BCIS literature review

August 2025

Authors: Dr. Natalia Briceno, Dr. Andrew Chapman, Dr. Richard Jabbour

VALVULAR HEART DISEASE

DAPA TAVI

Dapagliflozin After Transcatheter Aortic Valve Implantation

 

Rationale

• Patients who undergo TAVI are at increased risk of heart failure admission post‑procedure.
• SGLT‑2 inhibitors improve outcomes in patients with heart failure.
• The trial aimed to test whether adding dapagliflozin post‑TAVI could reduce HF events and mortality

Publication date

• Raposeiras-Roubin Set al; DapaTAVI Investigators. Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med. 2025 Apr 10;392(14):1396-1405.
• gov number: NCT04696185

Study design

• Multicentre Spanish RCT
• Independent
• Pragmatic, open‑label, blinded endpoint adjudication
• 39 Spanish Centres between January 2021 and December 2023.

Trial info

• Population: Elderly patients (median age ~82 years, ~49% women) with severe aortic stenosis undergoing TAVI, and a history of HF hospitalization.
• Sample size:
• 1,222 patients in primary analysis: 1:1 randomisation dapagliflozin versus standard of care
• 605 dapagliflozin vs 617 standard care

Inclusion criteria

• Severe aortic stenosis undergoing TAVI
• Prior HF admission and one of the following:
  • Left ventricular ejection fraction ≤ 40% or
  • Diabetes mellitus or
  • Estimated glomerular filtrate rate 25-75 ml/min/1.73 m2

Exclusion Criteria:

• Known allergy or intolerance to SGLT2 inhibitors.
• Concomitant therapy with sulfonylurea or SGLT2 inhibitors.
• Systolic blood pressure < 100 mmHg or diastolic blood pressure < 50 mmHg.
• An estimated glomerular filtration rate (GFR) below 25 ml per minute per 1.73 m2.
• Chronic cystitis and/or recurrent urinary tract infections (2 or more in the last year)
• Poor control of diabetes mellitus that requires SGLT-2 inhibitor prescription on discharge according to treating physician judge.
• Any medical condition that, in the investigator´s judgment, would seriously limit life expectancy (less than one year).
• Pregnant or breast-feeding patients
• Patients participating in other clinical trials.

Primary endpoint

• The primary outcome was a composite of all-cause mortality and worsening HF (including hospitalization for HF or an urgent visit resulting in intravenous therapy for HF).

Results

• Primary outcome: Occurred in 15.0% of the dapagliflozin group vs 20.1% in control (HR 0.72; P = 0.02)
• Worsening HF component: 9.4% vs 14.4% (HR, 0.63; 95% CI, 0.45 to 0.88)
• All‑cause mortality: 7.8% vs 8.9% (HR, 0.87; 95% CI, 0.59 to 1.28) [not statistically significant]
• Other secondary outcomes (e.g. cardiovascular death or HF hospitalization) also trended favourably but were generally non-significant individually

 

Limitations

• Conducted exclusively in Spain – may affect generalizability
• Open‑label design could introduce bias even though the endpoints were adjudicated blindly
• Majority of benefit driven by HF events rather than all-cause mortality
• Approximately 20% discontinued dapagliflozin by one year due to known side effects of SGLT2 inhibitors

Conclusions

• In elderly post‑TAVI patients with prior heart failure and additional comorbidity, adding dapagliflozin 10 mg daily resulted in a 28% reduction in the composite of death or HF worsening at 1 year
• This was driven primarily by fewer HF events
• Treatment proved generally safe, though hypotension and genital infections were more frequent.
• These findings support consideration of SGLT‑2 inhibitors as adjunct medical therapy in this population.

 

VALVULAR HEART DISEASE

EVOLUT LOW RISK 5 YEAR OUTCOMES

Rationale

• To determine whether the supra‑annular, self-expanding Evolut TAVR system (CoreValve/Evolut R/Evolut PRO) maintains safety and efficacy compared to surgical aortic valve replacement (SAVR) up to five years in patients with severe aortic stenosis determined to below surgical risk (defined as: STS‑PROM score < 3%)

Publication date

• Forrest JK, et al; Low Risk Trial Investigators. 5-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis. J Am Coll Cardiol. 2025 Apr 22;85(15):1523-1532.
• Clinical Trgov: NCT02701283

Study Design

Trial info

• A prospective, international, randomized, multicentre trial comparing Evolut TAVR versus SAVR in low-risk patients.
• Valve types evolved over time (CoreValve, Evolut R, Evolut PRO)
• Follow-up extended through 5 years
• Low‑surgical‑risk (STS-PROM < 3%) patients with severe symptomatic aortic stenosis; mean age ~74 years; ~35% female
• 86 centres across U.S., Canada, Europe, Japan, Australia, New Zealand
• 1,414 randomized; 730 TAVI, 684 SAVR.
• 5 years follow up available for ~91% TAVI vs 87% SAVR patients (~671 TAVR, 598 SAVR)

Inclusion criteria

• Severe symptomatic aortic stenosis
• Estimated low surgical risk (< 3% 30-day mortality by STS score)
• Heart Team–determined suitability for both TAVI and SAVR

Selected exclusion criteria

• Patients with severe comorbidities
• Anatomical contraindications to TAVR
• Life expectancy < 1 year

Primary endpoint

Composite of all-cause mortality or disabling stroke at 5 years

Results

• Five‑year composite endpoint (primary):
  • 5% (TAVI) vs 16.4% (SAVR), P = 0.47
• All‑cause mortality:
  • 5% (TAVI) vs 14.9% (SAVR), P = 0.39
• Disabling stroke:
  • 6% (TAVI) vs 4.0% (SAVR); P = 0.57
• Cardiovascular mortality:
  • 2% (TAVI) vs 9.3% (SAVR), P = 0.15
• Non‑cardiovascular mortality:
  • 8% (TAVI) vs 6.2% (SAVR), P = 0.73
• Valve performance:
  • TAVI had significantly lower mean gradients: 10.7mmHg (TAVI) vs 12.8 mmHg (SAVR), P < 0.001
  • In addition, larger effective orifice areas 2.1 (TAVI) vs 1.9 cm² (SAVR), P < 0.001
• Paravalvular regurgitation (PVL):
  • Mild or greater PVL higher after TAVI (~17.0%) vs SAVR (~5.7%), P<0.001
• Reintervention rates:
  • 3% (TAVI) vs 2.5% (SAVR), P = 0.44
• Quality of life:
  • KCCQ scores 88.3% (TAVI) vs 88.5 (SAVR)
• PPM rates:
  • 27% (TAVI) vs 13% (SAVR), P <0.001

Comments

• Loss to follow‑up higher in control arm (~9% TAVR, ~13% SAVR) may bias long-term data; however, analysis with withdrawn patients excluded changed all-cause mortality rates to 14.7% vs 15.2%, P = 0.74 (Still non-significant)
• Mild+ PVL was higher after TAVI, without clear clinical impact
• Implantation techniques have improved over time with lower pacemaker rates in contemporary TAVI implants with the cusp overlap technique
• Longer-term (beyond five years) valve durability and structural integrity—in low-risk, younger populations—remain to be fully established with 10‑year follow-up and is eagerly awaited

Conclusions

• At five years, in low-surgical-risk patients with severe aortic stenosis, the Evolut TAVI system showed comparable outcomes to surgery for the primary composite endpoint of all‑cause mortality or disabling stroke.
• TAVI demonstrated favourable hemodynamic, sustained quality-of-life benefits, and no significant increase in reinterventions, with an increase in PVL and PPM rates but overall low rates of valve failure.
• These data support TAVI as a durable and effective alternative to surgery in low-risk patients over intermediate-term follow‑up

 

VALVULAR HEART DISEASE

BHF PROTECT TAVI TRIAL

 

Rationale

• To determine the effectiveness of a cerebral embolic protection (CEP) device in the reduction of acute stroke in patients with severe aortic stenosis who were undergoing transcatheter aortic valve implantation (TAVI).

