHANTED-2 trended this way |
| Acute ICH | SBP < 140 (within 1 h) | INTERACT-2 (NEJM 2013); ATACH-2 cautioned about renal events at SBP 110–139 |
| SAH (pre-securing aneurysm) | SBP < 160 | Reduce rebleed risk |
Pharmacology toolbox
First-line agents have rapid onset, short half-life, and titratability: labetalol (10–20 mg IV bolus, then infusion 2–8 mg/min); nicardipine (5 mg/h IV, titrate by 2.5 mg/h every 5–15 min, max 15 mg/h); clevidipine (1–2 mg/h, double q90s to effect, max 21 mg/h). Avoid nitroprusside in the acute phase — cyanide accumulation, ICP rise, cerebral steal.
10. Neurocritical Care
Reperfusion is the headline therapy; the dedicated stroke unit is the less-glamorous-but-equally-important supportive layer. Trialled and meta-analysed repeatedly (Cochrane 2020), stroke-unit care alone reduces death or dependency by ~20%, regardless of lysis or thrombectomy. The components:
Airway & aspiration
Bedside dysphagia screen (Yale, 3-oz water test) before any oral intake. Pneumonia is a leading post-stroke killer; NPO status until cleared.
Glycaemic control
Target 140–180 mg/dL. Hyperglycaemia worsens infarct via lactic acidosis and BBB injury; tight control (SHINE, JAMA 2019) provides no benefit and risks hypoglycaemia.
Temperature
Treat fever > 38°C aggressively (paracetamol, cooling). Hypothermia trials (EuroHYP-1, ICTuS-2) negative; normothermia is the target.
Oxygen / haemodynamics
Maintain SpO2 ≥ 94%; supplemental O2 not routine for non-hypoxic patients (Stroke Oxygen Study 2017).
VTE prophylaxis
Intermittent pneumatic compression from day 1 (CLOTS-3, Lancet 2013). Low-dose LMWH from 24–48 h post-lysis if no haemorrhage.
Early mobilisation
AVERT trial: very-early intensive mobilisation worsened outcomes; out-of-bed activity from 24–48 h, titrated to tolerance.
Malignant MCA syndrome & decompressive hemicraniectomy
In ~10% of MCA-territory infarcts, cytotoxic oedema and mass effect produce midline shift, transtentorial herniation, and death without surgical decompression. Mortality of malignant MCA without surgery ~80%; with hemicraniectomy ~30%.
- DECIMAL, DESTINY, HAMLET pooled (Lancet Neurol 2007) — in patients ≤ 60 with malignant MCA, decompression within 48 h: mRS ≤ 4 at 12 months 75% vs 24%; mortality 22% vs 71%.
- DESTINY-II (NEJM 2014) — extended eligibility to patients aged 61–82: survival without severe disability 38% vs 18%; mortality 33% vs 70%. Most older survivors had mRS 4 (moderate-severe disability) — ethically charged outcome conversation.
Indications: clinical deterioration, infarct > 50% MCA territory, midline shift > 5 mm, age generally ≤ 60 (with case-by-case extension); operate within 48 h for best results. Cerebellar infarcts with mass effect (suboccipital decompression ± EVD) follow a parallel logic with even better outcomes.
11. Reversal of Anticoagulants
Two acute-stroke scenarios force the reversal question: (1) an ischaemic stroke patient on an anticoagulant who needs lysis or thrombectomy, and (2) a haemorrhagic stroke patient on an anticoagulant who must be reversed urgently to limit haematoma growth. The principles intersect but the urgency is highest in ICH, where every hour of delay correlates with haematoma expansion and mortality.
