R&D Literature Review Jan 2019

BCIS R&D Group

 

Literature Review January 2019

 

Prepared by: Michael Mahmoudi & Vijay Kunadian

Edited by Nick Curzen

 

 

CORONARY PHYSIOLOGY

 

Consistent message at 5 years from FAME 2… improved outcome by virtue of less revasc in the PCI+OMT group compared to OMT alone (but death & MI rate no different)

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve

NEJM   2018; 379:250-59

The FAME-2 study has shown better 1-year clinical outcomes in patients undergoing FFR-guided PCI plus optimal medical therapy (OMT) versus OMT alone. The current manuscript provides 5-year outcomes of the study. FAME-2 had randomised 888 patients with angiographically significant coronary artery disease in whom at least one lesion was hemodynamically significant (FFR ≤ 0.80) to either FFR guided PCI plus OMT (n=447) or OMT alone (n=441). At 5 years, the PCI groups had a lower rate of the primary endpoint (a composite of death, MI, or urgent revascularization) (13.9% vs. 27%; HR 0.46; 95% CI 0.34-0.63; p<0.001). This difference was driven by a reduction in the rate of ravscularization in the PCI group (6.3% vs. 21.1%; HR 0.27; 95% CI 0.18-0.41; p=0.41). The rates of death (5.1% vs. 5.2%; HR 0.98; 95% CI 0.55-1.75) or MI (8.1% vs. 12%; HR 0.66; 95% CI 0.43-1.0) were similar in the PCI and OMT groups.

 

No significant difference in performance or drift for  SJM/Abbott or Comet BSC pressure wires in simultaneous measurements

A Randomised Controlled Trial to Compare two Coronary Pressure Wires using Simultaneous Measurements in Human Coronary Arteries The COMET trial.

EuroIntervention. 2018 Oct 30. pii: EIJ-D-18-00786. doi: 10.4244/EIJ-D-18-00786.

There is much discussion about the relative performance of pressure wires, both in terms of their diagnostic accuracy but also how much drift they exhibit. This study examined the relative performance of the new COMETÔ wire from Boston Scientific (BS), and the established technology from St Jude/Abbott Vascular (SJ), using a simultaneous readings from pairs of wires. Patients were randomised to one of three groups, BS/BS; SJ/SJ; SJ/BS. After pressure equalisation at the guide catheter, we recorded paired observations in sequence: (a) distal to proximal pressure ratio at baseline; (b) FFR at maximum hyperaemia; (c) pressure on withdrawal into the guide catheter to quantify “drift”. 106 patients were randomised, yielding 288 sets of paired recordings (BS/BS = 90; SJ/SJ = 90; SJ/BS = 108). Drift was recorded from 208 vessels (BS = 105; SJ = 103). The mean (±SD) differences for the randomised pairs were similar: BS/BS = 0.0016 (0.023); SJ/SJ = 0.002 (0.03); SJ/BS = 0.0013 (0.028). The primary outcome tested the hypothesis that the absolute magnitude of the difference (irrespective of sign) observed in the SJ/BS pairing would be similar to that in the SJ/SJ group. The median (IQR) values were SJ/BS = 0.015 (0.01-0.03); SJ/SJ = 0.01 (0.00-0.03); P = 0.61. The drift, expressed as the median (IQR) difference in Pd/Pa from 1.0 (irrespective of sign), was similar: BS = 0.02 (0.01-0.05); SJ = 0.02 (0.01-0.04); P = 0.14. There was no significant difference between these wires in terms of safety and performance, including the degree of drift.

 

 

Insights into the future…. Using physiology and virtual PCI model to predict outcome in serial or diffuse disease

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease. Primary Results of the International Multicenter iFR GRADIENT Registry.

JACC Cardiovasc Intv 2018; 11:757-67

Physiological assessment of serial stenoses or diffuse vessel disease may be challenging using conventional FFR. Because of the stability of resting coronary flow across a wide range of lesion severity, in tandem or diffuse disease, iFR interrogation of each lesion is theoretically permissible. iFR pullback recording may thus theoretically allow construction of a physiological map of lesion severity and thereby perhaps to predict the physiological outcome after modelling a virtual PCI. The iFR GRADIENT registry examined the accuracy of online-generated iFR-pullback curves to predict physiological outcomes post PCI and to assess the impact of these data on procedural decision-making in 123 patients undergoing PCI. Vessels protected by a graft conduit, patients with STEMI, TIMI flow grade <3, presence of clot, or lesion severity >90% by visual assessment were excluded.  The predicted post-PCI iFR calculated online was 0.93±0.05; the actual iFR was 0.92±0.06. iFR pullback predicted the post-PCI iFR with 1.4±0.5% error. As compared to angiography-guided decision-making, after iFR pullback, decision-making was changed in 31% of vessels.