Publication date

• Kharbanda RK on behalf of the BHF PROTECT-TAVI Investigators. Routine Cerebral Embolic Protection during Transcatheter Aortic-Valve Implantation. N Engl J Med 2025;392:2403-2412.
• Registered at ISRCTN16665769

Study Design

Trial information

• A prospective multi-centre randomised controlled trial at 33 sites across the United Kingdom
• Pragmatic design aiming to recruit an all-comers population
• Parallel group randomisation – CEP device versus no CEP device
• Device: Sentinel CEP (Boston Scientific) deployed via the right radial artery with filters covering the left common carotid artery and the right innominate artery.
• 7,635 patients randomised: 3,815 CEP and 3,820 no CEP
• Stroke ascertainment by the Questionnaire to Verify Stroke Free Status (QVSFS) in addition to routine clinical review

Inclusion criteria

• Severe aortic stenosis scheduled for TAVI (via any access route where cerebral embolic protection (CEP) may be used).
• Clinically and anatomically suitable for Sentinel CEP (as per treating clinician)
• Aged 18 years or above
• Willing and able to give informed consent

 

Selected exclusion criteria

• No specific exclusion criteria

Primary outcome

• The incidence of stroke at 72-hours post-TAVI (or hospital discharge if sooner)

Results

• Similar baseline and procedural characteristics in the intervention and control arms
• Transfemoral TAVI in 99.3 versus 99.4%
• Valve in valve in 3.8% versus 3.2%
• Balloon-expandable valve used in 57.4 versus 57.3%
• Procedure duration 62 mins (48 to 81) versus 52 mins (39 to 70 mins)
• The primary endpoint occurred in 2.1% (81/3,795) in the CEP group and 2.2% (82/3,799) in the control group [difference -0.02%, 95%CI -0.68 to 0.63; P=0.94].
• There was no difference in secondary outcomes including
  • Disabling stroke at 6-8 weeks (-0.2%, 95%CI -0.7 to 0.4)
  • Severe stroke within 72 hours or before discharge (0.0%, 95%CI -0.3 to 0.3)
  • Death within 72 hours or before discharge (0.1%, 95%CI -0.3 to 0.5)
  • Death or stroke within 72 hours or before discharge (0.1%, 95%CI -0.6 to 0.8)
  • Death, stroke or TIA within 72 hours or before discharge (0.2%, 95%CI -0.6 to 1.0)
• There were no major adverse safety signals from device use
  • Access site complications occurred before hospital discharge occurred in 8.1% (304/3,772) in the CEP group and 7.7% (290/3,776) in the control group (difference 0.4%, 95%CI -0.8 to 1.6).
  • Access site complications after discharge within 6 to 8 weeks occurred in 0.8% (27/3,347) in the CEP group and 0.4% (13/3,378) patients in the control group (difference 0.4%, 95%CI 0.1 to 0.8).

Comments

• Large, multi-centre, pragmatic trial across 33 sites in the United Kingdom.
• Event rate consistent with population level estimates from UK TAVI registry
• Population representative of routine practice
• No evidence of learning effect in centres with less familiarity with CEP
• There was some interruption due to COVID-19 and there was limited diversity

Conclusions

• Routine use of CEP was not associated with a reduction in incident stroke within 72 hours or prior to discharge from hospital after TAVI. This robust assessment of this device therapy is consistent with prior trial data and suggests routine CEP does not have a role in elective TAVI.

CORONARY ARTERY DISEASE

RIVAWAR

Rationale:

• To investigate the efficacy of the direct oral anticoagulant rivaroxaban as compared with warfarin in patients with acute LV thrombus at 12 weeks, to guide anticoagulant therapy in this population.

 

Publications details:

• Shah JA, Hussain J, Ahmed B, Batra MK, Ali G, Naz M, Khan W, Bhatti KI, Karim M, Hakeem A. Rivaroxaban vs Warfarin in Acute Left Ventricular Thrombus Following Myocardial Infarction: RIVAWAR, An Open-Label RCT. JACC Adv. 2025 Jul 23;4(8):101978. doi: 10.1016/j.jacadv.2025.101978. Epub ahead of print. PMID: 40706143; PMCID: PMC12309278.

 

Study design:

• Open label, non inferiority, parallel-group randomised control trial
• Investigator initiated
• Participants randomised 2:1 to receive rivaroxaban (20mg) or warfarin (target INR 2-3) for 12 weeks

 

Trial Information:

• 261 patients randomised, 171 in the rivaroxaban group and 90 in warfarin group
• Conducted in the National Institute of Cardiovascular Disease in Pakistan, which is a large volume (>10,000 yearly PPCI) centre
• Recruitment from June 7 2021 to December 31 2023
• Patients treated with warfarin or rivaroxaban alongside standard DAPT consisting of aspirin and clopidogrel
• Intervention period included 4 weeks of triple therapy, followed by single antiplatelet with clopidogrel alongside allocated anticoagulant for the remaining 8 weeks.
• Patients started on GDMT for LV dysfunction
• Follow up: weekly telephone consultations, with in person visit every 2 to 4 weeks. Follow up echo at 4 and 12 weeks.
• Resolution of thrombus defined as no visualisation of LVT on apical 4 chamber, 2 chamber, 3 chamber and 4 chamber off axis views on 2D echo.
• Bleeding events monitored alongside MACE
• Per protocol analysis
• No crossovers

 

Inclusion:

• Confirmed diagnosis of STEMI or NSTEACS
• Detected LVT on echocardiography within 7 days of acute MI

 

Exclusion:

• Refusal to consent
• Cardiogenic shock at time of LV thrombus diagnosis
• Prior major or intracranial bleeding
• Advanced CKD (eGFR <30mL/min)
• Other indications for anticoagulation

 

Outcomes:

• Primary end point: Complete resolution of left ventricular thrombus assessed by echocardiography at 12 weeks
• Secondary outcomes all cause mortality, stroke and bleeding events

 

Results:

• 314 screened with acute LVT and 216 met inclusion criteria. 171 randomized to rivaroxaban and 90 were randomized to warfarin group.
• Baseline characteristics similar, with age, sex and type of MI matched.
• Majority of patients presenting with STEMI and having severe LVSD
• Mean age 54.5 +/- 10.7 years
• PCI performed in 85.1% of patients
• Median INR 2.4 in those on warfarin
• At 4 weeks, 20% of patients in rivaroxaban arm and 8.3% in the warfarin arm had complete resolution of LVT. P-value for non inferiority = 0.017. No difference at 12 weeks.
• Safety outcomes and all cause mortality not statistically different between groups
• Rates of ischaemic stroke numerically higher in rivaroxaban group than warfarin, but not statistically significant.
• Major bleeding in 2.3% in rivaroxaban cohort and 1.1% in warfarin cohort
• 2 intracranial bleeds in rivaroxaban and none in warfarin cohort.

 

Conclusions:

• Rivaroxaban has been shown to be non-inferior to warfarin in treatment of acute LVT
• There is evidence to suggest that rivaroxaban leads to a quicker resolution, with a higher percentage of patients having resolution of thrombus at 4 weeks
• Numerically although not statistically significant more bleeding events and ischaemic strokes, which is comparable to previous DOAC trials, with no difference in all cause mortality.

 

Limitations:

• 2:1 randomization imbalance
• Single centre
• Short follow up

 

Comments:

• Higher rates of thrombus resolution compared to other studies, however only enrolled acute MI and less sensitive modality used to assess thrombus.
• Due to 2:1 randomisation design, smaller warfarin cohort with wider CI
• 4 weeks of triple therapy may have had an impact on safety outcomes especially in those with higher risk of bleeding, now ESC advise one week of triple therapy.

Further studies needed to investigate the safety signal with larger numbers, with more sensitive imaging modalities used alongside evaluation of treatment duration.

CORONARY ARTERY DISEASE

Pressure derived indices in the left main coronary artery

 

Rationale:

• The left main coronary artery subtends a large area of myocardium and is prognostically important, and historically its assessment has been based on anatomical diameter stenosis. There is low use of invasive physiology for assessment of left main disease, and paucity of data on how best to assess.
• Authors sought to investigate whether invasive pressure based indices are similar in both the left anterior descending artery and left circumflex in patients with isolated left main coronary artery disease, and whether any differences are as a result of differences in microvascular function in the territories they supply.

