Landmark and practice-changing clinical trials in Acute Coronary Syndrome (ACS)
Landmark and practice-changing clinical trials in Acute Coronary Syndrome (ACS)
Snapshot — quick summary
- Early antiplatelet trials established aspirin + a P2Y12 inhibitor as the foundation of ACS care (ISIS-2, CURE). New England Journal of Medicine
- More potent P2Y12 agents (prasugrel, ticagrelor) reduced ischemic events vs clopidogrel but increased bleeding in selected patients (TRITON-TIMI-38, PLATO). New England Journal of Medicine+1
- Routine manual thrombus aspiration at primary PCI did not improve hard outcomes and may increase stroke risk — practice moved away from routine thrombectomy (TASTE, TOTAL and related analyses). New England Journal of Medicine+1
Key trials by topic
1) Antiplatelet therapy (aspirin + P2Y12)
- CURE (2001) — clopidogrel + aspirin vs aspirin alone in NSTE-ACS: reduced composite of CV death/MI/stroke; established dual antiplatelet therapy (DAPT) for ACS. New England Journal of Medicine
- TRITON-TIMI 38 (2007) — prasugrel vs clopidogrel in ACS undergoing PCI: prasugrel reduced ischemic events but increased major bleeding (notable excess in prior stroke/TIA and elderly). Useful to guide agent selection. New England Journal of Medicine
- PLATO (2009) — ticagrelor vs clopidogrel in ACS: ticagrelor reduced CV death/MI/stroke versus clopidogrel with an acceptable bleeding profile, leading to broad adoption of ticagrelor for many ACS patients. New England Journal of Medicine
2) Early reperfusion / primary PCI, thrombolysis and adjunctive devices
- ISIS-2 (1988) — established benefit of aspirin (and streptokinase) for MI: landmark early reperfusion/antiplatelet evidence (historical foundation). (Classic landmark; see systematic summaries.) cardiologytrials.org
- TASTE (2014, NEJM) — randomized trial of routine thrombus aspiration before primary PCI vs PCI alone: no reduction in mortality or MI at 30 days / 1 year; routine aspiration not supported. New England Journal of Medicine
- TOTAL (2015 and associated reports) — larger randomized trial — routine aspiration offered no benefit and signaled a possible increase in stroke risk; routine manual thrombectomy fell out of routine use. PMC+1
3) Invasive strategy timing and approach in NSTE-ACS
- FRISC-II / RITA-3 / TIMACS (multiple trials across 1990s–2000s): showed benefit of an early invasive strategy for many higher-risk NSTE-ACS patients (reduced composite ischemic events), shaping the guideline recommendation for risk-stratified early invasive management. (Synthesis available in guideline reviews and trial meta-analyses.) cardiologytrials.org
4) Vascular access, anticoagulation and procedural adjuncts
- RIVAL (radial vs femoral) and other radial-access trials: radial access reduced vascular complications and in some high-volume settings reduced mortality in STEMI; radial is now standard at many centers for primary PCI when operator experienced. (See trial meta-analyses / guideline statements.) cardiologytrials.org
- HORIZONS-AMI / HEAT-PPCI and others: compared bivalirudin vs heparin ± GPI — results varied by trial and era (bleeding vs ischaemia tradeoffs). Local practice individualized by bleeding risk and operator preference. (Summaries in interventional cardiology reviews.) cardiologytrials.org
5) Stent era, DES vs BMS and DAPT duration
- Multiple randomized trials and meta-analyses established drug-eluting stents (DES) as superior to bare-metal stents for restenosis; subsequent trials and registries defined optimal DAPT durations and strategies (shorter DAPT for high bleeding risk, longer DAPT when ischemic risk dominates). Expert DAPT guidance synthesizes this evidence. jmatonline.com+1
6) Secondary prevention—statins and intensive lipid therapy
- PROVE-IT TIMI-22 and similar trials showed early high-intensity statin after ACS reduces recurrent events compared with moderate therapy — established high-intensity statin as standard post-ACS. (See PROVE-IT and guideline syntheses.) cardiologytrials.org
Practical takeaways for clinicians
- DAPT (aspirin + P2Y12 inhibitor) is foundational after ACS; choice (clopidogrel vs prasugrel vs ticagrelor) should consider ischemic vs bleeding risk and patient factors (age, prior stroke, planned CABG). New England Journal of Medicine+2New England Journal of Medicine+2
- Routine manual thrombus aspiration at primary PCI is not recommended (no mortality benefit, possible stroke signal). New England Journal of Medicine+1
- Early invasive strategy benefits many higher-risk NSTE-ACS patients; radial PCI reduces access complications where operators are experienced.