 

 

Insights into the future… physiology in all coronaries calculated from your angiogram:  all the benefits of pressure wiring all vessels at the diagnostic stage, without the pressure wire?

Diagnostic performance of angiography-derived fractional flow reserve: a systematic review and Bayesian meta-analysis 

European Heart Journal, Volume 39, Issue 35, 14 September 2018, 3314–3321

Collet and colleagues sought to evaluate the diagnostic performance of FFR derived from angiography in diagnosing hemodynamically significant coronary artery disease. They undertook a systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR in 13 studies and 1842 vessels. The primary outcome was pooled sensitivity and specificity. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89%, specificity of 90% (95% credible interval 88–92%), positive likelihood ratio (+LR) of 9.3 and negative likelihood ratio (−LR) of 0.13. The summary area under the receiver-operating curve was 0.84. The authors concluded that FFR derived from angiography was good to detect hemodynamically significant lesions compared with invasive FFR as reference. Further studies are required evaluating clinical endpoints using this technique.

 

RENAL DENERVATION

 

Renal denervation… hanging on in there & maybe ready for a come back?

Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial.

The Lancet 2018; 391:2335-45

The role of renal denervation in the treatment of hypertension has been controversial. The RADIANCE-HTN SOLO study was a multicentre, international, single-blind, randomised, sham-controlled trial undertaken in 21 US and 18 European centres. Patients were deemed eligible if they had ambulatory BP ≥ 135/85 mmHg and < 170/105 mmHg after a 4-week discontinuation of up to two antihypertensive medications. The primary efficacy endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. The study screened 803 patients and 146 eligible patients were randomised to either endovascular renal denervation (n=74) or a sham procedure (n=72). Renal denervation was associated with a greater reduction in daytime ambulatory systolic BP -8.5 mmHg vs. -2.2 mmHg; baseline adjusted difference between the groups: -6.3 mmHg; 95% CI -9.4 to -3.1; p=0.0001). No major adverse events were observed in the two groups.

Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. The

Lancet 2018; 391:2346-55

The SPYRAL HTN-ON MED study examined the safety and BP response of renal denervation in patients with uncontrolled hypertension on antihypertensive medications with regular drug adherence testing. Eligible patients had office systolic BP of between 150 mmHg-180 mmHg and diastolic BP of ≥ 90 mmHg, a 24 hour ambulatory systolic BP of between 140 mmHg-170 mmHg at a second screening and were on 1-3 antihypertensive medications. The primary efficacy endpoint was BP change from baseline based upon ambulatory BP measurements at 6 months. The study screened and enrolled 467 patients over a period of 2 years.  The results of the first 80 patients (renal denervation=38; sham control=42) are presented in this publication. Office and 24 hour ambulatory BP was lower in the denervation group (mean baseline adjusted treatment differences in 24 hour systolic BP -7.0 mmHg; 95% CI -12 to -2.1; p=0.0059; 24 hour diastolic BP -4.3 mmHg; 95% CI -7.8 to -0.8; p=0.0174; office systolic BP -4.2 mmHg; 95% CI -12.4 to -0.7; p=0.025, and office diastolic BP -4.2 mmHg; 95% CI -7.7 to -0.7; p=0.019). At 6 months, renal denervation was associated with greater reductions in office systolic BP (difference -6.8 mmHg; 95% CI -12.5 to -1.1; p=0.02), 24 hour systolic BP (difference -7.4 mmHg; 95% CI -12.5 to -2.3; p=0.005), office diastolic BP (difference -3.5 mmHg; 95% CI  -7-0; p=0.048) and 24 hour diastolic BP (difference -4.1 mmHg; 95% CI  -7.8 to -0.4; p=0.29). Medication adherence was approximately 60%. There were no major adverse events in either group.