 

Publications details:

• Demir OM, Sinha A, Rahman H, Ryan M, O’Gallagher K, Ellis H, Li Kam Wa M, Saraf S, Alfakih K, Webb I, Melikian N, De Silva K, Chiribiri A, Plein S, Perera D. Pressure-Derived Indices in the Left Main Coronary Artery: Insights From Comprehensive In Vivo Hemodynamic Studies of Diseased and Unobstructed Vessels. Circ Cardiovasc Interv. 2025 Jul;18(7):e015320

Study design:

• Prospective observational
• Invasive coronary physiology study
• Investigator initiated

 

Study Information:

• Conducted at St Thomas’ Hospital and Kings College Hospital, campuses of Kings College London
• Patients enrolled if they had an indication for an invasive coronary angiogram or percutaneous coronary intervention.
• Cardiac catheterization protocol
  • Right radial artery access
  • 1mg of midazolam and 70 units per kg of heparin
  • 400-600 mg of isosorbide dinitrite into left coronary artery
  • Indices measured using Verrata Plus Volcano 0.014-inch coronary wire
  • Paired LAD and LCx coronary physiological measurements obtained
  • Indices: In all patients FFR, iFR and manual pullback. In a subset of patients, coronary flow was measured using a dual doppler/pressure sensing guidewire (Combowire).
  • Resting measurements and measurements during hyperaemia induced by IV adenosine in both main daughter branches were obtained.
• Coronary flow velocity reserve defined as the ratio of hyperemic to resting average peak velocity.
• Microvascular resistance reserve calculated as CFvR dived by FFR, multiplied by basal aortic pressure dived by hyperaemic aortic pressure. Metric that characterises the vasodilator reserve capacity of the coronary microcirculation, while accounting for the influence of epicardial disease and impact of giving potent vasodilators to the aortic pressure.
• Hyperaemic microvascular resistance was calculated as distal coronary pressure divided by flow velocity during maximal hyperaemia.
• Sensitivity analyses performed, investigating potential effect of hydrostatic forces (using CTCA), the relationship between myocardial mass and MRR (cardiac MRI) and also pressure wire derived indices by anatomic location of LMCA stenoses.

 

Inclusion:

• Clinical indication for invasive coronary angiogram or PCI
• Isolated LMCA cohort
  • Atheroma angiographically and physiologically isolated to the LMCA (FFR pullback gradient £05 FFR units in both LAD and LCx
  • LMCA lesion contributed to ³80% of the total FFR in each vessel.
• Unobstructed cohort
  • Angiographically normal vessels
  • FFR >0.80 in both limbs
  • Normal microvascular function (LAD CFvR³0)

Exclusion:

• LVEF <50%
• ACS within 4 weeks
• Greater than mild valve disease
• Resting HR >120bpm
• Prior CABG
• Contraindication or intolerance to adenosine or contrast

 

Results:

• 80 patients enrolled (47 in LMCA cohort and 33 in unobstructed cohort)
• All patients in unobstructed cohort underwent dual pressure and Doppler assessment. 22 patients in LMCA cohort underwent dual pressure and Doppler coronary assessment.
• Patients in unobstructed group were younger and more likely to be female
• In patients with isolated LMCA disease, FFR in LAD 0.74±11 and in LCx 0.81±0.11 (p<0.0001). iFR values lower in LAD versus LCx also (0.89 versus 0.94).
• On pressure wire pullback, the pressure drop was higher between LAD and left main than between LCx and left main.
• Similar differences in the unobstructed cohort were observed with respect to resting and hyperaemic pressure based indices
• Rate of misclassification of functional significance if using only the LCx was 1 in 5 patients when using FFR and higher (28% of patients) when using iFR. All misclassification related to a significant LMCA lesion being judged as non significant.
• Within cohort -MRR values higher in LAD than in the LCx in both cohorts, minimal hyperaemic MR was also lower in LAD than in LCx, and maximal coronary flow and CFvR were higher in LAD in both cohorts
• Between cohort- MRR in LAD was similar in LAD in both unobstructed and LMCA patients. This was seen in LCx also.
• Myocardial mass and MRR were correlated.

 

Conclusions:

• Pressure wire derived physiological indices have been shown to be lower in the LAD as compared with the LCx in both patients with LMCA and those with unobstructed coronaries.
• Minimal microvascular resistance was also lower in the LAD (therefore higher CFvR in LAD) in both LMCA and unobstructed cohorts.
• These findings suggest that thresholds for diagnosing haemodynamically significant epicardial and microvascular dysfunction may be different in different vessels.

 

Limitations:

• Small number of patients studied
• Intracoronary imaging not performed and so patients with downstream atheroma not apparent on angiogram may have been included, alongside patients with LMCA that extends beyond the left main
• No outcome data obtained

 

Comments:

• Regardless of the presence of epicardial disease, pressure derived indices differ between the LAD and LCx, which was shown to be due to differences in coronary flow and microvascular resistance. This led to a 1 in 5 misclassification of the severity of LMCA if using solely LCx to assess functional significance.
• This supports prioritizing physiological assessment of the LAD in assessing isolated LMCA. It also has implications for the thresholds used for assessing functional significance of other bifurcations.
• There is a need for further research on physiological assessment of bifurcations including non-left main alongside evaluation of vessel specific thresholds.

 

CORONARY ARTERY DISEASE

SMART CHOICE

 

Rationale

• To define the optimal strategy for long-term antiplatelet maintenance in those who have previously underwent percutaneous coronary intervention (PCI), comparing the efficacy and safety of aspirin and clopidogrel.

Publication date

• Hong Choi et al. Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular events after percutaneous coronary intervention (SMART-CHOICE 3): a randomised, open-label, multicentre trial. Lancet 2025;405:1252-1263
• Registered at gov(NCT04418479)

 

Study Design

Trial information

• Prospective, investigator-initiated, multicentre, prospective, randomised open-label trial comparing clopidogrel and aspirin monotherapy in 26 sites in South Korea.
• 5,506 patients randomly allocated to clopidogrel or aspirin monotherapy
• Median time between PCI and randomisation was 17.5 months (IQR 12.6-36.1)
• Median follow up 2.3 years (IQR 1.6-3.0)

Inclusion criteria

• 19 years or older
• Successful PCI with drug eluting stent
• Standard duration DAPT (≥12 months for MI and ≥6 months for any other PCI)
• No cardiovascular events after PCI

 

At least one complex coronary lesion:

-True bifurcation lesion (>2.5mm)

-Chronic total occlusion

-Unprotected left main disease

-Long lesion >38mm

-Multivessel PCI

-Multiple stents
-In-stent restenosis
-Severely calcified lesions
-Ostial lesions of major epicardial artery

Or
-At high risk of recurrent ischaemic event

-Previous MI

-Medication treated diabetes

Selected exclusion criteria

-Long-term treatment with oral anticoagulants

-Use of DAPT for any other indication than coronary disease

-Use of single antiplatelet at screening

-Contraindication to aspirin or clopidogrel

Primary outcome

• Cumulative incidence of death from any cause, myocardial infarction or stroke

Results

• Primary outcome: 4.4% (clopidogrel) vs 6.6% (aspirin) [hazard ratio 0.71, 95% CI 0.54 – 0.93, P=0.013].
• Death occurred in 2.4% (95% CI 1.6 – 3.1%) in the clopidogrel group and 4.0% (95% CI 2.9 – 5.0%) in the aspirin group (HR 0.71, 95%CI 0.49 – 1.02)
• Myocardial infarction occurred in 1.0% (95% CI 0.6 – 1.4%) in the clopidogrel group and 2.2% (95% CI 1.4 – 2.9%) in the aspirin group (HR 0.54, 95% CI 0.33 – 0.90)
• Stroke occurred in 1.3% (95% CI 0.7 – 2.0%) in the clopidogrel group and 1.3% (0.8 – 1.7%) in the aspirin group (HR 0.79, 95% CI 0.46 – 1.36)
• There was no increase in bleeding, which occurred in 3.0in the clopidogrel group and 3.0% in the aspirin group (HR 0.97, 95% CI 0.67-1.42).

Comments

• There is some uncertainty about the generalisability of this trial. Very few women were recruited (18.2%) and it exclusively recruited Korean participants but no difference in results when stratified by CYP2C19 allele
• Open label design – risk of bias in prescribing of gastroprotective therapies may have minimised bleeding effects
• Event rate was lower than anticipated
• Low rate of patients with high bleeding risk
• Results may not apply to these patients nor those with CKD
• No prespecified antiplatelet strategy in patients who had further PCI or anticoagulant therapy commenced.
• Median DAPT duration was long at 17.5 months prior to randomisation, which may have allowed selection of those patients at high bleeding risk to declare themselves, biasing results.

Conclusions

• In patients at high risk of ischaemic events following PCI, clopidogrel monotherapy was associated with a lower rate of death, myocardial infarction or stroke. The generalisability of these findings is limited to select populations and the results should be considered in the context of other evidence which supports a long term P2Y12 monotherapy strategy.