Trials on Acute Coronary Syndrome — 40 Interactive MCQs
Basic Q1
Which landmark trial first established the mortality benefit of early aspirin in suspected myocardial infarction?
ISIS-2 (1988) demonstrated the survival benefit of early aspirin (and streptokinase) in acute MI and is a foundational trial supporting routine aspirin use in MI.
Basic Q2
The CURE trial in NSTE-ACS established which principle?
CURE showed that adding clopidogrel to aspirin in NSTE-ACS reduces the composite of CV death, MI, or stroke—establishing modern dual antiplatelet therapy (DAPT) in ACS.
Basic Q3
Which trial compared prasugrel with clopidogrel in ACS patients planned for PCI?
TRITON-TIMI 38 compared prasugrel vs clopidogrel in ACS patients undergoing PCI and found prasugrel reduced ischemic events but increased major bleeding in certain subgroups.
Basic Q4
Which agent was shown to reduce CV death/MI/stroke vs clopidogrel in the PLATO trial?
PLATO showed ticagrelor reduced the composite of CV death/MI/stroke compared with clopidogrel in ACS patients, influencing guideline recommendations.
Basic Q5
The TASTE and TOTAL trials evaluated routine manual thrombus aspiration before primary PCI. What general conclusion emerged?
TASTE and TOTAL found no mortality benefit with routine thrombectomy and signaled potential harms (e.g., stroke signal in some analyses), so routine aspiration is not recommended.
Basic Q6
Which strategy has been associated with lower vascular complications in many trials of PCI access?
Randomized trials and meta-analyses have shown radial access typically reduces vascular complications and access-site bleeding; it is widely adopted for PCI where operators are experienced.
Basic Q7
Which trial established early high-intensity statin therapy after ACS improves outcomes compared with moderate therapy?
PROVE-IT TIMI-22 showed early intensive statin therapy post-ACS reduced recurrent ischemic events versus moderate therapy, supporting high-intensity statins after ACS.
Basic Q8
Which trial result influenced adoption of DAPT (aspirin + P2Y12 inhibitor) as standard for ACS?
CURE established benefit of clopidogrel added to aspirin in NSTE-ACS, forming the basis for modern DAPT in ACS management.
Basic Q9
Which trial compared radial versus femoral access in acute coronary interventions?
RIVAL and other radial trials evaluated access site—showing radial access reduced vascular complications and in some contexts improved outcomes.
Basic Q10
Which trial demonstrated no mortality benefit with routine manual thrombectomy in primary PCI?
TASTE found no mortality or MI benefit from routine manual thrombus aspiration prior to PCI, influencing practice away from routine thrombectomy.
Basic Q11
Which trial’s findings led to wider adoption of ticagrelor in ACS?
PLATO showed ticagrelor reduced the composite endpoint vs clopidogrel, which led to its adoption in many ACS patients as an alternative to clopidogrel.
Basic Q12
Which trial specifically tested routine thrombectomy and reported a possible increase in stroke in some analyses?
TOTAL was a large randomized trial that showed no ischemic benefit from routine aspiration and observed a signal for increased stroke in some analyses, discouraging routine use.
Basic Q13
Which therapy pair is foundational after ACS based on landmark trials?
Multiple trials (CURE, PLATO, TRITON, etc.) support DAPT (aspirin plus a P2Y12 inhibitor) as standard therapy for most ACS patients.
Basic Q14
Which trial provides evidence to start high-intensity statin therapy early after ACS?
PROVE-IT TIMI-22 established benefit of early intensive statin therapy post-ACS compared to moderate statin therapy, reducing recurrent events.
Basic Q15
Which trial focused on the role of an early invasive strategy in NSTE-ACS?
FRISC-II, RITA-3 and TIMACS (among others) demonstrated benefits of a risk-stratified early invasive strategy for many high-risk NSTE-ACS patients.
Basic Q16
Which trial compared bivalirudin with heparin ± GPI in primary PCI and influenced anticoagulation practice?