 

ANTIPLATELET THERAPY

 

 

First trial of ticagrelor monotherapy after DES does not show benefit compared with conventional DAPT and aspirin

Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs. aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of drug-eluting stent: a multicentre, open-label, randomised superiority trial.

The Lancet 2018; 392:15-21

The optimal combination and duration of antiplatelet therapy in patients treated with DES remains uncertain. The GLOBAL LEADERS trial was designed to compare the benefits and risks of 2 years of treatment with 90mg ticagrelor twice daily (in combination with aspirin for the first month) with conventional 1-year dual antiplatelet therapy (DAPT) followed by aspirin alone in patients treated exclusively with a biolimus A9-eluting stent. The study randomised 15,968 patients with stable angina or ACS to receive either (a) aspirin 75-100mg daily plus ticagrelor 90mg twice daily for 1 month followed by 23 months of ticagrelor monotherapy or (b) standard DAPT with aspirin 75-100mg daily plus clopidogrel 75mg daily (for patients with stable angina), or ticagrelor 90mg twice daily (for ACS patients) for 12 months followed by aspirin alone for a further 12 months. The primary endpoint at 2 years was a composite of all-cause mortality or new Q-wave MI. Key secondary safety endpoints were BARC grade 3-5 bleeding. At 2 years, the primary endpoint was similar in the ticagrelor and aspirin arms (3.81% vs. 4.37%; RR 0.87; 95% CI 0.75-1.01; p=0.073). BARC grade 3-5 bleeding was also similar in the two groups (2.04% vs. 2.12%; RR 0.97; 95% CI 0.78-1.20; p=0.77).

 

The intuitive feeling that earlier potent P2Y12 inhibitor should reduce events in PPCI is still not endorsed by data!

No Benefit of Ticagrelor Pretreatment Compared With Treatment During Percutaneous Coronary Intervention in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Circ Cardiovasc Interv 2018; 11:e005528

The potential for ticagrelor preloading to provide any additional benefits in STEMI patients receiving the drug in the cath lab is controversial. Data from the SWEDEHEART registry, including 7433 patients of whom 5438 patients had received ticagrelor pretreatment prior to PPCI, has been used to study whether such an approach is associated with reductions in the composite endpoint of all-cause mortality, MI, and stent thrombosis at 30-day follow-up. In this study, crude event rates showed no difference in 30-day composite endpoint (6.2% vs. 6.5%; p=0.69), mortality (4.5% vs. 4.7%; p=0.86), MI (1.6% vs. 1.7%; p=0.72) or stent thrombosis (0.5% vs. 0.4%; p=0.80). Ticagrelor pretreatment did not increase the rate of in-hospital major bleeding rates.

 

 

Ideal duration of DAPT after ACS PCI with DES… yes, it’s still as clear as mud!

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial.

The Lancet 2018; 391:1274-84

The debate regarding the optimal duration of dual antiplatelet therapy (DAPT) following implantation of a DES in patients presenting with an ACS remains unresolved. The SMART-DATE study was a randomised, open-label, non-inferiority trial at 31 South Korean centres that compared a strategy of either 6-month (n=1357) or 12-month or longer DAPT (n=1355) in patients presenting with unstable angina, NSTEMI, or STEMI. The primary endpoint was a composite of all-cause mortality, MI, or stroke at 18 months. Secondary endpoints included individual components of the primary endpoint, definite or probable stent thrombosis and BARC type 2-5 bleeding at 18 months. The median duration of DAPT was 6.1 months in the 6-month group and 17.7 months in the 12-month or longer group. The primary endpoint occurred 63 patients in the 6-month DAPT group and 56 patients in the 12-month or longer group (cumulative event rate 4.7% vs. 4.2%; absolute risk difference 0.5%; upper limit of one-sided 95% CI 1.8%; pnon-inferiority=0.03). The rates of all-cause mortality (2.6% vs. 2.9%; p=0.90), stroke 0.8% vs. 0.9%; p=0.84), stent thrombosis (1.1% vs. 0.7%; p=0.32), and bleeding (2.7% vs. 3.9%; p=0.09) were similar in both groups. MI was more common in the 6-month group (1.8% vs. 0.8%; p=0.02). Based upon the increased risk of MI and the wide non-inferiority margin, the study has recommends prolonged DAPT in ACS patients undergoing PCI with DES.