 

If you are a non-surgical centre looking to undertake Primary Percutaneous Coronary Intervention (PPCI), support and guidance are available. You are encouraged to reach out for assistance with planning, protocols, governance arrangements, or collaboration with surgical centres.

For advice and support, please contact:
BCIS Non-Surgical Centre Representative:

Abhishek Kumarabhishekkumar@nhs.net

Evidence-based recommendations on intravascular lithotripsy to treat calcified coronary arteries during percutaneous coronary intervention. This involves using ultrasound shockwaves to break up hard deposits in the arteries, to allow blood to flow more freely.

LSA guidance evaluates categories of technologies that are already in widespread use within the NHS. It assesses whether price variations between technologies in a category are justified by differences in innovation, clinical effectiveness and patient benefits. This will support NHS commissioners, procurement teams and healthcare professionals to choose technologies that maximise clinical effectiveness and value for money.

BCIS are pleased to announce that the new PCI guidelines have now been published in ICR3 and can be accessed using the following link: PCI in the UK: Recommendations of the BCIS | ICR Journal. A great deal of work, involving many cardiologists, has gone into producing this document. We hope these updated guidelines will be a useful reference for hospitals across the country. PCI in the UK has been one of the success stories of the NHS and we hope these updated guidelines provide an updated  framework for safe and effective coronary intervention.

Best Wishes,

Gerald Clesham, Hon Sec

 

 

BCIS literature review

March 2025

Authors: Dr. Richard Jabbour, Dr. Claudia Cosgrove, Dr. Natalia Briceno

VALVULAR HEART DISEASE

 

EARLY TAVR

Treatment of severe aortic stenosis without symptoms

 

Rationale:

• The purpose of the study was to determine whether transcatheter aortic valve implantation (versus routine clinical monitoring) was beneficial in patients with severe asymptomatic aortic stenosis (stage C aortic stenosis).

 

Publication date:

• gov number, NCT03042104
• Généreux P, et al; EARLY TAVR Trial Investigators. Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis. N Engl J Med. 2025 Jan 16;392(3):217-227.

 

Study Design

• International
• Randomized 1:1
• Parallel
• Open label
• A total of 901 patients underwent randomization; 455 patients were assigned to TAVI and 446 to clinical surveillance.

 

Trial Info:

• 901 Patients included (1578 screened)
• Duration of follow-up: median 3.8 years
• Mean patient age: 75.8 years
• Median STS 1.8%
• 6% low surgical risk
• 30% female
• TAVI valve used: balloon expandable (SAPIEN 3 / SAPIEN 3 ultra)

Inclusion criteria:

• 65 years of age or older
• Severe aortic stenosis
• Patient asymptomatic (negative ETT or physician assessment if unable to perform stress test).
• LV ejection fraction ≥ 50%
• Society of Thoracic Surgeons (STS) risk score ≤ 10

 

Selected exclusion criteria:

• Patient is symptomatic
• Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
• Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV
• Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
• Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post TAVR
• Evidence of an acute myocardial infarction ≤ 30 days before randomization
• Aortic valve is unicuspid, bicuspid with unfavourable features for TAVR, or is non-calcified
• Severe aortic regurgitation (>3+)
• Severe mitral regurgitation (>3+) or ≥ moderate mitral stenosis
• Pre-existing mechanical or bioprosthetic valve in any position
• Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
• Inability to tolerate or condition precluding treatment with anti-thrombotic therapy
• Stroke or transient ischemic attack within 90 days of randomization
• Renal insufficiency and/or renal replacement therapy
• Active bacterial endocarditis within 180 days of randomization
• Severe lung disease or currently on home oxygen
• Severe pulmonary hypertension
• History of cirrhosis or any active liver disease
• Significant frailty as determined by the Heart Team
• Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system
• BMI >50 kg/m2
• Estimated life expectancy <24 months

 

Primary Endpoint:

Major adverse cardiac events: All-cause death, all stroke, and unplanned cardiovascular hospitalization at 2 years

 

Results:

• Primary end-point event: 122 patients (26.8%) in the TAVI group vs 202 patients (45.3%) in the clinical surveillance group (hazard ratio, 0.50; CI 0.40 to 0.63; P<0.001).
• All cause death: 8.4% TAVI vs 9.2% clinical surveillance (not significant)
• Stroke: 4.2% TAVI vs 6.7% clinical surveillance (not significant)
• Unplanned hospitalization for cardiovascular causes: 20.9% TAVI vs 41.7% clinical surveillance (HR 0.43; CI, 0.33-0.55)
• During a median follow-up of 3.8 years, 87% of patients in the clinical surveillance group underwent aortic-valve replacement.
• There were no differences in procedure-related adverse events between patients in the TAVI group and those in the clinical surveillance group who underwent aortic-valve replacement. No patients in either group died of CV causes within 30 days.
• Stroke incidence at 30 days: 0.9% TAVI vs 1.8% control group (converted to aortic valve replacement)

 

Limitations

• Unblinded trial driven by endpoint susceptible to bias
• No surgical arm in trial
• In real world practice ETT is often difficult to adopt in practice due to severe AS
• 87% of patients underwent TAVI in the control arm making it difficult to ascertain a true comparison between groups

 

Conclusions

• Among patients with asymptomatic severe aortic stenosis, a strategy of early TAVI was superior to clinical surveillance in reducing the incidence of death, stroke, or unplanned hospitalization for cardiovascular causes.
• The endpoint of the trial was driven by unplanned TAVR, a component which would be susceptible to bias in this unblinded trial
• Two surgical trials – RECOVERY and AVATAR also found early SAVR were beneficial, but these trials contained relatively small numbers of patients and were therefore underpowered to detect true differences between groups in hard endpoints.
• Notably, 87% of patients effectively received an aortic valve replacement in the clinical surveillance arm
• In young patients with asymptomatic severe AS, the issues regarding long term durability and risks of long-term PPM insertion remain
• There were no differences in death or stroke between groups which indicates that current practice may not change significantly based on these results.

 

TAVR UNLOAD

Treatment of moderate aortic stenosis without symptoms

Rationale:

• The purpose of the study was to explore whether transcatheter aortic valve implantation (SAPIEN 3 THV) was beneficial (compared with clinical surveillance / guideline-directed medical therapy) in patients with moderate stage B aortic stenosis and chronic systolic heart failure.

 

Publication date:

• gov number:NCT02661451
• Van Mieghem NM et al. Transcatheter Aortic Valve Replacement in Patients With Systolic Heart Failure and Moderate Aortic Stenosis: TAVR UNLOAD.J Am Coll Cardiol. 2024 Oct 22:S0735-1097(24)09960-1

 

Study Design

• Randomized, open label
• Parallel
• Investigator initiated
• International
• Enrolment period Jan 2017 – Dec 2022

 

Trial Information

178 Patients with chronic systolic heart failure and moderate aortic stenosis (stage B aortic stenosis) were randomized to TAVI with a balloon-expandable valve (n = 89) vs. clinical surveillance (n = 89).

• Total number of patients: 178
• Duration of follow-up: 23 months
• Mean patient age: 77 years
• Percentage female: 21%
• 6% NYHA III/IV
• Mean aortic valve area (baseline or dobutamine stress): 1.2 cm²in the TAVI group vs. 1.3 cm² in the clinical surveillance group
• Mean aortic valve gradient (baseline or dobutamine stress): 21.9 mmHg in the TAVI group vs. 21.9 mmHg in the clinical surveillance group

 

Inclusion criteria:

• Left ventricular (LV) ejection fraction (EF) < 50% at rest on appropriate guideline-directed medical therapy
• Heart Failure with NYHA class ≥ 2
• Moderate aortic stenosis (typically mean trans-aortic gradient (MG) ≥ 20 mmHg and < 40 mmHg at rest and aortic valve area (AVA) > 1.0 cm2 and ≤1.5 cm2 (or AVA < 1.0 cm2 but indexed AVA > 0.6 cm2) at rest)
• Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV

 

Exclusion criteria

• LVEF < 20% or persistent need for intravenous inotropic support
• Hospitalization for acute decompensated HF within 2 weeks prior to randomization
• Cardiac resynchronization therapy (CRT) device implantation within 1 month prior to randomization
• Coronary artery revascularization (PCI or CABG) within 1 month prior to randomization
• In need and suitable for revascularization per heart team consensus
• Severe aortic and/or mitral regurgitation
• Congenital unicuspid or congenital bicuspid aortic valve
• Concomitant non-aortic valvular disease with a formal indication for valve surgery per established guidelines (ESC/ACC/AHA)
• Previous aortic valve replacement (mechanical or bioprosthetic)
• Severe RV dysfunction
• Previous stroke with permanent disability (modified Rankin score ≥ 2)
• Severe lung disease as indicated by FEV1 <30% predicted or need for chronic daytime supplemental oxygen therapy
• Severe chronic kidney disease: glomerular filtration rate (GFR) < 30 mL/min by MDRD or need for renal replacement therapy
• Gastrointestinal (GI) bleeding within the past 3 months
• Liver cirrhosis Child-Pugh C
• Active systemic infection, including active endocarditis

Primary endpoint

• The primary endpoint was the hierarchical occurrence (win ratio) of:
• all-cause death
• disabling stroke
• disease-related hospitalizations and heart failure equivalents
• change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score analysed using the win ratio.