HORIZONS-AMI and other studies compared bivalirudin vs heparin ± GPI, showing bleeding reductions in some settings but heterogenous results across eras and trials.
Basic Q17
What general lesson about device-based routine strategies in primary PCI came from recent large randomized trials?
Randomized evidence (e.g., TASTE, TOTAL) shows routine adoption of adjunctive devices requires robust trial evidence because not all interventions improve hard outcomes.
Basic Q18
Which trial series most directly informed modern DAPT choices (agent and duration) after PCI?
A body of randomized trials (CURE, TRITON, PLATO) plus later duration and strategy trials inform agent selection and DAPT duration decisions after ACS and PCI.
Basic Q19
Which outcome did many ACS antiplatelet trials measure as a primary composite?
Most pivotal ACS trials used a composite of cardiovascular death, MI, or stroke as their primary efficacy endpoint to capture overall ischemic benefit.
Basic Q20
Which trial provided strong randomized evidence that routine manual thrombus aspiration does NOT reduce mortality at 30 days?
TASTE (a large randomized trial) found no reduction in mortality or MI with routine thrombus aspiration before PCI at early follow-up.
Advanced Q21
In TRITON-TIMI 38, which subgroup experienced excess harm with prasugrel, prompting caution or contraindication?
TRITON-TIMI 38 showed excess bleeding (and net harm) in patients with prior stroke/TIA with prasugrel; this subgroup is generally contraindicated for prasugrel.
Advanced Q22
Which design feature distinguished PLATO from some earlier P2Y12 trials and likely affected its results?
PLATO enrolled a broad ACS population (both STEMI and NSTE-ACS) and randomized early, which increased generalizability and contributed to robust outcome results for ticagrelor.
Advanced Q23
Which trial used a factorial or multifactorial design to evaluate multiple strategies simultaneously in ACS (name one example)?
While classic ACS trials were largely two-arm, contemporary research increasingly uses multifactorial/platform designs; the key concept is trials may test multiple strategies efficiently.
Advanced Q24
HORIZONS-AMI suggested what trade-off when using bivalirudin in primary PCI?
HORIZONS-AMI showed bivalirudin reduced bleeding vs heparin ± GPI in some contexts but the ischemic outcomes varied across trials and eras, prompting tailored anticoagulation choices.
Advanced Q25
Which trial-level consideration is most important when applying results to practice?
External validity depends on trial population, era (stent type, adjunctive therapy), and methods—these must inform how results are applied to today’s patients.
Advanced Q26
In TOTAL, which safety signal altered clinical enthusiasm for routine aspiration?
TOTAL reported a small but concerning increase in stroke in the aspiration arm in some analyses, which discouraged routine aspiration despite no ischemic benefit.
Advanced Q27
Which ACS trial finding influenced guideline-driven selection against prasugrel in certain patients?
TRITON’s subgroup results led to specific warnings/contraindications for prasugrel (e.g., prior stroke/TIA, caution in older patients/low body weight).
Advanced Q28
Which is a common limitation of composite endpoints in ACS trials?
Composite endpoints bundle events of differing clinical importance; a positive composite may be driven by less important components, so interpretation requires examining each component.
Advanced Q29
Which trial evidence supports a risk-stratified early invasive approach in NSTE-ACS?
FRISC-II, RITA-3, TIMACS and pooled analyses support an early invasive strategy for many higher-risk NSTE-ACS patients, shaping guideline recommendations.
Advanced Q30
Which trial-era factor can make older ACS trial results less applicable today?
Changes in stent types, P2Y12 agents, anticoagulant options, and procedural techniques over time can affect applicability of older trial findings to current practice.
Advanced Q31
What is an important interpretation when a trial shows ischemic benefit but increased bleeding?
Net clinical benefit requires balancing ischemic risk reduction against bleeding risk; patient factors and shared decision making guide therapy choice and duration.
Advanced Q32
Which approach is recommended when a trial records a signal in a post-hoc subgroup but the overall trial is neutral?
Post-hoc subgroup findings require validation; they should inform further research and cautious clinical consideration but not automatic practice change.
Advanced Q33
Which trial taught that routine invasive strategies should be tailored rather than universal in NSTE-ACS?
TIMACS and similar trials supported that high-risk NSTE-ACS patients benefit from earlier invasive management, highlighting risk-stratified care.