 

De-escalating from prasugrel to clopidogrel guided by platelet function testing in ACS PCI patient <70 improves outcome… but not in the older age group

Age and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: results from the randomized TROPICAL-ACS trial 

European Heart Journal, Volume 39, Issue 29, 1 August 2018, 2749–2758,

Our population is ageing with consequent increase in cardiovascular disease burden and co-morbidities. Often strategies that work in younger patients have not been proven to be beneficial in older patients. The older patients are often classified as high bleeding risk patients and therefore a gentler approach to antiplatelet therapy post PCI might be an attractive strategy. To prove this, the authors of the above trial studied the impact of age on clinical outcomes following de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Patients were randomly assigned in a 1:1 fashion to either standard treatment with prasugrel for 12 months (control group) or to a guided de-escalation regimen (1 week prasugrel followed by 1 week clopidogrel and platelet function testing guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). In younger patients (age ≤70 years, n = 2240), the occurrence of cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to the BARC criteria at 1 year was significantly lower in guided de-escalation vs. control group [5.9% vs. 8.3%; P = 0.03]. In elderly patients (age >70 years, n = 370), the absolute risk of events was higher without significant differences between guided de-escalation vs. control group (15.5% vs. 13.6%; P = 0.56). The authors concluded that the treatment effects of guided de-escalation for P2Y12 inhibitors is different between young and elderly patients. The net clinical benefit seen in younger patients was not seen in older patients. This study of course is limited by small sample size and will need to be evaluated further in larger studies.

 

STRUCTURAL/VALVE INTERVENTION

 

 

A new low frequency worm of concern about coronary obstruction after TAVI?

Delayed Coronary Obstruction After Transcatheter Aortic Valve Replacement.

JACC 2018; 71:1513-24

The incidence and outcome of delayed coronary obstruction (DCO) following TAVI are unknown. Retrospective data analysis from an international multicentre registry, including 17,092 patients, has demonstrated that DCO has an incidence of 0.22%, and commonly occurred between 1-7 days after the procedure. DCO was more common after valve-in-valve implantation (0.89% vs. 0.18%; p<0.001) and with self-expandable valves (0.36% vs. 0.11% (balloon expandable); p<0.001). The most common presentation was with cardiac arrest (31.6%) followed by STEMI (23.7%), with PCI being the most common treatment strategy. The left coronary artery was obstructed in 92.1% of cases. The in-hospital death rate was 50%, and was greater if DCO occurred within 7 days of the procedure.

 

 

Local anaesthetic for TF TAVI is quicker with shorter hospital stay with no cost in terms of outcome…. Going, going, GONE!

Comparison of general anaesthesia and non-general anaesthesia approach in transfemoral transcatheter aortic valve implantation

Heart 2018. Oct;104(19):1621-1628.

In the UK TAVI registry, the authors studied the impact of GA versus LA on procedural outcomes and 30-day and 1-year mortality in TF TAVI procedures using either an Edwards Sapien or a Medtronic CoreValve prosthesis. Propensity score-matching analysis was performed to adjust for confounding factors. 2243 patients were studied (aged 81.4±7.5 years, 1195 males). 81% underwent TAVI with GA and 19% without GA. Transoesophageal echocardiography (TOE) was used in 92.3% of GA and 12.4% of non-GA cases (p<0.001). There was no significant difference in the rate of successful valve deployment (GA 97.2% vs non-GA 95.7%, p=0.104) and in the incidence of more than mild aortic regurgitation at the end of the procedure (GA 5.6% vs non-GA 7.0%, p=0.295). Procedure time was longer (131±60 vs 121±60mins, p=0.002) and length of stay was greater (8.0±13.5 vs 5.7±5.5 days, p<0.001) for GA cases with no difference in 30-day and 1-year mortality rates did not differ between the groups. The authors concluded that procedure outcome, and 30-day and 1-year mortality are not influenced by mode of anaesthesia albeit GA was associated with longer procedure duration and greater length of stay.

 

Promising results for balloon expandable mitral valve… would be really interesting to see the outcome in lower risk patients?

Clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation: a 7-year experience

European Heart Journal, Volume 39, Issue 28, 21 July 2018, 2679–2689,

Percutaneous approaches to treat mitral valve disease are the subject of much interest and research. In this study, the authors evaluated the early and long-term clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation (TMVI). Patients were followed at 1 month, 1 year, and yearly thereafter. A total of 91 patients (median age 73; 70% female) at high risk for surgery with a median EuroSCORE II of 9.6 (4.0–14.6)% underwent TMVI. Indication for TMVI was bioprosthesis failure (valve-in-valve) in 37.3%, annuloplasty failure (valve-in-ring) in 33.0%, and severe mitral annulus calcification (MAC) in 29.7%. The transseptal approach was used in 92.3% of patients with technical success of 84.6% of patients and the mean transmitral gradient decreased from 9.3 ± 3.9 mmHg at baseline to 6.0 ± 2.3 mmHg at discharge (P < 0.001). At 30 days, 7.7% of patients had died, without significant differences between groups, and a major stroke occurred in 2.2% of patients. The cumulative rates of all-cause mortality at 1-year and 2-year follow-up were 21.0% and 35.7%, with a higher late mortality in patients with annular calcification. At 6 months to 1 year, 68.9% of patients were in NYHA Class I/II, and 90.7% of patients had mild or less mitral regurgitation. The authors concluded that transcatheter mitral valve implantation using balloon-expandable valves in selected patients was associated with a low rate of peri-procedural complications and acceptable long-term outcomes.

 

MULTIVESSEL DISEASE/ PCI v CABG

 

Is PCI really equivalent to CABG in complex MV disease?

Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.

The Lancet 2018; 391:939-48

The mortality benefit of CABG over PCI remains debatable. The authors have undertaken a meta-analysis of 11 randomised studies, including 11,518 patients assigned to PCI (n=5,753) or CABG (5,765) with multivessel or left main disease who did not present with acute MI and who had more than 1-year follow-up for all-cause mortality. PCI was undertaken with BMS or DES. Mean SYNTAX score was 26, with 22.1% of patients having a SYNTAX score of ≥33. As compared to CABG, PCI was associated with greater 5-year all-cause mortality (11.2% vs. 9.2%; HR 1.20; 95% CI 1.06-1.37; p=0.0038). Further breakdown of the data has indicated that 5-year all cause mortality was significantly greater with PCI in patients with multivessel disease (11.5% vs. 8.9%; HR 1.28; 95% CI 1.09-1.49; p=0.0019) including those with diabetes (15.5% vs. 10%; HR 1.48; 95% CI 1.19-1.84; p=0.0004). In patients with left main disease, 5-year all-cause mortality was similar with PCI and CABG regardless of the diabetic status and SYNTAX score (10.7% vs. 10.5%; HR 1.07; 95% CI 0.87-1.33; p=0.52).

 

Multivessel PCI can be equally successful if either done in a single session or staged

Single-session versus staged procedures for elective multivessel percutaneous coronary intervention

Heart 2018 Jun;104(11):936-944

Toyoto et al studied the effect of single-session multivessel percutaneous coronary intervention (PCI) strategy versus staged multivessel strategy on clinical outcomes in patients with stable coronary artery disease or NSTEMI in the Kyoto PCI/CABG cohort 2 registry in 2018 patients. All-cause death, myocardial infarction and stroke at 5-year follow-up were the primary outcome. 35% patients underwent single-session multivessel PCI and 65% had staged multivessel PCI. Though the 30-day incidence of all-cause death was significantly higher in the single-session group than in the staged group (1.1% vs. 0.2%, p=0.009), the causes of death in 11 patients who died within 30 days were generally not related to the procedural complications. The 5-year primary outcome was not different between the 2 groups (p=0.45). For the subgroup analyses including age, gender, extent of CAD, severe chronic kidney disease and heart failure, there was no significant interaction between the subgroup factors and the effect of the single-session strategy versus the staged strategy for the primary outcome measure. The authors concluded that single-session multivessel PCI strategy was associated with at least comparable 5-year clinical outcomes compared with the staged multivessel PCI.

 

Useful to know, but rocket science this ain’t

Prior Percutaneous Coronary Intervention and Mortality in Patients Undergoing Surgical Myocardial Revascularization. Results From the E-CABG (European Multicenter Study on Coronary Artery Bypass Grafting) With a Systematic Review and Meta-Analysis.

