choice of stent in svgs and ci aki meta analysis

1. Journal club
13-06-2017

2. March 2017

3. INTRODUCTION
• Coronary artery bypass graft surgery with ≥1 saphenous vein
grafts (SVGs) is a commonly selected mode of
revascularization for patients with multivessel coronary artery
disease.
• The long-term patency rates of SVGs, when compared with
arterial conduits, remain poor despite optimal secondary
prevention therapy.
• A sizeable proportion (10%–40%) of SVGs occlude within the
first year and with inexorable attrition at a rate of 2% to 5%
annually, which accelerates with graft age

4. • PCI of SVGs is often a preferred revascularization modality in
patients with significant SVG disease with 5% to 10% of all PCI
procedures being undertaken in SVGs.
• As old degenerative SVGs are usually of a large calibre and
these patients are frequently old and frail with multiple
comorbidities, BMS may be considered an appropriate choice.
• Different registries have shown that from one-third to half of
patients undergoing PCI of SVGs receive BMS.
• However, more recent data suggest a growing use of newer
generation DES in treating SVG disease.

5. • Only a few studies have compared BMS and DES for PCI of
SVGs and generally shown that use of DES in SVGs can reduce
the need for repeat revascularization but with no survival
benefit.
• However, these studies have largely compared either only
first-generation DES or a combination of first- and newer
generation DES against BMS with limited data on
contemporary DES platforms.

6. • Registry data from the Veterans Affairs CART Program suggest
the use of newer generation DES is associated with lower
mortality than BMS and similar rates of myocardial infarction
at long-term follow-up (>2 years), but there was no difference
in mortality or MI between first- and newer generation DES in
this study.
• In view of limited and divergent results in the
literature,investigators aimed to assess stent choice and
clinical outcomes after PCI to SVGs in patients receiving BMS,
first-generation DES, and newer generation DES in a large
unselected all-comer national data set from the BCIS (British
Cardiovascular Intervention Society).

7. METHODS

8. STUDY DESIGN AND DATA COLLECTION
• This was a retrospective analysis of prospectively collected
national data for all patients undergoing PCI of SVGs in the
United Kingdom from January 2006 to December 2013.

9. VARIABLES AND OUTCOMES COLLECTED
• Investigators collected data on participants’ demographics
(age, sex, smoking status, and family history of heart disease)
and comorbidities (diabetes mellitus, hypertension,
hyperlipidemia, previous MI, stroke, peripheral vascular
disease, and renal disease).
• In addition, data were also collected on left ventricular
ejection fraction, access site, use of glycoprotein IIb/IIIa
inhibitor, use of thrombectomy device, cardiogenic shock, use
of intra-aortic balloon pump, use of ventilatory support, and
use of distal protection devices.

10. • Patients undergoing PCI to an SVG were grouped into 3
cohorts based on stent type:
1. BMS group (including Titan-2)
2. First generation DES (Cypher, Taxus Liberte, Eucatax, Achieve,
Sorin, Costar stents)
3. Newer generation DES (Promus, Xience, Resolute, Biomatrix,
Endeavor, Biofreedom, Nobori, and Yukon stents).

11. • Investigators evaluated all-cause mortality at 30-day and 1-
year follow-up and major adverse cardiovascular events
(MACE; defined as a composite of in-hospital mortality, in-
hospital myocardial reinfarction, and target vessel
revascularization).

12. STATISTICAL METHODS
• Summary statistics are presented as mean±SD for continuous
data and percentage or proportions for categorical variables,
according to the stent group (BMS, first-generation DES, and
second-generation DES).
• The clinical characteristics of the 3 groups were compared
using ANOVA and χ2 tests for continuous and categorical
variables, respectively.
• The risk of adverse outcomes was estimated with multiple
logistic regressions.

13. RESULTS

14. STUDY COHORT
Flow diagram of participant inclusion

15. • A total of 5685 patients (38%)received BMS and 9318 (62%)
received DES.
• Among patients receiving DES, 2265 (24.3%) received first-
generation DES and 7053 (75.7%) received second-generation
DES.

16. • There was a temporal
change in the use of stents .
• In 2006,42% of patients
received BMS with the
remainder receiving first-
generation DES.
• By 2013, use of first-
generation DES had ceased
with the ratio of newer
generation DES:BMS being
78% to 22%, respectively.