Results:

• At the longest follow-up, TAVI resulted in 47.6%-win pairs vs. 36.6% in the clinical surveillance group (p = 0.14).
• At 1-year follow-up, TAVR resulted in 48.0%-win pairs vs. 30.9% in the clinical surveillance group (p = 0.032). This was driven by QoL: Mean change in KCCQ at 1 year: 12.8 in the TAVI group vs. 3.2 in the clinical surveillance group (p = 0.018)
• At the longest follow-up, mean change in KCCQ: 10.9 in the TAVR group vs. 6.1 in the clinical surveillance group (p = 0.20)
• No patients died in TAVI group at 30 days, 1 (1.1%) disabling stroke).
• In the clinical surveillance group, 43% underwent TAVI at a median of 12 months (q1-q3 6-20months). 92% had progression to severe AS.

 

Limitations

• Small number of patients
• Underpowered to detected difference in treatment groups
• Trial stopped early due to issues with recruitment / funding
• Lack of sham control may have influenced the quality-of-life findings
• Study only performed with balloon-expandable (Sapien) valve

 

Conclusion:

•   TAVI was not superior to clinical surveillance with guideline directed medical therapy for the primary hierarchical composite endpoint in patients with moderate AS and heart failure with reduced ejection fraction at a median follow up of 23 months
• Performing TAVI in moderate aortic stenosis was however safe and may lead to improvements in quality of life
• When analysis was restricted to 1 year of follow-up, TAVI was associated with an improvement in the composite of clinical events and quality of life. This was driven by QoL with an improvement in KCCQ compared with clinical surveillance.
• The trial was relatively small and underpowered to detect a difference in hard endpoints between groups
• In the clinical surveillance group, 43% underwent TAVI at a median of 12 months. 92% had progression to severe AS.
• Further data is eagerly awaited: For example, the PROGRESS (NCT04889872) and EXPAND II (NCT05149755) trials are exploring the efficacy of TAVI (balloon-expandable and self-expanding devices) in patients with moderate AS.

 

CORONARY ARTERY DISEASE

 

DCB-BIF trial 

DCB use in side branches

Rationale:

• The aim of the trial was to evaluate whether a strategy of treating a pinched side branch during provisional stenting with a drug coated balloon improves outcomes as compared with a non-compliant balloon, in patients with simple, true coronary bifurcations.

 

Publication:

• Gao, X, Tian, N, Kan, J. et al. Drug-Coated Balloon Angioplasty of the Side Branch During Provisional Stenting: The Multicenter Randomized DCB-BIF Trial. JACC. 2025 Jan, 85 (1) 1–15. https://doi.org/10.1016/j.jacc.2024.08.067

 

Study Design

• International (22 centres; China, Italy, Indonesia, Republic of Korea)
• Randomized 1:1 stratified by diabetes, initial presentations and sites.
• Treatment allocation masked to all except for physician and staff in the cardiac catheterization laboratory.

 

Trial Information

• 784 patients included (1231 screened)
• Duration of follow-up: 12 months
• Paclitaxel coated balloon used
• Mean patient age: 65 years
• 3% female
• 6% had diabetes
• 1% had Median 1,1,1 bifurcation lesions
• Crossover from 1 stent to 2 stent strategy occurred in 3.3% of the DCB arm and 3.8% in the NCB group.
• Distal left mains made up 15.2% of cases enrolled.

 

Procedure:

• Provisional stenting according to the EBC recommendations
• SB pre dilatation not recommended
• Stenting of MV was followed by proximal optimisation technique (POT)
• Randomisation in cases where ostial SB diameter stenosis ≥70%
• In DCB group, 1:1 non-compliant balloon NCB) used to dilate ostium, with sufficient predilatation defined as less than or equal to 50% residual stenosis. Then DCB inflated for 60 seconds. Following DCB, kissing balloon inflation performed with 2 NCBs and re POT performed. Indications for SB rescue stenting included Type C dissection or TIMI flow grad less than 3.
• In NCB group, all steps the same except that a DCB was not used.

 

Inclusion criteria:

• Patients aged 18 or over
• Presentation with silent ischaemia, stable or unstable angina or acute myocardial infarction older than one week from onset of chest pain to admission.
• Target lesion simple and true bifurcation (Median 1,1,1; Medina 1,0,1; Medina 0,1,1). With reference vessel diameter greater than or equal to 2.5mm, baseline diameter stenosis greater than or equal to 50%, side branch lesion length less than 10mm, successful recanalization of CTO in other MV or SB before enrolment, ostial SB stenosis greater than or equal to 70% after stenting MV.

 

Selected exclusion criteria:

• Allergy to study balloon, stent or protocol required concomitant medications
• Intolerance to DAPT
• Life expectancy less than 12 months
• Pregnancy or breast feeding
• Re stenotic lesion
• Severe calcification requiring rotational atherectomy
• Haemodynamic instability.

 

Primary Endpoint:

• Major adverse cardiac events at 12 months following the procedure, encompassing cardiac death, target vessel MI or clinically driven target-lesion revascularisation.

 

Results:

• Baseline characteristics well matched between groups.
• Luminal gain was slightly higher in SB in the DCB arm (p=0.041) as assessed by quantitative coronary analysis.
• Kissing balloon inflation after dilating SB was performed in fewer patients in NCB arm (p=0.001).
• Complete revascularisation was achieved in a similar proportion of patients in both arms.
• QFR post MV stenting was significant in side branch, which improved following treatment to side branch.
• Primary end point: Occurred in 49 patients in NCB group as compared with 28 patients in DCB group (Kaplan-Meier rate: 12.5% vs 7.2%; HR: 0.56;95% CI: 0.35-0.88; P= 0.013).
• Risk of spontaneous MI higher in NCB group (p=0.029) leading to a higher rate of target vessel MI in NCB group (p=0.009).
• No difference in secondary outcomes of al cause death, cardiac death, periprocedural MI, MACE without periprocedural MI, clinically driven TLR or stent thrombosis.

 

Limitations 

• Treatment allocation unblinded to the operators
• Results may not be applicable to sirolimus coated balloons.
• Overall low rates of patients presenting with myocardial infarction, so may not be able to extrapolate results to this group of patients
• Complex bifurcation lesions and those with calcium were excluded
• Overall comparable but low rates of intra coronary imaging use
• Lower rate of KBI in NCB group
• Females underrepresented.

 

Conclusions

• First randomised trail evaluating the use of DCBs for treating side branch stenoses following MV stenting in true bifurcation lesions.
• Combination of main vessel stenting and DCB treatment to the side branch led to fewer MACE at 12 months, driven by fewer target vessel myocardial infarctions.
• No difference in cardiac death, all cause death, or stent thrombosis were observed.
• Results consistent with smaller PEPCAD-V study.
• No reduction in target lesion revascularisation, suggesting the observed increase in myocardial infarctions may not have been deemed clinically significant to warrant re study or revascularisation.

  

 

The CLEAR trial: Colchcine in Acute Myocardial Infarction 

Rationale:

• There has been a lot on interest in anti-inflammatory therapeutics in coronary artery disease, given the role that inflammation is thought to have in the development of atherosclerosis. Given prior conflicting data, the aim of this study was to evaluate the effects of colchicine in patients following a myocardial infarction.

 

Publication:

• Jolly et al; CLEAR Investigators. Colchicine in Acute Myocardial Infarction. N Engl J Med. 2025 Feb 13;392(7):633-642.