Advanced Q34
Which endpoint is essential to report alongside ischemic outcomes in ACS trials to understand net benefit?
Reporting major bleeding (with standardized scales) is critical to assess safety and net clinical benefit when treatments affect both ischemic and bleeding risks.
Advanced Q35
Which trial outcome influenced reduced enthusiasm for routine thrombectomy despite initial positive surrogate signals?
Despite favorable angiographic surrogates, large randomized trials showed no improvement in hard outcomes, which outweigh surrogate or physiologic signals in routine practice.
Advanced Q36
Which trial nuance matters when considering ticagrelor vs prasugrel for a patient undergoing PCI?
Choice between ticagrelor and prasugrel considers trial populations, bleeding risk, planned CABG, and other clinical factors rather than a one-size-fits-all rule.
Advanced Q37
Why is operator experience important when interpreting access-site radial vs femoral trial results?
Trial outcomes for access-site strategies depend on operator skill; centers with high radial expertise see greater reductions in complications.
Advanced Q38
A trial shows a statistically significant relative risk reduction but small absolute difference. What should clinicians consider?
Absolute effects (ARR, NNT) provide context on real-world impact and help weigh benefits versus harms for individual patients, especially when baseline risk is low.
Advanced Q39
Which is a valid reason to withhold a trial therapy from a particular patient despite overall trial benefit?
Exclusion criteria and subgroup signals (e.g., prior stroke with prasugrel) are legitimate reasons to avoid a therapy in specific patients despite overall trial benefit.
Advanced Q40
What is the best single summary when trials show heterogeneous results across eras for similar interventions?
Heterogeneity across eras requires clinicians to contextualize evidence with current techniques, adjunctive therapies, and patient characteristics before changing practice.
End of 40 questions. Use keyboard (Tab/Enter) or mouse to select answers. Correct answer will be highlighted and explanation shown immediately.
Key Trials in Acute Coronary Syndrome — Summary Table
| Trial | Year | Population / Setting | Intervention vs Comparator | Primary Outcome | Key Findings | Clinical Impact |
|---|---|---|---|---|---|---|
| TIMI I–III | 1985–1990 | STEMI, UA/NSTEMI | Thrombolytics & early invasive vs conservative | Mortality, reinfarction | Early use of thrombolytics reduces mortality | Established thrombolysis as standard for early MI |
| GUSTO I | 1993 | STEMI early presentation | tPA vs streptokinase | 30-day mortality | tPA reduced mortality vs SK | tPA became preferred fibrinolytic |
| GUSTO IIb | 1996 | NSTEMI | Early invasive vs conservative | Death/MI | Early invasive reduced composite endpoint | Supported early invasive approach |
| GUSTO III | 1997 | STEMI | Reteplase vs Alteplase | 30-day mortality | No difference | Both acceptable thrombolytics |
| ISIS-2 | 1988 | STEMI | Aspirin, streptokinase | Vascular mortality | Aspirin + SK dramatically reduced mortality | Aspirin became mandatory therapy |
| ISIS-3 | 1992 | STEMI | SK vs tPA | 35-day mortality | No major difference | Both thrombolytics viable; cost considerations |
| ISIS-4 | 1995 | STEMI | ACE-I (captopril), nitrates | Mortality | Captopril reduced mortality | Universal ACE-I adoption in MI |
| MERLIN-TIMI 36 | 2006 | NSTEMI | Ranolazine | CV death/MI | No mortality benefit; ↓ angina | Symptom relief, not mortality |
| FRISC-II | 1999 | NSTEMI | Early invasive vs conservative | Death/MI | Significant reduction | Major support for early invasive strategy |
| RITA-3 | 2002 | NSTEMI/UA | Invasive vs conservative | Death/MI/refractory angina | Benefit mainly in high-risk | Risk-stratified invasive strategy |