17. CHARACTERISTICS OF PARTICIPANTS
CHARACTERISTICS OF PARTICIPANTS

18. CLINICAL OUTCOMES
• The highest unadjusted rates of in-hospital MACE and 30-day
and 1-year mortality were observed in the BMS group.
• We found that the in-hospital MACE rate according to stent
type was 3% (n=167), 1% (n=31), and 2% (103) forBMS, first-
generation DES, and second-generation DES,respectively

19. Adjusted MACE and mortality were
also significantly lower with the use of DES

20. DISCUSSION
• Study data derived from a large all-comer national registry of
patients undergoing PCI of SVG, suggest that use of DES is
associated with better outcomes when compared with BMS.
• There is reduction is MACE and mortality in DES-treated patients, in
particular those receiving newer generation DES.
• This study overcomes the limitations of small sample size seen in
the 3 randomized trial :
1. RRISC [Reduction of Restenosis in Saphenous Vein Grafts With
Cypher Sirolimus- Eluting Stent]
2. SOS [Stenting of Saphenous Vein Grafts]
3. ISAR-CABG [Efficacy Study of Drug-Eluting and Bare Metal Stents in
Bypass Graft Lesions]) comparing DES and BMS in SVG lesions.

21. • RRISC was a prospective, double-blind, randomized trial of
patients (n=75 patients; 96 SVG lesions) treated with first-
generation sirolimus-eluting Cypher DES (n=38 patients; 60
stents) or BMS (n=37 patients;54 stents).
• At 6-month follow up, the DES group had less in-stent
restenosis , target lesion revascularization , and target vessel
revascularization .

22. • The SOS trial randomized 80 patients with 112 lesions in 88
SVGs to a BMS (39 patients; 43 grafts; 55 lesions) or first-
generation paclitaxel-eluting Taxus DES (41 patients; 45
grafts; 57 lesions).
• Binary angiographic restenosis was substantially lower in the
DES group.
• During a median follow-up of 1.5 years, the DES group had
less target lesion revascularization and target vessel failure, a
trend toward less target vessel revascularization and MI.

23. • The larger ISAR-CABG trial (n=610) randomized patients with
diseased SVGs to DES (1 of the 3 types: permanent-polymer
paclitaxel-eluting stents, permanent-polymer sirolimus-
eluting stents, or biodegradable- polymer sirolimus-eluting
stents) and BMS .
• This trial reported a reduction in the primary end point of
MACE at 1 year in the DES group (DES 15.4% versus BMS
22.1%),which was mainly driven by a near 50% relative
reduction in the risk of target lesion revascularization (DES
7.2% versus BMS 13.1%), with no significant differences in
mortality.

24. • Study data provide supportive evidence that use of newer
generation DES is associated with improved outcomes and
survival in patients undergoing PCI in SVGs.
• DES use reduces restenosis, need for repeat revascularization
and associated adverse events.
• The newer generation DES with biocompatible and
bioresorbable polymers have low rate for stent thrombosis,
which is definitely lower than first-generation DES and
possibly also lower than BMS.
• DES use is generally associated with longer duration of dual
antiplatelet therapy, which may in turn be associated with a
reduction in adverse ischemic and thrombotic events

25. • There are no randomized data comparing newer versus first-
generation DES for the treatment of SVG disease.
• In a multicenter analysis of 172 real-world patients
comparing first-generation DES, SVG intervention with
sirolimus- and paclitaxel-eluting stents resulted in
nonsignificant differences in survival (HR, 1.28; 95% CI, 0.39–
4.25; P=0.69) and target vessel revascularization.
• Study data from a large all-comer national registry and
propensity matched cohort provides reassurance that the
newer generation DES seems effective and safe for the
treatment of SVG disease.

26. • Although BMS have conventionally been used in older,
multimorbid patients at higher risk of bleeding complications
where shorter DAPT duration would be preferable.
• In the recent LEADERS FREE trial using a polymer and carrier-
free biolimus coated BioFreedom stent was superior to a BMS
with respect to the primary safety and efficacy end points
when used with a 1-month course of DAPT in patients at high
risk of bleeding complications.
• It is therefore likely that the use of BMS in SVG will decline
further.

27. STUDY STRENGTHS AND LIMITATIONS
• Strengths of these data - they represent among the largest
analysis of PCI to SVG in contemporary practice, including an
almost complete collection of all PCI procedures performed in
England and Wales.
• They therefore reflect an all-comers, real-world experience
that includes many high risk patients who are often excluded
from randomized controlled trials.