 

Study Design

• International multicentre RCT
• Prospective
• Double blind
• 2 by 2 factorial design
• Patients randomly assigned to receive either colchicine or placebo and spironolactone or placebo in a 1:1:1:1 allocation. Results of the spironolactone arm are reported elsewhere.
• Randomisation stratified according to trial centre and type of myocardial infarction.
• Time to event analyses were performed

 

Trial Information

• 7062 patients enrolled (across 104 centres in 14 countries)
• 3528 patients assigned to receive colchicine, 3534 to receive placebo.
• Median follow up 3 years
• Mean age 61 years
• 20% females enrolled
• 9% had previous MI, 10% had prior PCI
• 5% had diabetes
• 1% presented with STEMI, 4.9% had NSTEMI
• C reactive protein levels and safety also assessed
• Trial drugs colchicine 0.5mg, spironolactone 25mg and placebo
• Initially weight-based dosage of colchicine, but swapped to once a day give higher than average discontinuation
• 9% of patients in colchicine group discontinued the trial regimen

 

Inclusion criteria:

• STEMI who underwent PCI or NSTEMI who had undergone PCI and had one or more of the following risk factors: an LVEF no more than 45%, diabetes mellitus, multi vessel coronary artery disease, prior MI or age greater than 60
• Patients enrolled within 72 hours of PCI

 

Selected exclusion criteria:

• Age ≤18years
• Pregnancy or breastfeeding
• Hypotension
• Diarrhoea
• Allergy to everolimus
• Unable to take DAPT

 

Primary Endpoint:

• Primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke or unplanned ischaemia driven coronary revascularisation.

 

Results:

• Primary outcome occurred in 9.1% of patients in colchicine group, as compared with 9.3% in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.16; P=0.93).
• There was no difference in death from cardiovascular causes, recurrent MI or stroke (hazard ratio, 0.98; 95% CI, 0.82 to 1.17)
• Death from non-cardiovascular causes occurred in 1.3% of patients in the colchicine group and 1.9% in the placebo group (hazard ratio, 0.68; 95% CI, 0.46 to 0.99)
• Primary outcome was consistent across all pre specified subgroups (age, sex, presence of diabetes, degree of coronary disease, renal function, presentation) aside from dosing. In those patients weighing less than 70kg who received BD dosing had fewer events.
• There was no difference in serious adverse events. More patients reported diarrhoea in the colchicine group (p<0.001). There was no difference in infections between groups.

 

Limitations 

• Women underrepresented.
• High rate of treatment discontinuation (in one quarter of patients in treatment arm)
• Twice daily colchicine was not evaluated.

 

Conclusions

• In patients presenting with STEMI or high risk NSTEMI, treatment with the anti-inflammatory colchicine did not reduce the incidence of death from cardiovascular causes, recurrent myocardial infarction, stroke or unplanned ischaemia-driven coronary revascularisation at a median of 3 years.
• There was no difference in secondary end points
• No difference in serious adverse events, however, increase in reported diarrhoea in colchicine arm
• These results contrast with the previous COLCOT trial, which enrolled 4745 patients within 30 days of AMI and compared colchicine with placebo. This trial demonstrated that colchicine reduced the primary outcome of a composite of death from CV causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularisation. More recent trials evaluating colchicine in patients post stroke have had similar neutral outcomes like this trial. Whilst it is unclear why there is a lack of consistency in results, the most recent trials have also been neutral.
• There is an ongoing need to assess therapeutics that impact different parts of the inflammatory pathways in large clinical trials.

 

NICOR publishes 2025 National Cardiac Audit Programme (NCAP) Annual Report

We are delighted to share with you the 2025 National Cardiac Audit Programme (NCAP) Annual Report, the annual summary report for patients, carers and the public and the 10 interactive clinical domain summary reports.

Covering the 12 months from 1 April 2023 to 31 March 2024, this year’s report provides evidence that the landscape of cardiovascular disease is evolving. There are clear examples of good practice across the NHS, however challenges and pressures persist – including in cardiovascular services. In some regions, waiting lists for elective cardiovascular treatments are growing longer, urgent admissions face delays, and care inequalities and variances remain a significant concern.

The NCAP analyses combined with inputs from clinical colleagues, patients, and carers, have provide accessible insights into the performance of cardiovascular services, highlighting both successes and areas where improvements can be made.

Thank all our colleagues, community representative group members and stakeholders for their continued support and contribution. Particularly our clinical colleagues, their supporting audit and clerical teams, and their hospital management teams for ensuring that important data are collected and sent to NICOR. We hope our annual reports put these data into context.

The annual report is accompanied by 10 interactive sub-specialty clinical reports that offer detailed, domain-level analyses. These interactive tools enable users to:

• drill down into the performance of different regions and individual hospitals
• focus on specific areas of interest to better understand local trends and outcomes.

These reports can be found on the NICOR website.

Understanding the continued pressures on hospitals and their clinical teams, we are most grateful for your continuing hard work and contributions to the NCAP.

We also invite you to contribute your comments, feedback, queries, or suggestions for future reports. Please NICOR: nicor.auditenquiries@nhs.net.

The introduction of Primary Percutaneous Coronary Intervention (PPCI) has seen a significant growth in the out of hours workload for interventional cardiologists. Very few medical specialties require the immediate return of senior medical staff to hospital on a 24/7 basis, where they are required to perform complex procedures in often very sick patients. This pattern of work is very disruptive to family life and involves regular sleep disturbance. Interventional cardiology risks becoming an unpopular specialty.

There is a perception that the time has come for a review of the working arrangements for consultant interventional cardiologists in the UK. The purpose of this document is to review the traditional arrangements and outline other options that are available under the current NHS consultant contract.

The introduction of Primary Percutaneous Coronary Intervention (PPCI) has seen a significant growth in the out of hours workload for interventional cardiologists. Very few medical specialties require the immediate return of senior medical staff to hospital on a 24/7 basis, where they are required to perform complex procedures in often very sick patients. This pattern of work is very disruptive to family life and involves regular sleep disturbance. Interventional cardiology risks becoming an unpopular specialty.

There is a perception that the time has come for a review of the working arrangements for consultant interventional cardiologists in the UK. The purpose of this document is to review the traditional arrangements and outline other options that are available under the current NHS consultant contract.

 

 

BCIS literature review

December 2024

Authors: Dr. Richard Jabbour, Dr. Claudia Cosgrove, Dr. Natalia Briceno

 

CORONARY ARTERY DISEASE

SENIOR-RITA trial

Invasive treatment in older adults with NSTEMI

 

Rationale: This study sought to determine whether a conservative approach, with medical therapy, or invasive coronary angiography with revascularisation was better in older patients (>75 years) presenting with NSTEMI.

 

Publication: Invasive Treatment Strategy for Older Patients with Myocardial Infarction. Kunadian et al. NEJM 2024 Nov 7;391(18):1673-1684.

 

Study design

• Multicentre (48 UK sites)
• Patients >75 years old presenting with NSTEMI
• Exclusions: STEMI, unstable angina, cardiogenic shock, life expectancy <1 year, deemed unable to undergo coronary angiography
• Randomised 1:1 (conservative management vs invasive management)
• Both arms received medical therapy including aspirin, P2Y12 inhibitor, statin, beta-blocker and ACE-inhibitor
• Primary outcome was a composite of death from cardiovascular causes or nonfatal myocardial infarction

 

Study population

• 1518 patients; mean age 82 years; 45% female
• 32% frail (Fried Frailty Index); 60% cognitive impairment (MoCA)
• Median follow up 4.1 years
• In Invasive arm: 90% underwent angiography, 50% received revascularisation (PCI in 47%, CABG in 3%)

 

Results

• Primary event occurred in 193 (25.6%) of invasive strategy arm, vs 201 (26.3%) of conservative arm (HR 0.94; 95% CI 0.77 to 1.14; P = 0.53).
• There was 25% relative reduction in the occurrence of non-fatal MI in the invasive group vs. the conservative group.
• There were fewer patients who underwent subsequent coronary angiography (5.6% vs. 24.2%) and revascularisation procedures (3.9% vs. 13.7%) in the invasive-strategy group than in the conservative-strategy group.
• In patients undergoing angiography: radial access in 89%;
• Procedural complications <1%
• TIA (2.4 % vs. 1.2%) and BARC bleeding (8.2% vs. 6.4%) in invasive strategy vs. conservative group.

 

Interpretation and clinical application

• Routine invasive angiography and revascularisation in addition to medical therapy, appears to offer no significant mortality benefit over medical therapy alone in patients older than 75 years presenting with NSTEMI.
• When invasive angiography was performed, in older, frail patients, rates of bleeding and procedural complications in this study were low.