Circ Cardiol Intv 2018; 11:e005650

The clinical implications of PCI in patients who subsequently require CABG are uncertain. Data from the prospective European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) including 3641 patients of whom 685 patients had previously undergone PCI has shown that prior PCI was not associated with increased hospital mortality (OR 0.90; 95% CI 0.39-2.08; p=0.81). Prior PCI was not shown to have any impact upon hospital morbidity and mortality, blood transfusions, hospital resource use, or neurological/renal/cardiac complications.

 

MISCALLANEOUS

 

Reassurance from UK dataset that left radial approach is at least as safe as right radial…. Or perhaps even safer??

Incidence, Determinants, and Outcomes of Left and Right Radial Access Use in Patients Undergoing Percutaneous Coronary Intervention in the United Kingdom. A National Perspective Using the BCIS Dataset.

JACC Cardiovasc Intv 2018; 11:1021-33

The right radial route (RRR) has become the most common route for coronary intervention in many European countries. The left radial route (LRR) is occasionally used in patients with previous CABG as well as patients in whom anatomical considerations preclude the use of the RRA. Data from the BCIS database has been used to compare RRR and LRR with regards to in-hospital or 30-day mortality, MACE, in-hospital stroke, and major bleeding complications between 2007-2014. The study included 342,806 cases with 96% in the RRA group and 4% in the LRR group. As compared to the RRR, the LRR was not associated with significant differences in in-hospital mortality (OR 1.19; 95% CI 0.90-1.57; p=0.20), 30-day mortality (OR 1.17; 95% CI 0.93-1.74; p=0.16), MACE (OR 1.06; 95% CI 0.86-1.32; p=0.56) or major bleeding (OR 1.22; 95% CI 0.87-1.77; p=0.24). In propensity match analysis, LRR was associated with a significant decrease in in-hospital stroke (OR 0.52; 95% CI 0.37-0.82; p=0.005).

 

Drug-coated balloons in de novo lesions in small vessels… another niche?

Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an open-label randomised non-inferiority trial.

The Lancet 2018; 392:849-56

Drug-eluting balloons (DEB) have emerged as a realistic treatment strategy for in-stent restenosis but their role in the treatment of de novo CAD remains controversial. The BASKET-SMALL 2 trial examined the non-inferiority of DEB (SeQuent Please, B Braun Melsungen AG, Germany) versus the everolimus-eluting Xience stent in 758 patients (DEB=382, Xience=376) with de novo lesions < 3mm in diameter. Patients included those with ACS, stable angina, or evidence of silent ischemia. The primary endpoint was the non-inferiority of DEB versus Xience with regards to MACE as defined by cardiac death, non-fatal MI, and TVR after 12 months. The non-inferiority margin was set as an absolute difference of 4% in MACE. Non-inferiority was demonstrated as the 95% CI of the absolute difference was below the predefined margin (-3.83 to 3.93%; p=0.022). At 12 months, the DEB and Xience groups had similar MACE rates in the full analysis population (7.5% vs. 7.3%; HR 0.97; 95% CI 0.58-1.64; p=0.92).

 

Does  a biodegradable polymer really make any difference at all in DES?  Another study shows no harm or benefit?

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable polymer coronary stent (TARGET ALL Comers): a multicentre, open-label, randomised non-inferiority trial.

The Lancet 2018; 392:1117-26

The biodegradable polymer concept, although attractive in theory, has remained an enigma in the field of PCI. The TARGET ALL Comers study was a multicentre, open-label, randomised non-inferiority trial comparing the FIREHAWK DES (n=823) with its fully biodegradable sirolimus-containing polymer versus the Xience DES (n=830). The primary endpoint was target lesion failure (TLF) at 12 months, defined as a composite of cardiac death, target vessel MI< or ischemia driven TLR. Late lumen loss was the primary endpoint of an angiographic substudy. At 12 months, TLF was 6.1% in the FIREHAWK group and 5.9% in the Xience group (difference 0.2%; 90% CI -1.9 2.2; pnon-inferiority=0.004; 95% CI -2.2 to 2.6; psuperiority =0.88). The rates of stent thrombosis and ischemia driven revascularization were similar in the two groups. Late lumen loss in the angiographic substudy were also favourable (0.17mm for FIREHAWK vs. 0.11mm for Xienec; p=0.48; absolute difference 0.05 mm; 95% CI -0.09 to 0.18; pnon-inferiority=0.024).