| TACTICS-TIMI 18 | 2001 | NSTEMI with biomarkers | gpIIb/IIIa + early invasive vs conservative | Death/MI | Benefit strongest with elevated troponin | Troponin-guided invasive approach |
| OASIS-6 | 2006 | STEMI | Fondaparinux vs heparin | Death/reinfarction | Benefit except in primary PCI pts | Fondaparinux became option in non-PCI settings |
| OASIS-5 | 2006 | NSTEMI | Fondaparinux vs enoxaparin | Death/MI | Similar ischemic outcomes but ↓ bleeding | Bleeding reduction advantage |
| OASIS-7 | 2010 | ACS (PCI planned) | Double vs standard clopidogrel | CV death/MI | Benefit in STEMI, harm (bleeding) in others | Tailored clopidogrel dosing |
| PLATO | 2009 | ACS | Ticagrelor vs clopidogrel | CV death/MI/stroke | Ticagrelor superior | Ticagrelor first-line in ACS |
| TRITON-TIMI 38 | 2007 | ACS PCI | Prasugrel vs clopidogrel | CV death/MI/stroke | ↓ ischemic events but ↑ bleeding | Prasugrel for young/low-bleed-risk |
| ISAR-REACT 5 | 2019 | ACS planned PCI | Prasugrel vs ticagrelor | Death/MI/stroke | Prasugrel superior | Renewed interest in prasugrel |
| CURE | 2001 | NSTEMI | Clopidogrel + aspirin vs aspirin | CV death/MI/stroke | Significant reduction | DAPT standard established |
| CLARITY-TIMI 28 | 2005 | STEMI thrombolysis | Clopidogrel vs placebo | Occluded artery after lysis | Better patency, ↓ events | Added clopidogrel to lysis regimen |
| COMMIT/CCS-2 | 2005 | STEMI large-scale | Clopidogrel + aspirin | Death/MI/stroke | Significant mortality reduction | Universal DAPT after MI |
| STREAM | 2013 | STEMI early presenters | Pharmaco-invasive vs primary PCI | Death/MI | Equivalent outcomes | Validated pharmaco-invasive strategy |
| EXAMINE | 2013 | ACS + diabetes | Alogliptin | CV events | Neutral | No CV benefit |
| PARADISE-MI | 2021 | STEMI/NSTEMI with LV dysfunction | Sacubitril/valsartan vs ramipril | CV death/HF | No superiority | Still ACE-I/ARB standard |
| ATLAS ACS 2–TIMI 51 | 2009 | ACS + PCI | Rivaroxaban 2.5 mg | CV death/MI | ↓ ischemic events but ↑ bleeding | Added low-dose rivaroxaban option |
FAQs on Acute Coronary Syndrome (ACS) Trials
(Each FAQ contains 5 key points)
FAQ 1 — What was the main objective of the TIMI trials?
- Evaluate thrombolytic efficacy in STEMI.
- Compare early invasive vs conservative strategies.
- Establish biomarkers for risk stratification.
- Standardize composite CV endpoints.
- Develop validated TIMI risk scores.
FAQ 2 — What did the GUSTO-I trial establish?
- tPA superior to streptokinase.
- 30-day mortality reduction.
- Faster reperfusion with fibrin-specific agents.
- Led to global adoption of tPA.
- Landmark trial in thrombolysis era.
FAQ 3 — Why is ISIS-2 considered one of the most important ACS trials?
- Proved mortality benefit of aspirin in STEMI.
- Synergistic effect with streptokinase.
- Massive sample size (>17,000).
- Simple, pragmatic design.
- Made aspirin mandatory in all ACS.
FAQ 4 — What was shown in FRISC-II?
- Early invasive strategy improved outcomes.
- Reduced death/MI.
- Benefit sustained long term.
- Stronger effect in high-risk patients.
- Standardized early angiography in NSTEMI.
FAQ 5 — What is the significance of TACTICS-TIMI 18?
- Troponin-guided invasive strategy.
- Benefits of early glycoprotein IIb/IIIa inhibitors.
- Early invasive reduces death/MI.
- High-risk biomarker patients benefit most.
- Reinforced NSTEMI risk stratification.
FAQ 6 — What did PLATO show regarding ticagrelor?
- Superior to clopidogrel in ACS.
- Reduced CV death/MI/stroke.
- Benefit seen early and sustained.
- More non-CABG bleeding.
- Became guideline-preferred P2Y12 inhibitor.
FAQ 7 — What is the main takeaway from TRITON-TIMI 38?
- Prasugrel superior to clopidogrel.
- Reduced stent thrombosis.
- Higher bleeding risk.
- Avoid in prior stroke/TIA.
- Young, low-bleeding-risk patients benefit most.
FAQ 8 — What did ISAR-REACT 5 conclude?
- Prasugrel better than ticagrelor.
- Lower death/MI/stroke.
- Similar bleeding rates.
- Challenged prior ticagrelor-first strategies.
- Renewed interest in prasugrel in ACS PCI.
FAQ 9 — What were the key findings of CURE?
- Clopidogrel + aspirin > aspirin alone.
- Significant reduction in death/MI/stroke.
- Benefits seen across all NSTEMI risk groups.
- Bleeding increased but acceptable.
- Established DAPT as standard.
FAQ 10 — What did CLARITY-TIMI 28 show?
- Clopidogrel improved artery patency after lysis.
- Reduced recurrent ischemia.
- Reduced need for urgent PCI.
- Benefit in STEMI thrombolysis cohorts.
- Cemented clopidogrel in lysis-based strategies.
FAQ 11 — What did COMMIT/CCS-2 demonstrate?
- Massive study (>45,000 STEMI).
- Clopidogrel + aspirin reduced mortality.
- Benefit across all subgroups.
- Very low bleeding signal.
- Made clopidogrel universal post-MI.
FAQ 12 — What did STREAM establish about pharmaco-invasive therapy?
- Thrombolysis → early PCI equivalent to primary PCI.
- Important for rural/remote settings.
- Early rescue PCI crucial.
- Lower bleeding with dose-adjusted lysis.
- Supported pharmaco-invasive approach in early presenters.
FAQ 13 — What did OASIS-5 show?
- Fondaparinux vs enoxaparin.
- Similar ischemic outcomes.
- Major bleeding significantly reduced.
- Net clinical benefit favoring fondaparinux.
- Became preferred anticoagulant in NSTEMI (unless PCI).
FAQ 14 — What is the risk of using fondaparinux in primary PCI (OASIS-6)?
- Catheter thrombosis risk.
- Not recommended in primary PCI.
- Benefit only in non-PCI STEMI.
- Lower bleeding vs heparin.
- Selective use emphasized.
FAQ 15 — What did GUSTO-IIb teach about NSTEMI?
- Early invasive strategy improves outcomes.
- Validated risk-based selection.
- Identified value of troponins.
- Lower death/MI composite.
- Important foundation for NSTEMI guidelines.
FAQ 16 — What was the main finding of GUSTO-III?
- Reteplase = alteplase.
- No difference in mortality.
- Both acceptable lytics.
- Safety profile comparable.
- Choice influenced by logistics.
FAQ 17 — Why was ISIS-4 important?
- Tested captopril, nitrates, magnesium.
- ACE-I significantly reduced mortality.
- No benefit from magnesium/nitrates.
- ACE-I became standard in MI.
- Emphasized long-term remodeling prevention.
FAQ 18 — What did MERLIN-TIMI 36 show about ranolazine?
- Ranolazine safe in ACS.
- No mortality benefit.
- Reduced angina episodes.
- Lower arrhythmia burden.
- Primarily symptomatic relief agent.
FAQ 19 — What were the goals of RITA-3?
- Invasive vs conservative strategy.
- Benefits mainly in high-risk NSTEMI.
- Long-term benefit sustained.
- Reinforced risk stratification.
- Complemented FRISC-II findings.
FAQ 20 — What did RITA-2 conclude about PCI vs medical therapy?
- PCI relieves angina faster.
- No mortality difference.
- Early MI slightly increased with PCI.
- Highlighted limitations of early PCI era.
- Set stage for stent trials.
FAQ 21 — What was the importance of the DANAMI trials?
- Demonstrated superiority of primary PCI over lysis.
- Supported regional STEMI networks.
- Emphasized door-to-balloon times.
- Transport to PCI centers recommended.
- Foundation of modern STEMI systems.
FAQ 22 — What did EARLY ACS show about eptifibatide?
- Early routine GP IIb/IIIa not beneficial.
- Higher bleeding risk.
- No improvement in outcomes.
- Shift toward selective use.
- Changed antiplatelet timing strategies.
FAQ 23 — What did ATLAS ACS 2–TIMI 51 demonstrate?
- Rivaroxaban 2.5 mg reduced ischemic events.
- Increased bleeding.
- Significant mortality benefit.
- Best for high-ischemic-risk/low-bleeding-risk.
- Added “dual-pathway inhibition” concept.
FAQ 24 — What was the key insight from ACCOAST?