 

Limitations

• Only 1 in 5 eligible patients were enrolled. 65% of patients excluded based on physician’s clinical decision underwent invasive procedure (likely clinician bias towards invasive management). However, in the screening log, patients randomised and those not randomised had similar baseline characteristics strengthening the generalisability of this study.

 

EARTH-STEMI meta-analysis

Complete revascularisation in older adults

 

Rationale: Current guidelines recommend complete revascularisation of non-culprit arteries in patients presenting with STEMI. However, older patients were underrepresented in the landmark trials on which these guidelines are based on. The aim of this meta-analysis was to evaluate whether complete revascularisation in older STEMI patients has a positive impact on long term clinical outcomes.

 

Publication reference: Campo et al. Complete Versus Culprit-Only Revascularization in Older Patients With ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis. Circulation. 2024 Nov 5;150(19):1508-1516.

 

Study Design

• Individual patient meta-analysis
• 7 randomised controlled trials included that compared complete revascularisation with culprit only (COMPLETE, Compare-Acute, CvLPRIT, DANAMI-3-PRIMULTI, FIRE, Full-REVASC, and a study by Hamza et al)
• Follow up ranged from 6 months to a maximum of 6.2 years.

 

Inclusion criteria:

• Age ≥ 75 years
• Clinical presentation as STEMI
• Successful treatment of culprit lesion
• Multivessel disease with at least one non-culprit lesion in a different vessel (angiographic or FFR guided)

 

Outcomes:

• Primary end point: composite of death, myocardial infarction or ischaemic driven complete revascularisation.
• Secondary end points: composite of cardiovascular death or myocardial infarction, individual components of composite outcomes. Safety endpoints including stroke, stent thrombosis, major bleeding and contrast induced kidney injury.

 

Trial Population:

• 1733 patients were included in this meta-analysis (917 in culprit only, 816 in complete group); Median age was 79 (77-83) years.
• 15% of patients in this study were older than 85 years of age.
• Baseline and procedural characteristics were similar, except for female sex (higher proportion of females in the culprit only group).
• 77% of the patients in the complete arm received PCI of non-culprit lesion within index hospitalization.
• Treatment of no culprit lesions physiology guided in 57%

Results:

• There was a numerically lower number of patients experiencing a primary outcome in the complete revascularisation group at the longest follow up, which did not reach statistical significance (HR 0.83, 95% CI 0.69-1.01).
• When censoring the follow up at each year, complete revascularisation demonstrated a significant reduction of the primary outcome at four years.
• Cardiovascular death or myocardial infarction was significantly lower in patients randomised to complete revascularisation at the longest follow up (HR 0.76, 95% CI 0.58-0.99).
• Ischaemia driven revascularisation was significantly lower in the complete revascularisation group.

 

Interpretation and clinical implications:

• Whilst there was a signal of benefit of the primary outcome at the longest follow up, this was only significant when follow up was censored to four years, suggesting that this early benefit may not be sustained at longer term follow up.
• Ischaemia driven revascularisation was lower in the complete group, but bias may have had an impact given the open label trials included.
• These results can be used to aid discussions with regards to management of older patients presenting with STEMI and multi-vessel disease.
• It is important to continue to assess each patient individually, balancing the pros and cons of complete revascularisation, taking into account frailty, co-morbidities and coronary artery disease complexity alongside procedural risk.

 

Limitations:

• Over 85’s underrepresented.
• Variation in length of follow up across studies included.
• Most trials included did not stratify the randomisation by age.
• Trials enrolled patients spanning a large time frame, with potential bias introduced with changes in techniques and device.

 

REC-CAGEFREE I

Drug coated balloons in native disease

 

Rationale: Drug coated balloons (DCB) are used in routine practice for both treatment of de novo small vessel coronary artery disease and in stent restenosis. However, it remains unclear whether the theoretical benefits of DCB translate into comparable clinical outcomes in larger coronary arteries. The aim of this trial was to assess the non-inferiority of DCB as compared with DES in non-complex de novo coronary artery disease regardless of vessel size in both acute coronary (including STEMI) and chronic coronary syndromes.

 

Publication reference: Gao et al. Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial. Lancet. 2024 Sep 14;404(10457):1040-1050.

 

Study Design

• 43 centres in China
• Randomized 1:1 (Swide DCB (paclitaxel and iopromide) versus Firebird 2 DES (sirolimus eluting DES with cobalt chromium alloy platform, 86 μm thick struts, durable polymer)
• Non-inferiority, open label
• Pre specified total length of follow up 10 years, 2 year follow up data presented
• Intention to treat analysis performed

 

Inclusion criteria:

• Patients aged 18 years or older
• Requiring PCI for acute or chronic coronary syndromes
• De novo non-complex target lesions regardless of vessel size
• Successful and satisfactory pre dilatation (no type D, E or F dissection, TIMI 3 flow, no residual stenosis greater than 30% or more, no serious complications)

 

Key Exclusion criteria:

•  Cardiogenic shock
•  Revascularisation for in stent restenosis

 

Outcomes:

• Primary end point: device orientated composite endpoint-DoCE (composite of cardiovascular death, target myocardial infarction (TV-MI) and clinically and physiologically indicated TLF at 24 months.
• Secondary end points were rates of DoCE at 1 month and 12 months, rates of individual components of DoCE, a patient orientated composite endpoint (all death, any stroke, any MI and any revascularisation) and individual components, target vessel failure, clinically and physiologically indicated target vessel revascularisation, BARC bleeding, device or vessel thrombosis.

 

Trial Population:

• 2902 potentially eligible, with 2272 undergoing successful predilatation and enrolment (78.3%)
• 106 out of 1133 randomised to the DCB group underwent rescue stenting (9.4%)
• 48.4% of cases enrolled involved small vessel disease (diameter  <3mm).
• Median age 62 years; 69.3% male; All patients of Chinese ethnicity
• 2529 lesions treated in the 2272 patients, of which 50.7% in the LAD
• 64.5% of lesions treated with cutting or scoring balloons, with no difference is use of these balloons between groups.
• Imaging performed in approximately one in ten patients.
• No signficant differences in baseline characteristics

 

Results:

• At 24 months, DoCE occurred in 6,4% of 1133 patients in DCB group and 3.4% of 1139 In the DES group, with a difference of 3.04% in cumulative event rate (P _{non-inferiority} =0.65), driven mainly by an increased rate of clinically or physiologically driven TLR.
• Peri procedural MI rates and major bleeding were similar in both groups.
• Vessel size exhibited a significant treatment by subgroup interaction, with a signal that DCB had greater benefit in reducing the primary outcome in small vessel coronary artery disease.

 

Interpretation and clinical implications:

• This is the first randomised study of DCB vs. DES in de novo coronary disease regardless of vessel size.
• In low complexity lesions regardless of vessel size, DES remains to DCB.
• In 1/5^th of patients, predilatation is unsuccessful requiring DES implantation
• For now, routine use of DCB should be limited to small vessel de novo disease and in stent re-stenosis.
• DES should remain the preferred treatment for de novo large vessel coronary artery disease.

 

Limitations:

• Single blinded open label, therefore could introduce bias in assessing outcomes.
• All patients of Chinese ethnicity, therefore results may not be translatable.
• Trial investigated a paclitaxel coated balloon, and therefore the results cannot be extrapolated to sirolimus coated balloons.

 

 

INTRVASCULAR IMAGING

OCCUPI

OCT-guided vs angiography-guided PCI in ‘complex’ lesions

 

Rationale: There is a growing body of evidence to suggest that intracoronary imaging guidance in PCI results in improved clinical outcomes, particularly in certain lesion subsets. However, the results of RCTs to date have been mixed. This study sought to determine the clinical benefits of OCT-guided vs angiography-guided PCI in ‘complex’ lesions.

 

Publication: Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea. Hong et al, Lancet, 2024 Sep 14;404(10457):1029-1039.