28. LIMITATIONS
1. Although mortality tracking within the United Kingdom is
robust, the MACE outcomes were self-reported and were not
formally adjudicated. Therefore, the analysis was subject to
reporting biases, and complications may be under-reported.
2. Investigators did not have data for duration of DAPT.
3. Finally, study analysis was observational, with inherent
limitations of any such data analysis.

29. CONCLUSIONS
• In one of the largest analyses to date, it was observed that
patients receiving DES (particularly newer generation DES) for
the treatment of SVG disease have lower rates of in-hospital
MACE, 30-day mortality, and 1-year mortality, compared with
those receiving BMS.
• Patients undergoing PCI for SVG disease should therefore
receive a DES, unless any contraindication or higher risk of
bleeding with DAPT or requirement for a short DAPT course.

30. JACC February 2017

31. INTRODUCTION
• Contrast-induced acute kidney injury (CI-AKI), also known as
contrast-induced nephropathy, is a frequent complication
following angiographic procedures with significant impact on
health care costs and a powerful predictor of unfavourable
early and long-term outcomes.
• Following contrast administration, CI-AKI is defined as a rise in
serum creatinine (SCr) of 0.5 mg/dl (44.2 mmol/l) or a 25%
relative rise in SCr within 72 h of contrast exposure in the
absence of an alternative cause.

32. • Because accumulation of SCr is relatively slow, it requires 48
to 72 h to identify many cases of CI-AKI.
• Acute kidney injury up to 7 days post–contrast administration
could be considered CI-AKI.
• Patients usually have symptoms such as anuria, electrolyte
imbalance, hypotension, or hypertension and may need renal
replacement therapy (RRT).
• Incidence of CI-AKI - 1% to 2%.
• Incidence significantly higher in patients with diabetes
mellitus and pre-existing renal impairment.

33. • In patients with pre-existing renal impairment, the risk for CI-
AKI - as high as 50%.
• It is also procedure dependent, with 14.5% overall in patients
undergoing percutaneous coronary interventions compared
with 1.6% to 2.3% for diagnostic intervention.
• In patients undergoing percutaneous coronary intervention,
each 100 ml of contrast was associated with a 12% increased
risk for CI-AKI.

34. • The optimal treatment for preventing CI-AKI has not yet been
defined : trials of N-acetylcysteine, diuretic agents, dopamine,
calcium-channel blockers, atrial natriuretic peptides,
aminophylline, statins, and endothelin antagonists have
yielded contrasting results.
• Only periprocedural hydration is widely accepted to prevent
contrast nephropathy.

35. • Recently, a novel system aimed at reducing CI-AKI was
introduced.
• The RENALGUARD SYSTEM delivers intravenous fluids
matched to urine output with a combination of hydration with
normal saline at an initial dose bolus plus a low dose of
furosemide and continuous monitoring for a urine output
flow of >300 ml/h sustained for 6 h.
• The aim of this systematic review and metaanalysis was to
evaluate if furosemide with matched hydration using the
RenalGuard System effectively decreases the incidence of CI-
AKI in patients undergoing interventional procedures.

36. METHODS

37. SEARCH STRATEGY
• Investigators independently searched PubMed, Embase, and
the Cochrane Central Register of Clinical Trials (last updated
October 1, 2016) for appropriate reports.
• The search strategy aimed to include any randomized study
ever performed with furosemide with matched hydration with
the RenalGuard System compared with any control group in
adult humans in interventional cardiology settings

38. STUDY SELECTION
• References obtained from searches were first independently
examined at the abstract level by 2 investigators and then, if
potentially relevant, collected as complete reports.
• Eligible studies met the following PICOS criteria:
1. Population: adult hospitalized patients undergoing
interventional procedures;
2. Intervention: furosemide with matched hydration with the
RenalGuard System;
3. Comparison intervention: any type of control group;
4. Outcome: incidence of CI-AKI;
5. Study design: randomized controlled trials.

39. • The exclusion criteria were overlapping populations and
pediatric studies.
• Two investigators independently assessed selected studies for
the final analysis, with eventual divergences finally resolved
by consensus with a third investigator.