Fibrinogen / fibrin (1FZE)
Human fibrinogen — the substrate of the coagulation cascade, polymerised by thrombin into fibrin meshwork, and dissolved by tPA-activated plasmin. The molecule that thrombolysis attacks.
| Anticoagulant | Reversal | Notes |
|---|---|---|
| Warfarin (VKA) | Vitamin K 10 mg IV + 4-factor PCC (Kcentra) 25–50 IU/kg | PCC restores INR within 30 min; FFP slower, larger volume. |
| Dabigatran | Idarucizumab 5 g IV (two 2.5-g vials) | Humanised mAb fragment, RE-VERSE AD trial; dialysis is alternative. |
| Apixaban / rivaroxaban / edoxaban (FXa-i) | Andexanet alfa, 400–800 mg bolus + 2-h infusion or 4F-PCC 50 IU/kg | ANNEXA-4 / ANNEXA-I; andexanet has prothrombotic concerns; 4F-PCC widely substituted. |
| LMWH (enoxaparin) | Protamine sulfate (partial) | Reverses ~60% of anti-Xa activity. |
| Unfractionated heparin | Protamine sulfate, 1 mg / 100 U heparin in last 2–3 h | Full reversal possible. |
| Antiplatelets (clopidogrel, aspirin) | Platelet transfusion not routinely indicated | PATCH (Lancet 2016) showed harm in spontaneous ICH; reserved for surgical needs. |
| Alteplase / tenecteplase | Cryoprecipitate (10 U) + tranexamic acid 1 g IV | For sICH after thrombolysis; check fibrinogen and replace to > 150 mg/dL. |
The ANNEXA-I trial (NEJM 2024) demonstrated that andexanet alfa reduces haematoma expansion in FXa-inhibitor-associated ICH compared with usual care (mostly 4F-PCC), but at the cost of more thrombotic events — and the trial was halted early for efficacy on the primary haemostatic endpoint without a clear functional-outcome advantage. 4F-PCC remains pragmatic and accessible, especially given andexanet’s cost (US$25,000+ per dose).
12. The Future of Acute Care
The next decade of stroke care will be reorganised by three forces: bringing treatment to the patient, automating triage, and finally cracking the neuroprotection problem.
- Mobile stroke units (MSUs) — ambulances equipped with portable CT, point-of-care labs, and a stroke neurologist via telemedicine. The B_PROUD (JAMA 2021) and BEST-MSU (NEJM 2021) trials showed ~25% absolute increase in good 90-day outcomes vs standard EMS, primarily by cutting onset-to-treatment time by 30–45 min. Cost-effectiveness is the open question for widespread adoption.
- AI-assisted CTA / CTP triage — deep-learning systems (Viz.ai LVO, RapidAI, Aidoc) detect large-vessel occlusion on CTA and segment perfusion mismatch in < 3 minutes. They activate neurointerventionalists and inter-hospital transfers automatically. Effect on door-to-puncture: 20–40 minute reductions in implementing centres.
- Neuroprotection — the century-long failure of single-target neuroprotectants (NXY-059, lubeluzole, citicoline) is being revisited with combination strategies. Nerinetide (PSD-95 inhibitor) showed signal in ESCAPE-NA1 in patients not treated with alteplase; uric acid (URICO-ICTUS subgroups), edaravone (Asia approval), and hypothermia by intra-arterial cold saline are under investigation.
- Drone-delivered tPA — in rural settings, autonomous drones could deliver lytics within minutes of a positive FAST screen by a paramedic, prior to ambulance arrival. Concept-stage with regulatory and safety hurdles, but pilot programmes exist (Sweden, Canada).
- Robotic neurointervention — CorPath GRX and successors enable remote thrombectomy by a single operator across state lines, addressing the geographic shortage of interventionalists. First in-human cases reported 2022–2024.
- Wearable stroke detection — consumer-grade ECG (AF detection by Apple Watch, Fitbit) and emerging EEG/photoplethysmography arrays may shorten the recognition lag for cardioembolic stroke and silent-AF detection — the first link in the chain of survival.
For mechanism-targeted prevention and rehabilitation that follow acute treatment, see Part VIII — Prevention & Rehabilitation. For the underlying pharmacology of thrombolytics and antiplatelets, visit the Pharmacology course.