- Pre-treatment with prasugrel harmful.
- Increased bleeding.
- No ischemic benefit.
- Avoid prasugrel before angiography.
- Influenced timing of P2Y12 loading.
FAQ 25 — What did PARADISE-MI reveal about sacubitril/valsartan?
- No superiority vs ramipril.
- Trend toward benefit not significant.
- Safe in early post-MI setting.
- Heart failure prevention unchanged.
- ACE-I/ARB remain post-MI standard.
FAQ 26 — What did EXAMINE show about alogliptin?
- Neutral CV outcomes.
- No increase in HF.
- Safe in ACS diabetics.
- No mortality benefit.
- Reinforced neutrality of DPP-4 inhibitors.
FAQ 27 — What did PEGASUS-TIMI 54 establish about long-term ticagrelor?
- Long-term DAPT reduces recurrent MI.
- Increased bleeding.
- Best for high ischemic risk.
- Supports prolonged therapy beyond 12 months.
- Informs DAPT score decisions.
FAQ 28 — What was shown in GLOBAL LEADERS?
- Monotherapy strategy with ticagrelor tested.
- No superiority vs standard DAPT.
- Lower bleeding trend.
- Complex interpretation.
- Did not change guidelines.
FAQ 29 — What did TWILIGHT demonstrate?
- Ticagrelor monotherapy after PCI reduces bleeding.
- No increase in ischemic events.
- High-risk PCI populations benefit.
- Supported de-escalation strategy.
- Practice-changing in complex PCI.
FAQ 30 — What did TOMAHAWK show for OHCA?
- Immediate angiography not beneficial.
- No difference in mortality.
- Reinforces selective angiography.
- Broad ACS mimic population.
- Avoid routine cath in non-shock OHCA.
FAQ 31 — What did COMPLETE show in STEMI with multivessel disease?
- Complete revascularization reduces events.
- Lower CV death/MI.
- Benefit in staged or index admission.
- Landmark for multivessel PCI.
- Routine culprit-only strategy outdated.
FAQ 32 — What did PRAMI demonstrate?
- Preventive PCI reduced events.
- Supports multivessel PCI.
- Earlier evidence preceding COMPLETE.
- CV benefit consistent.
- Reinforced concept across trials.
FAQ 33 — What did iFR-SWEDEHEART show?
- iFR non-inferior to FFR.
- Faster, no hyperemia needed.
- Equal long-term outcomes.
- Simplified physiology-based PCI.
- Increased adoption of iFR.
FAQ 34 — What did DEFINE-FLAIR conclude?
- iFR = FFR for guidance.
- Less patient discomfort.
- Shorter procedure time.
- Similar clinical outcomes.
- Established iFR in guidelines.
FAQ 35 — What did SYNTAX (ACS subgroup) reveal?
- PCI vs CABG outcomes vary by complexity.
- Low SYNTAX: PCI acceptable.
- High SYNTAX: CABG superior.
- Stroke higher in CABG.
- Supported anatomical risk scoring.
FAQ 36 — What did EXCEL show (Left Main ACS subset)?
- PCI non-inferior to CABG.
- Controversial long-term results.
- Used new-generation DES.
- Low–intermediate complexity favored PCI.
- Multidisciplinary heart team essential.
FAQ 37 — What did NOBLE conclude about Left Main PCI?
- PCI inferior to CABG at long-term follow-up.
- Higher repeat revascularization.
- Similar early outcomes.
- Conflicts with EXCEL findings.
- Highlights need for individualized strategy.
FAQ 38 — What did VALIANT show post-MI?
- Valsartan as effective as ACE-I.
- Alternative when ACE-I intolerant.
- Benefit in LV dysfunction.
- Reduced mortality/HF hospitalizations.
- ACE-I/ARB both valid choices.
FAQ 39 — What did EPHESUS conclude about eplerenone?
- Reduced mortality post-MI.
- Especially beneficial in LV dysfunction.
- Reduced sudden death.
- Less gynecomastia than spironolactone.
- Standard for post-MI HF with low EF.
FAQ 40 — What did FOURIER reveal (ACS subgroup)?
- PCSK9 inhibitor evolocumab lowered events.
- Dramatic LDL reduction.
- Benefit seen early.
- Safe long-term profile.
- Confirmed LDL hypothesis in ACS secondary prevention.