No prognostic benefit to CTO PCI in patients presenting with STEMI… but ultimately less angina.  Shouldn’t we leave the CTO alone  and then wait to see who develops angina, then?

Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction.

Heart 2018 Sep;104(17):1432-1438

To treat or not to treat a CTO in the setting of a STEMI is a common clinical conundrum given concurrent CTO is found in 10% of patients with STEMI. The authors determined mid-term and long-term clinical outcome of CTO-PCI versus CTO-No PCI in 302 STEMI patients after successful primary PCI. Patients were randomised to either CTO-PCI or CTO-No PCI. Cardiac death, coronary artery bypass grafting and MI consisted of the primary outcome (MACE). Other end points were 1-year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic volume and angina status. At a median follow-up of 3.9 years MACE was not significantly different between arms (13.5% vs. 12.3%, P=0.93). Cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality (12.9% vs. 6.2%, HR 2.07, P=0.11). One-year LVF did not differ between both arms. However, there were more patients with freedom of angina in the CTO-PCI arm at 1 year (94% vs. 87%, P=0.03). In this randomised trial involving STEMI patients with a concurrent CTO, CTO-PCI was not associated with a reduction in long-term MACE compared to CTO-No PCI albeit with more patients free of angina in the CTO-PCI group.

 

A more sinister side to a condition we are now a bit blasé about?   Takotsubo bites back

Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy.

Circulation  2018; 137:1039-1048

Despite normalization of the resting LV ejection fraction following an episode of Takotsubo cardiomyopathy (TCM), the long-term manifestations of this clinical entity has been poorly investigated. An observational case-control study of 37 patients with prior (range 13-39 months) TCM and 37 age- & gender-matched controls has examined long-term clinical and functional consequences of TCM using serum biomarkers, cardiopulmonary exercise testing, echocardiography, and CMR including 31P-spectroscopy.  In this study 97% of participants were female, 88% had symptoms compatible with heart failure and limitation on exercise testing (reduced peak oxygen consumption 24±1.3 vs. 31±1.3 ml/Kg/min, p<0.001; increased VE/VCO2 slope 31±1 vs. 26±1; p=0.002). Furthermore, TCM patients had impaired cardiac deformation indices (apical circumferential strain -16±1 vs. -23±1.5%; p<0.001; global longitudinal strain -17±1 vs. -20±1%; p=0.006), increased T1 mapping values (1264±10 vs. 1184±10 ms; P<0.001) and impaired cardiac energetic status (phosphocreatine:∂-adenosine triphosphate ratio 1.3±0.1 vs. 1.9±0.1; p<0.001).

 

Fascinating insight into the potential benefit of CTCA as the front line test for stable chest pain….  FORECAST looms!

The SCOT-HEART Investigators. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

NEJM 2018; 379:924-33

The long-term clinical impact of CT coronary angiography (CTCA) in the assessment of patients with stable chest pain is uncertain. The SCOT-HEART investigators examined the rates of death from coronary artery disease or non-fatal MI at 5-years in 4146 patients with stable chest pain who had been referred to a cardiology clinic for further evaluation and who were randomized to either CTCA plus standard care (n=2073) or standard care alone (n=2073). The 5-year rate of the primary endpoint was significantly lower in the CTCA group (2.3% vs. 3.9%; HR 0.59; 95% CI 0.41-0.84; p=0.004), driven by a lower rate of nonfatal MI in the CTCA group (HR 0.60; 95% CI 0.41-0.87). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTCA group in the first few months of follow-up, the overall rates were similar in the two groups (HR 1.0; 95% CI 0.88-1.13 for invasive angiography and HR 1.40; 95% CI 1.19-1.65 for revascularization). The observed results may in part be explained by the CTCA group having more preventive therapies (odds ratio 1.40; 95% CI1.19-1.65) and more antianginal therapy (odds ratio 1.27; 95% CI 1.05-1.54).

 

The final nail in the coffin for for aspirin as a primary prevention treatment in patients without CV disease?

Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.