40. STUDY CHARACTERISTICS
• The primary outcome of the present review was the incidence
of CI-AKI.
• The secondary outcomes were need for RRT, mortality at
longest follow-up available, acute coronary syndromes, stroke
or transient ischemic attack, and adverse events.
• The outcomes were reported as per-study definition

41. DATA ANALYSIS
• To analyze the binary outcome, investigators calculated odds
ratio (OR) with 95% confidence interval (CI).
• Investigators also calculated the number needed to treat in
case of statistically significant results.
• To assess between-study heterogeneity, investigators used the
Cochran Q statistics.

42. RESULTS

43. CHARACTERISTICS OF INCLUDED STUDIES
Study Flow Diagram

44. • Four trials (698 patients) met the inclusion criteria and were
published between 2011 and 2016.
• All trials were performed in Italy.

46. CI-AKI

47. ANALYSIS TRIALS INCLUDED
(N)
RESULTS P FOR EFFECT I
2
PRIMARY ANALYSIS 4 Odds Ratio 0.31 [95% CI,
0.19, 0.50]
< 0.00001
4%
GFR < 60 ML/MIN AT
RANDOMIZATION
3 Odds Ratio 0.38 [95% CI,
0.22, 0.65]
0.0004
0%
CORONARY PROCEDURES 3
Odds Ratio 0.34 [95% CI,
0.21, 0.57]
< 0.0001
4%
ELECTIVE CORONARY
PROCEDURES
3
Odds Ratio 0.38 [95% CI,
0.22, 0.65]
0.0004
0%
URGENT CORONARY
PROCEDURES FOR NON–ST-
SEGMENT ELEVATION
ACUTE MYOCARDIAL
INFARCTION
1 Odds Ratio 0.11 [95% CI,
0.02, 0.57]
0.008 NA
TRANSCATHETER AORTIC
VALVE REPLACEMENT
1 Odds Ratio 0.17 [95% CI,
0.05, 0.63]
0.008 NA
`

48. OTHER CLINICAL OUTCOMES

49. SAFETY PROFILE AND ADVERSE EVENTS
Also ,the trials did not report any symptomatic electrolyte disorders.

50. DISCUSSION
• Furosemide with matched hydration by the RenalGuard
System may reduce the incidence of CI-AKI in high risk
patients undergoing interventional procedures,leading to a
significantly lower need for RRT.
• The effect is confirmed even when considering the subgroups
of patients with pre-existing renal impairment.

51. • Contrast media have direct toxic effect on renal tubular cells,
causing vacuolization and altered mitochondrial function.
• As a consequence, nitric oxide–mediated mechanism and a
prostaglandin induced vasodilatation are inhibited, leading to
vasoconstriction and consequently to ischemia of the vascular
supply of kidney medulla .

52. • The mechanism of action of the RenalGuard is not yet fully
elucidated, but one can postulate that the high urine output
(>300 ml/h) maintained during the procedure has a direct
protective effect on the tubular cells and improves
simultaneously renal medulla perfusion, thus
counterbalancing the direct and the ischemic effects induced
by the contrast media.

53. • It can be also speculated that the lower although not
significant rate of post-operative acute coronary syndromes
and stroke may reflect an additional protective effect in the
RenalGuard group at the cerebral and cardiac levels.
• Further data are needed to draw any conclusions.
• CI-AKI follows a benign course, and persistent renal
impairment and dialysis dependence are rare .
• The need for dialysis in <1% of patients with CI-AKI and in
about 3% of patients undergoing primary PCI for acute
coronary syndromes .
• In selected subgroups of patients, such as those with CKD or
diabetes mellitus, however, up to 7% require transient dialysis

54. • The lower rate of CI-AKI and especially the significant
reduction of RRT could also have a positive economic impact.
• Another crucial point is RenalGuard’s safety.
• According to randomized evidence, the RenalGuard showed a
similar risk profile compared with conservative treatment,
particularly for the systemic effect related to volume and
diuretic agent administration (pulmonary congestion and
electrolyte imbalance).

55. STUDY LIMITATIONS
• This meta-analysis included only 4 studies with high risk of
bias, and control regimens were not identical among trials.

56. CONCLUSION
• The main findings of this meta-analysis is that furosemide
with matched hydration by the RenalGuard System seems to
reduce the incidence of CI-AKI andRRT in high-risk patients
undergoing interventional procedures.
• Further independent high-quality multicenter randomized
trials should elucidate the effectiveness and safety of the
RenalGuard System in this population.