 

Study design

• Multicentre (20 sites in South Korea)
• Patients undergoing PCI with DES of ‘complex’ lesions*
• Randomised 1:1 (OCT vs. angio guidance)
• In OCT group: OCT performed pre-stent, and ‘recommended’ post stent.
• Open label.
• Primary outcome: MACE (cardiac death, MI, stent thrombosis, ischaemia-driven TLR) at 1 year

 

*Complex lesions defined as: acute MI, CTO, Long lesion (expected stent length ≥28 mm), Calcified lesions, Bifurcation, Unprotected LMS, Small vessel <2.5mm, Intracoronary thrombus visible on angiography, Stent thrombosis, In-stent restenosis, Bypass graft lesions

 

Study population

• 1604 patients
• 80% male, 20% female; Median age 64 years
• 33% with diabetes
• 99% patients completed 1 year follow up

 

Results

• Primary endpoint (MACE) occurred in 37 (5%) in the OCT arm and 59 (7%) in the angio arm. HR 0·62 (95% CI 0·41–0·93); p=0·023.
• Significantly lower rates of spontaneous MI (7 (1%) with OCT vs 19 (2%) with angio) and ischaemia-driven TVR (12 (2%) with OCT and 33 (4%) with angio.
• 545 (71%) of patients met all 3 criteria for ‘stent optimisation’.
• Patients with stent optimisation had significantly lower rates of the primary outcome (16 [3%] of 545 vs 19 [9%] of 222).
• Patients with suboptimal results on OCT had no significant difference in primary outcome compared to angiographic guidance.
• Stroke, bleeding, CIN not significantly different between groups.
• Procedural time greater by 10 min with OCT than angiographic guidance, (53 min vs. 43min).

Interpretation and clinical application

• In patients undergoing PCI with DES for a wide range of lesion subsets, OCT guidance, when used to achieve optimal mechanical stent results, is associated with a lower incidence of MACE at 1 year.
• No apparent detriment to using OCT in terms of procedural time or renal injury.

 

Limitations

• Relatively short follow up period for assessment of restenosis.
• Modest effect.

 

 

VALVULAR HEART DISEASE

NOTION 3 Trial

Role of PCI in patients with obstructive CAD undergoing TAVI

 

Rationale: The purpose of the trial was to analyse whether percutaneous coronary intervention (PCI) or conservative therapy was effective in patients in who had obstructive coronary artery disease underwent transcatheter aortic valve implantation (TAVI).

 

Publication date: NOTION-3. Lønborg J et al. PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med. 2024 Dec;391(23):2189-00.

 

Study Design

• International
• Randomized 1:1
• Parallel
• Open label

Patients with symptomatic severe aortic stenosis with obstructive coronary artery disease in at least one vessel were randomized to PCI (n = 227) vs. conservative therapy (n = 228).  PCI was ideally recommended to be performed prior to TAVI but was allowed during or within 2 days post TAVI.

 

Trial information:

• 455 Patients included.
• Duration of follow-up: median 2 years
• Mean patient age: 82 years
• Median STS 3%
• Percentage female: 32% (PCI) vs. 33% (conservative)
• Percentage with diabetes: 26% (PCI) vs 27% (Conservative)
• Median LVEF 60% (PCI) vs 60% (conservative)

 

Inclusion criteria:

• Symptomatic severe aortic stenosis assessed by Heart Team and selected for TAVI
• At least one vessel (≥2.5 mm) with obstructive coronary artery disease, defined as fractional flow reserve ≤0.80 or ≥90% angiographic stenosis

 

Exclusion criteria:

• Previous tissue AVR
• Limited life expectancy <1 year
• Severe renal failure – eGFR <20
• Recent acute coronary syndrome within 14 days
• Left main coronary artery stenosis

 

Characteristics:

• PCI prior to TAVI: 74%; PCI at the same time as TAVI: 17%; PCI post TAVI: 9%
• Balloon-expandable valve: 40%.
• Complete Revascularisation achieved 89%

Primary Endpoint: Major adverse cardiac events: a composite of all-cause mortality, myocardial infarction, or urgent revascularization

 

Principal Findings: The primary outcome was 26% in the PCI group vs. 36% in the conservative therapy group (p = 0.04).

 

Secondary outcomes:

• All-cause mortality: 23% (PCI) vs. 27% (conservative)
• MI: 7% (PCI) vs. 14% (conservative)
• Urgent revascularisation: 2% (PCI) vs. 11% (conservative)
• Major bleeding: 11% (PCI) vs. 10% (conservative)

 

Limitations

• Small sample size and therefore underpowered for hard end points
• Patients with recent ACS and left main disease excluded
• Unblinded outcome may have influenced unplanned revascularisation
• Patients with a recent acute coronary syndrome and left main coronary-artery stenosis were not included
• The enrolment period occurred over the course of 5 years during which the technical aspects of TAVI and PCI, and the medical treatment as well as patient selection for TAVI evolved.

 

Conclusions

• The trial found that in patients with obstructive coronary artery disease undergoing TAVI, there was a reduction in major adverse cardiovascular events in those who underwent PCI prior or around the time of the TAVI procedure driven by a reduction in myocardial infarction and urgent revascularisation.
• This contrasts with the ACTIVATION trial which did not find a net benefit and was halted early due to futility. NOTION 3 included more patients and had a longer follow-up.
• The ongoing COMPLETE TAVR trial is also assessing this hypothesis.
• The decision to perform PCI prior to TAVI should consider the disease complexity, coronary artery location, age, patient comorbidities and symptoms. This should also be balanced with the patient’s bleeding risk.

 

Limitations:

• It should be noted that the median number of physiologically significant lesions per patient was low (n=1), the SYNTAX score was also low (median 9), and few patients therefore had multivessel disease.

 

RESHAPE HF 2 Trial

Mitral edge-edge repair in moderate to severe MR and heart failure

 

Rationale: To assess the safety and efficacy of mitral edge-to-edge repair (MitraClip System) with optimal medical therapy in symptomatic heart failure (NYHA class II- IV) patients with co-existent secondary moderate to severe mitral regurgitation. Registry data has indicated that a relatively high proportion of patients undergoing TEER contemporarily actually have moderate rather than severe HR (44% moderate from registry data). Accordingly, the RESHAPE-HF2 trial assessed moderate to severe MR and the effectiveness of TEER on top of optimal medical therapy (OMT).

 

Publication date: Anker SD, et al. Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation. N Engl J Med. 2024 Nov 14;391(19):1799-1809.

 

Study Design

• International (30 sites, 9 countries)
• Randomised 1:1 TEER + OMT vs OMT alone
• Parallel assignment; Open label

 

Patients with HF and grade 3-4 MR who remained symptomatic despite optimal medical therapy were randomized to M-TEER with MitraClip + OMT (n=250) vs. OMT alone (n=255).

 

Trial Information

• Total number of patients: 505 (250 patients device group; 255 control)
• Duration of follow-up: 24 months (mean 18.8 months)

 

Inclusion criteria:

• Signs and symptoms of HF (NYHA class II-IV) despite optimal medical therapy.
• Left ventricular ejection fraction (LVEF) of 20-50%.
• Moderate-to-severe (3+) or severe (4+) secondary (functional) MR.
• Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization.

 

Exclusion criteria:

• Predominantly degenerative MR (primary).
• Mitral surgery recommended as preferred treatment option.
• Renal replacement therapy.
• Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.

 

Baseline Characteristics

• Prior myocardial infarction: 57.6% device group vs. 52.9% control group
• Prior PCI: 47.2% device vs. 49.0% control
• Prior coronary artery bypass grafting (CABG): 27.6% device vs. 25.1% control
• Ischemic HF: 64.8% device vs. 65.5% control
• HF hospitalization within 1 year: 66% device vs. 65.9% control
• Median NT-proBNP: 2651 device vs. 2816 control
• Median EF 32% device group vs. 31% control

 

Primary Outcome measures:

• Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death within 24 months.
• Rate of total (first and recurrent) HF hospitalizations within 24 months.
• Change in quality of life (overall KCCQ-OS score) from baseline to 12 months.

 

Principal Findings:

• The primary endpoint: MitraClip + OMT vs. OMT, was 37.0 vs. 58.9 events per 100 patient-years (p = 0.002).
• First or recurrent HF hospitalization: 26.9 vs. 46.6 events per 100 patient-years (p = 0.002).
• Mean change from baseline in KCCQ-OS: 21.6±9 (TEER+OMT) vs. 8± 24.5 (OMT) (p < 0.001).
• MR ≤2+ at 12 months: 90.4% (TEER + OMT) vs. 36.1% (OMT) (p < 0.001).

 

Conclusion:

• MitraClip therapy on top of OMT was found to be beneficial and trial met the composite primary endpoint of first / recurrent HF hospitalisation and all-cause mortality at 24 months.
• The benefit was primarily due to a reduction in HF hospitalization since there was no reduction in all-cause death observed.
• TEER was associated with greater improvements in QoL score (KCCQ-OS).

 

Limitations:

• Unblinded nature may have introduced bias, especially regarding QoL assessments