NEJM  2018 Online

The role of aspirin in primary prevention has remained controversial particularly given the increased risk of bleeding. The ASPREE trial randomized 19,114 men and women aged 70 years or older (≥65 years amongst blacks and Hispanics in the US) to receive either aspirin 100mg/day (n-9525) or placebo (n=9589). Participants did not have any evidence of cardiovascular disease, dementia, or disability. The prespecified secondary endpoint reported in this publication included major haemorrhage, and cardiovascular disease defined as fatal coronary heart disease, non-fatal MI, fatal or nonfatal stroke, or hospitalization for heart failure. After a median of 4.7 years follow-up, both the aspirin and placebo group had similar rates of cardiovascular disease (10.7 vs. 11.3 events per 1000 person-years; HR 0.95; 95% CI 0.83-1.08). Aspirin was associated with greater rates of major haemorrhage (8.6 vs. 6.2 events per 1000 person-years; HR 1.38; 95% CI 1.18-1.62; p<0.001).

Wearable vest may not fill the gap between the index acute Mi and the recommended time to reassess and consider ICD

Wearable Cardioverter-Defibrillator after Myocardial Infarction.

NEJM   2018; 379:1205-15

The optimal timing of implanting an ICD in patients with severe LV systolic dysfunction secondary to a MI is controversial with two previous studies showing no long-term mortality benefit from ICDs that had been implanted immediately after a MI. The VEST randomised trial examined the efficacy of a wearable ICD during the period before ICDs are currently recommended (40-90 days after MI) in patients who have had a MI and ejection fraction ≤35%. Eligible patients were randomised in a 2:1 ratio to either the Zoll LifeVest ICD and guideline directed medical therapy (n=1524) or guideline directed medical therapy alone (n=778). The primary endpoint was the composite of sudden death or death from ventricular tachyarrhythmia at 90 days. Secondary outcomes included death from any cause and nonarrhythmic death. The rates of arrhythmic death (1.6% vs. 2.4%; RR 0.67; 95% CI 0.37-1.21; p=0.18) and non-arrhythmic death (1.4% vs. 2.2%; RR 0.63; 95% CI 0-33-1.19; uncorrected p=0.15) were similar in the device/medical therapy and medical therapy alone groups. Death from any cause was lower in the ICD group (3.1% vs. 4.9%; RR 0.64; 95% CI 0.43-0.98; uncorrected p=0.04).

 

Attrition after vein graft pci not halted by DES versus BMS… ?surprising, or inevitable

Efficacy Over Time With Drug-Eluting Stents in Saphenous Vein Graft Lesions.

JACC  2018; 71:1973-82

The “Is Drug-Eluting-Stenting Associated with Improved Results in Coronary Artery Bypass Grafts” (ISAR-CABG) trial has indicated that DES were associated with superior clinical outcomes compared to BMS at 1-year follow-up. The current manuscript reports 5-year results of the study. ISAR-CABG randomised 610 patients with ≥50% de novo stenosis of a SVG to treatment with a DES (n=303) or a BMS (n=303). The primary endpoint was the combined incidence of death, MI, or TLR. Secondary endpoints were the composite of death or MI and TLR. At 5 years, the primary endpoint was similar between the DES and BMS groups (55.5% vs. 53.6%; p=0.89). Death or MI were also similar between the DES and BMS groups (32.8% vs. 36.6%; p=0.24), as were the rates for TLR (33.1% vs. 25.5%; p=0.27). 

Routine oxygen in PPCI patients has no benefit if they are normoxemic… other data show harm for O2 in these patients

Oxygen therapy in ST-elevation myocardial infarction

European Heart Journal, Volume 39, Issue 29, 1 August 2018, 2730–2739,

This study was conducted to determine whether supplemental oxygen in patients with STEMI impacts on procedure-related and clinical outcomes. The DETO2X-AMI trial randomized patients with suspected MI to receive oxygen at 6 L/min for 6–12 h or ambient air. In total, 2807 patients undergoing PPCI for STEMI were included (1361 received oxygen, vs. 1446 received ambient air). The prespecified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% vs. 7.5% (oxygen versus ambient air P = 0.27). There was no difference in the rate of death from any cause (P = 0.41), rate of rehospitalization for MI (P = 0.73), rehospitalization for cardiogenic shock (P = 0.95), or stent thrombosis (P = 0.64). Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis