Medscape Conference Coverage, based on
selected sessions at the:
EuroPCR 2006 -- The Paris Course
on Revascularization
This activity is not
sanctioned by, nor a part of, EuroPCR 2006.
Cardiovascular Interventions in Women: Are All
Therapies Created Equal?
Luis Gruberg, MD, FACC
"There is certainly a void of knowledge as to how we
can optimize treatment for our female patients with CVD. More trials are an
absolute necessity to clarify the best therapeutic alternatives for this
important group of patients."
Introduction
More than 71 million Americans have 1 or more types of
cardiovascular disease (CVD).[1] CVD affects
men and women at similar rates (34% of each group), but the rate of mortality is
higher in women than in men (53% vs 47%).[1]
Similar disparities have been noted among victims of
myocardial infarction (MI). Each year, more than 1 million people suffer an MI;
50% of cases are fatal, and many of these deaths occur within 1 hour of symptom
onset. Data from the Framingham Heart Study show that more women than men will
die within 1 year of having an MI (38% vs 25%).[1]
In addition, in-hospital mortality after elective or emergency percutaneous
coronary intervention (PCI) is higher in women, while late mortality is similar
to that of male patients.[2]
The difference in outcomes between the sexes has been
attributed to a complex interplay of many factors, including the
underutilization of practice guideline-recommended therapies.[3]
For example, more than 1.2 million PCI procedures are performed annually in the
United States, but only an estimated 33% are performed in women. Data from the
2002-2003 Euro Heart Survey show that, in addition to being less likely to
undergo revascularization, women are also less likely to receive aspirin or
statins. These findings are troubling, given that women tend to have a higher
incidence of comorbid conditions at baseline, which also complicates outcomes.
Other attributable factors include that, compared with men, women: are more
likely to have a delayed onset of disease; usually present later and at an older
age; tend to be of smaller stature; and noninvasive testing is associated with a
lower predictive value.
Nevertheless, contemporary trials and registries have
shown that after adjustment for these factors, gender differences are virtually
eliminated, dismissing the idea that mortality risk is sex-specific.
Despite the fact that public service campaigns, such as
those initiated by the American Heart Association and the American College of
Cardiology, have increased the awareness of CVD risk in women among the general
population,[4] a recent survey of physicians
found that fewer than 1 in 5 physicians were aware that CVD was the leading
cause of death in women.[5]
Currently, there are only limited data on outcomes in
women following interventional procedures. While heavily underrepresented in
large clinical trials, subgroup analyses focusing on the outcomes of women
enrolled in these large studies will help to increase awareness in the medical
community, help facilitate care for our female patients, and rule out the
potential gender bias in revascularization techniques. A session regarding women
and percutaneous vascular interventions was held at the EuroPCR 2006 meeting.
Below are brief summaries from each of the presentations.
"Drug-Eluting Stents: Have They Improved
Outcomes?"
Presenter: Eberhard Grube, MD (Heart Center Siegburg,
Germany)
Drug-eluting stents (DES) have significantly reduced
restenosis after stent implantation in the coronary arteries. Target lesion
revascularization (TLR) rates have dropped from an average of 20% to as low as
6%. For this reason, 90% of all stents currently deployed in the United States
are DES, and similar trends are seen throughout the world.
Despite the widespread use of DES and its proven
effectiveness, previous studies have suggested that there are marked differences
in the diagnosis, treatment, and subsequent outcomes between men and women with
coronary heart disease. But subanalyses of the drug-eluting trials suggest
otherwise.
For example, the overall results of the SIRIUS trial[6]
found that use of the sirolimus-eluting stent was associated with a
significantly lower rate of TLR as compared with a bare-metal stent. A subgroup
analysis of the SIRIUS trial that compared outcomes by gender suggests that once
women are referred for cardiac catheterization, revascularization rates are
similar to those in men. Results of the analysis showed that the overall
findings of the main trial were not influenced by gender; use of the
sirolimus-eluting stent equally benefitted men and women in the trial (Figure
1).
Figure 1. SIRIUS: sirolimus-eluting
stent vs control -- target lesion revascularization rates by gender.
Similar results were observed in a subgroup analysis of
the TAXUS II study, in which the incidence rates of TLR and late loss were
significantly reduced in patients randomized to the paclitaxel-eluting stent (vs
control), regardless of gender (Figure 2). Although it is too early to make any
definitive conclusions, an analysis of the TAXUS IV trial suggests that use of
the paclitaxel-eluting stent in women was associated with lower rates of TLR and
target vessel revascularization (TVR) than those seen in men who received the
same treatment (Figure 3).
Figure 2. TAXUS II: paclitaxel-eluting
stent vs control -- target lesion revascularization (TLR) and late loss by
gender.
Figure 3. TAXUS IV: target lesion
revascularization (TLR) and target vessel revascularization (TVR) in
patients treated with the paclitaxel-eluting stent by gender.
So, do DES perform equally well in both male and female
patients? We can't say for sure from the data that are currently available, but
these subgroup analyses do suggest that the use of DES is associated with
favorable long-term results, regardless of gender differences.
"Acute Myocardial Infarction: Do Women Benefit
From Primary Angioplasty?"
Presenter: David Antoniucci, MD (Azienda
Ospedaliero-Universitaria Careggi, Florence, Italy)
Data from the National Registry of Myocardial Infarction
two (NRMI-2)[7] have shown that the rate of
in-hospital mortality is twice as high in younger women with MI as in their male
counterparts. This difference diminishes with age, however, and the risk then
becomes higher in older men.
In the first and second Primary Angioplasty in
Myocardial Infarction (PAMI-1 and PAMI-2) trials, there was no difference in
adjusted mortality between men and women. However, in the Stent-PAMI trial,
there was no beneficial effect of stents (vs plain balloon angioplasty) in women
(12% vs 15.5%, respectively;
P = .47). Furthermore, in this study, female gender was a strong
predictor of 1-year mortality (OR 2.24, CI 1.07-4.69, P = .032). Whereas
gender was not a predictor of 1-year mortality in the Controlled Abciximab and
Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial,
it was a predictor of major adverse cardiac events (HR 1.64, CI 1.24-2.17,
P = .0006).[8]
In an analysis of the Should We Emergently Revascularize
Occluded Coronaries for Cardiogenic Shock (SHOCK) registry,[9]
investigators initially found that in-hospital mortality was higher in women
than in men. However, after adjusting for differences in patient demographics
and treatment approaches, no significant difference was observed between the 2
groups.[10].
Overall, women tend to have a higher incidence of
comorbid conditions at baseline, which is associated with higher mortality rates
when compared with male counterparts. However, the benefit of early PCI in the
acute phase of MI is similar in women and men and, thus, any potential referral
bias for PCI based on gender should be avoided.
"Angioplasty or Surgery for Coronary Heart
Disease: What Is Best for a Woman?"
Presenter: Vassilios Voudris, MD (Onassis Cardiac
Surgery Center, Athens, Greece)
Once women are referred for catheterization,
revascularization rates and practices are similar to those seen in men. However,
women who undergo coronary artery bypass surgery (CABG) fare worse than men who
undergo the same procedure, with higher rates of in-hospital mortality and
cardiac readmissions. In part, these results may be attributed to the fact that
women are usually older, smaller in stature, receive less mammary grafts, have a
lower incidence of complete revascularization, and usually undergo the procedure
due to acute coronary syndromes (ACS).
Data from the second Arterial Revascularization
Therapies Study (ARTS II), analyzed according to gender, showed similar outcomes
between men and women with multivessel disease treated with a sirolimus-eluting
stent (Figure 4). In addition, in ARTS II, outcomes in female patients treated
with the DES were significantly better than those seen in female patients who
underwent CABG in the ARTS I trial.
Figure 4. ARTS II: outcomes of patients
treated with sirolimus-eluting stent by gender.
CVA = cerebrovascular
event; MACCE = major adverse cardiac and cerebrovascular event; MI =
myocardial infarction
These results demonstrate that PCI can be performed
safely and effectively in women, even in complex settings, and the procedure can
save lives and prevent future heart attacks, not just relieve symptoms.
Currently, women undergoing CABG have higher early mortality rates, but
excellent late outcomes following CABG surgery. Randomized trials are needed to
clarify the best revascularization procedure in women.
"Gender Differences in the Use of Adjunctive
Medical Therapies During Percutaneous Coronary Intervention"
Presenter: Alexandra J. Lansky, MD (Columbia Medical
Center, New York, NY)
Women are more likely to have aspirin resistance and
also face an increased risk of bleeding and vascular complications after PCI in
any setting. Although no sex-specific data exist for the use of thienopyridines,
recommendations are similar for men and women.
In women with ACS, studies such as the Treat Angina with
Aggrastat and Determine Cost of Therapy With an Invasive or Conservative
Strategy (TACTICS-TIMI 18)[11] showed that
treatment with an early aggressive approach yielded better outcomes than
conservative treatment (although the benefit was not as significant as in male
patients). By contrast, among women, the Fragmin and Fast Revascularization
During Instability in Coronary Artery Disease (FRISC II)[12]
study found that an aggressive approach (vs conservative treatment) was
associated with worse outcomes, and the results of the Randomized Intervention
Trial of Unstable Angina (RITA 3)[13]
failed to show a difference between the 2 approaches in women. Among male
patients, however, all 3 studies showed a benefit from an early invasive
approach.
Regarding the use of antiplatelet agents in patients
undergoing PCI, a meta-analysis[14] of more
than 6500 patients (27% female; 73% male) from 3 trials showed that the benefit
of the glycoprotein IIb/IIIa inhibitor (GPI) abciximab in preventing death, MI,
or TVR was independent of gender. However, female patients had a significantly
higher rate of bleeding complications with abciximab.
An analysis of the CADILLAC trial[8]
found that women with acute MI who underwent primary stenting with or without
the addition of abciximab had significantly lower rates of MACE and TVR at 12
months compared with women treated with angioplasty with or without abciximab
treatment. The addition of abciximab to primary stenting also significantly
reduced the rate of TVR at 30 days compared with stenting alone (P = .03)
and was not associated with any significant increases in the bleeding
complications. But the early benefit was no longer significant at 1 year. There
was no significant survival benefit of one treatment strategy over another.
Similar findings were noted among women in the
Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events II
(REPLACE-2) trial, which randomized patients undergoing elective or urgent PCI
to use of the direct thrombin inhibitor, bivalirudin, plus provisional GPI use
or heparin plus planned GPI use. In women, the use of bivalirudin plus
provisional GPI use was not inferior to the use of heparin plus provisional GPI
therapy, and there were no differences in incidence of the primary endpoint
(composite of death, MI, urgent revascularization, and major in-hospital
bleeding complications at 30 days) or in the rate of death at 30 days; the
results remained unchanged at 6 months. However, use of bivalirudin plus
provisional GPI was associated with significant reductions in the rate of minor
and major bleeding complications vs bleeding rates in women treated with heparin
plus GPI (Figure 5).
Figure 5. REPLACE-2: bleeding
complications in women.
Among women, independent predictors of bleeding were the
use of heparin plus GPI. In addition, women had a higher incidence of minor and
major TIMI bleeding compared with men, and female gender was found to be an
independent predictor of major bleeding complications in patients undergoing PCI
(OR 1.61, CI 1.14-2.29,
P = .008).
Excess dosing of GPI inhibitors may be responsible for a
higher rate of bleeding complications in women. In an observational analysis of
the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress
Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines?)[15]
registry, patients who received an excess dose of GPI had a significantly
increased risk of major bleeding. Female gender was an independent predictor of
receiving an excess dose. These findings emphasize the need to give careful
attention to ensure proper GPI dosing in women in order to minimize bleeding
complications.
In conclusion, the results of these subgroup analyses
demonstrate that in female patients, the use of anticoagulants during PCI yields
similar clinical outcomes to those observed in men. However, female patients are
at higher risk of bleeding complications at standard male dosage. Therefore,
alterations in the use of these drugs are needed, such that the use of GPI is
recommended in women with high-risk ACS but should be avoided in low-risk women.
In addition, clinicians may want to consider using a lower dose in women treated
with heparin plus GPI. Furthermore, bleeding complications could be reduced 2-
to 3-fold in women by using weight-adjusted heparin dosing and earlier sheath
removal.
"Is There Any Indication for Carotid Artery
Stenting in Women?"
Presenter: Bernhard Reimers, MD (Miro General
Hospital, Mirano, Italy)
Stroke is a devastating disease, both for the patient
and his or her family. Stroke presentation in women is usually worse than in
men. Female patients are usually older, have more in-hospital complications and
a longer length of hospitalization stay.[16]
Furthermore, previous studies have shown significant anatomical differences in
the distribution of atherosclerotic disease between men and women. Whereas men
have a larger atherosclerotic plaque area that is usually distributed distal to
the carotid bulb in the internal carotid artery, in women, the stenosis is
usually more severe and is usually found in the external carotid artery.[17]
However, there is no difference in the length of stenosis.
Outcomes following stroke treatment also vary between
men and women. For example, women tend to respond better to medical therapy than
men do,[18] and while they may have similar
outcomes following carotid endarterectomy, women tend to have higher rates of
restenosis (17.2% vs 6.3%).[19]
In the North American Symptomatic Carotid Endarterectomy
Trial (NASCET),[20] the risk of stroke at 5
years in female patients with a degree of stenosis of 50% to 69% was similar for
patients receiving medical treatment and those undergoing carotid
endarterectomy, whereas in male patients, carotid endarterectomy was associated
with a significant reduction in the risk of stroke relative to medical therapy.
Similar results were observed in the Asymptomatic Carotid Surgery Trial (ACST),[21]
where the benefits associated with deferred endarterectomy were less pronounced
in women than in men. Carotid artery stenting, a less invasive approach than
surgical endarterectomy, is also an effective treatment in both men and women.
In the Italian/German Carotid Artery Stenting Registry, for example, major
stroke, minor stroke, and death rates were similar in men and women (Figure 6).
Figure 6. Italian/German CAS Registry:
stroke/death at 30 days.
In summary, despite gender differences in the anatomy of
carotid arteries and worse outcomes following stroke in women, the procedural
results of carotid endarterectomy and carotid artery stenting are similar
between men and women. Unfortunately, men are more likely to undergo
endarterectomy and stenting than women are. To reduce the risk of stroke, more
women should be referred for invasive treatment. Finally, indications for
endarterectomy and carotid artery stenting should be equal for men and women.
Viewpoint
As physicians, we need to remind ourselves that CVD
accounts for the vast majority of death in female patients, and affects a higher
proportion of female than of male patients. Despite this important statistic,
women have been consistently underrepresented in major trials, and the benefits
of interventional therapies have yet to be studied solely in women. Instead, the
overall findings from trials are applied universally to both men and women.
However, as illustrated by the aforementioned analyses,
which are limited by their small sample size, disease presentation and outcomes
tend to vary between the sexes. In part, this is attributable to the fact that
women usually present later following symptom onset and are older at the time of
presentation, and have more risk factors, a smaller body surface area, worse
short-term outcomes, and higher rates of periprocedural complications,
especially bleeding.
There is certainly a void of knowledge as to how we can
optimize treatment for our female patients with CVD. More trials are an absolute
necessity to clarify the best therapeutic alternatives for this important group
of patients.
References
- Thom T, Haase N, Rosamond W, et al; American Heart
Association Statistics Committee and Stroke Statistics Subcommittee. Heart
disease and stroke statistics -- 2006 update: a report from the American
Heart Association Statistics Committee and Stroke Statistics Subcommittee.
Circulation. 2006;113:e85-151. Abstract
- Lansky AJ, Hochman JS, Ward PA, et al. Percutaneous
coronary intervention and adjunctive pharmacotherapy in women: a statement
for healthcare professionals from the American Heart Association.
Circulation. 2005;111:940-953. Abstract
- Wenger NK. Coronary heart disease in women:
highlights of the past 2 years -- stepping stones, milestones and
obstructing boulders. Nat Clin Pract Cardiovasc Med. 2006;3:194-202.
Available at: http://www.medscape.com/viewarticle/529700.
- Mosca L, Mochari H, Christian A, et al. National
study of women's awareness, preventive action, and barriers to
cardiovascular health. Circulation. 2006;113:525-534. Abstract
- Mosca L, Linfante AH, Benjamin EJ, et al. National
study of physician awareness and adherence to cardiovascular disease
prevention guidelines. Circulation. 2005;111:499-510. Abstract
- Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting
stents versus standard stents in patients with stenosis in a native coronary
artery. N Engl J Med. 2003;349:1315-1323. Abstract
- Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz
HM. Sex-based differences in early mortality after myocardial infarction.
National Registry of Myocardial Infarction 2 Participants. N Engl J Med.
1999;341:217-225. Abstract
- Lansky AJ, Pietras C, Costa RA, et al. Gender
differences in outcomes after primary angioplasty versus primary stenting
with and without abciximab for acute myocardial infarction: results of the
Controlled Abciximab and Device Investigation to Lower Late Angioplasty
Complications (CADILLAC) trial. Circulation. 2005;111:1611-1618. Abstract
- Hochman JS, Tamis JE, Thompson TD, et al. Sex,
clinical presentation, and outcome in patients with acute coronary
syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in
Acute Coronary Syndromes IIb Investigators. N Engl J Med. 1999;341:226-232.
Abstract
- Wong SC, Sleeper LA, Monrad ES, et al; SHOCK
Investigators. Absence of gender differences in clinical outcomes in
patients with cardiogenic shock complicating acute myocardial infarction. A
report from the SHOCK Trial Registry. J Am Coll Cardiol. 2001;38:1395-1401.
Abstract
- Glaser R, Herrmann HC, Murphy SA, et al. Benefit of
an early invasive management strategy in women with acute coronary
syndromes. JAMA. 2002;288:3124-3129. Abstract
- Lagerqvist B, Safstrom K, Stahle E, Wallentin L,
Swahn E. Is early invasive treatment of unstable coronary artery disease
equally effective for both women and men? FRISC II Study Group
Investigators. J Am Coll Cardiol. 2001;38:41-48. Abstract
- Clayton TC, Pocock SJ, Henderson RA. Do men benefit
more than women from an interventional strategy in patients with unstable
angina or non-ST-elevation myocardial infarction? The impact of gender in
the RITA 3 trial. Eur Heart J. 2004;25:1641-1650. Abstract
- Cho L, Topol EJ, Balog C, et al. Clinical benefit of
glycoprotein IIb/IIIa blockade with Abciximab is independent of gender:
pooled analysis from EPIC, EPILOG and EPISTENT trials. Evaluation of 7E3 for
the Prevention of Ischemic Complications. Evaluation in Percutaneous
Transluminal Coronary Angioplasty to Improve Long-Term Outcome with
Abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor
for Stent. J Am Coll Cardiol. 2000;36:381-386. Abstract
- Alexander KP, Chen AY, Roe MT, et al. Excess dosing
of antiplatelet and antithrombin agents in the treatment of non-ST-segment
elevation acute coronary syndromes. JAMA. 2005;294:3108-3116. Abstract
- Roquer J, Campello AR, Gomis M. Sex differences in
first-ever acute stroke. Stroke. 2003;34:1581-1585. Abstract
- Schulz U, Rothwell P. Sex differences in carotid
bifurcation anatomy and the distribution of atherosclerotic plaque. Stroke.
2001;32:1525-1531. Abstract
- Dick P, Sherif C, Sabeti S, Amighi J, Minar E,
Schillinger M. Gender differences in outcome of conservatively treated
patients with asymptomatic high grade carotid stenosis. Stroke.
2005;36:1178-1183. Abstract
- Chang J, Stein T. Ten-year outcome after saphenous
vein patch angioplasty in males and females after carotid endarterectomy.
Vasc Endovascular Surg. 2002;36:21-27. Abstract
- Alamowitch S, Eliasziw M, Barnett HJ; North American
Symptomatic Carotid Endarterectomy Trial (NASCET); ASA Trial Group; Carotid
Endarterectomy (ACE) Trial Group. The risk and benefit of endarterectomy in
women with symptomatic internal carotid artery disease. Stroke.
2005;36:27-31. Abstract
- Halliday A, Mansfield A, Marro J. Prevention of
disabling and fatal strokes by successful carotid endarterectomy in patients
without recent neurological symptoms: randomised controlled trial. Lancet.
2004;363:149
TAXUS ATLAS: Evaluation of the TAXUS Libert?vs
TAXUS Express -- 9-Month Clinical Events
Luis Gruberg, MD, FACC
"This study will help pave the road for the next
generation of drug-eluting stents. The goal of the present study was to show
that there are no performance differences between these 2 stents, and that goal
was achieved."
Presenter: Mark A. Turco, MD (Washington Adventist
Hospital, Takoma Park, Maryland), on behalf of the TAXUS ATLAS Investigators
The market-approved TAXUS Express
paclitaxel-eluting polymer-coated stent (Boston Scientific Corporation, Natick,
Massachusetts) has been shown to be effective for the treatment of simple to
complex lesions, including de novo lesions, long lesions, lesions in
small vessels, and, most recently, in-stent restenosis as studied in the series
of TAXUS trials.
The TAXUS Libert?/I>
represents the "next generation" drug-eluting stent system. The device has
thinner struts and continuous cell architecture; provides greater flexibility
and lower profile; and offers better side-branch access.
The TAXUS ATLAS trial was designed to demonstrate that
the TAXUS Libert?/I> is noninferior in efficacy to the TAXUS Express control
stent system.
Study Design
The TAXUS ATLAS is a multicenter, single-arm study that
enrolled 871 patients at 61 global sites.
Inclusion Criteria
- De novo lesions, 10-28 mm in length
- Reference vessel diameter 2.5-4.0 mm
- Treated with a single stent
Primary Endpoint: Noninferiority of 9-month
target vessel revascularization (TVR)
The trial compared outcomes of patients treated with the
TAXUS Libert?/I> stent (n = 871) with those of a case-matched control group of
patients from the TAXUS IV and V trials treated with the TAXUS Express stent (n
= 991).
Results
Quantitative and qualitative angiographic
characteristics showed that patients treated with the TAXUS Libert?/I> had
longer lesions and more tortuosity, calcification, branch vessel disease, and
B2/C type lesions than did control patients (Table). The groups were well
matched for other baseline characteristics.
Table. TAXUS ATLAS: Angiographic Characteristics
| Parameter |
Control
(n = 991) |
TAXUS Libert?/I>
(n = 871) |
| RVD (mm) |
2.79 ? 0.49 |
2.75 ? 0.50 |
| MLD (mm) |
0.92 ? 0.34* |
0.85 ? 0.36 |
| % DS |
66.8 ? 10.8 |
69.1 ? 11.8* |
| Lesion length (mm) |
13.60 ? 6.11 |
14.76 ? 6.61* |
| Angulation (degree) |
25.9 ? 18.4 |
33.8 ? 17.8* |
| Tortuosity (%) |
8.4 |
13.1? |
| Calcification (%) |
23.1 |
29.8? |
| Branch vessel disease (%) |
5.0 |
10.9* |
| B2/C lesions (%) |
61.2 |
75.5* |
*P < .001; ?P = .0011;
?P = .0012
DS = direct stenting; MLD = minimum
lumen diameter; RVD = reference vessel diameter
Use of the TAXUS Libert?/I> device was associated with
improved procedural performance. Procedural time, number of post-dilations,
ratio of stent length to lesion length, as well as the need for bailout
glycoprotein IIb/IIIa inhibitor use were all significantly lower in the TAXUS
Libert?/I>-treated group.
At 9-month follow-up, the primary noninferiority
endpoint was met -- by intention-to-treat analysis, there was no difference in
the rate of TVR between the control and TAXUS Libert?/I> groups (7.1% vs 8.0%,
respectively; P = .48). The individual endpoints of the study were also similar
(Figure). In addition, the rates of stent thrombosis were low and did not differ
between the 2 groups (0.7% and 0.8%).
Figure. TAXUS ATLAS: events at 9-month
follow-up.
MACE = major adverse cardiac events; MI = myocardial
infarction; TLR = target lesion revascularization; TVR = target vessel
revascularization
Conclusions
- The primary endpoint of the study was met -- the
TAXUS Libert?/I> is as safe and effective as the TAXUS Express stent system.
- Despite the presence of more complex lesions in the
TAXUS Libert?/I>-treated group, this stent demonstrated improved performance
and comparable clinical and angiographic outcomes to those of the TAXUS
Express-treated group.
Viewpoint
This study will help pave the road for the next
generation of drug-eluting stents. The goal of the present study was to show
that there are no performance differences between these 2 stents, and that goal
was achieved.
As noted by investigators, the TAXUS ATLAS program will
continue to evaluate use of the TAXUS Libert?/I> stent in direct stenting and
for the treatment of small vessels and long lesions.
The research in this article was supported by Boston
Scientific Corporation.
TAXUS VI: TAXUS MR Stent in Complex Lesions --
3-Year Clinical Results
Luis Gruberg, MD, FACC
"Representing real-world practice, the TAXUS VI trial
shows us that the TAXUS MR stent is extremely effective in treating high-risk
patients with very complex lesions, and the results are sustained over the long
term."
Presenter: Keith D. Dawkins, MD (Southampton
University Hospital, Southampton, United Kingdom), on behalf of the TAXUS VI
Investigators
TAXUS VI was a double-blind, randomized, superiority
trial that compared the TAXUS MR (moderate release; Boston Scientific, Natick,
Massachusetts) paclitaxel-eluting stent with bare-metal stent controls in
complex lesions. The TAXUS MR stent, which is not commercially available,
provides 3 times more local drug release than the market-approved TAXUS SR (slow
release) stent.
In TAXUS VI, a total of 446 patients were randomized to
TAXUS MR or control. The 1- and 2-year follow-up results have been previously
reported. At the EuroPCR 2006 meeting, 3-year clinical follow-up, available in
98.1% of patients (n = 210 in each study arm), was presented.
The overall patient cohort enrolled in TAXUS VI
represented the most complex, high-risk population of any drug-eluting stent
trial, characterized by long lesions, small vessels, and a high incidence of
diabetes (Table). Baseline characteristics did not differ between the 2 groups.
Table. TAXUS VI: High-Risk Characteristics of Overall
Patient Cohort
| Characteristic |
Patients
(N = 446) |
| Lesion length (mm) |
20.6 |
| Total stent length (mm) |
33.4 |
| AHA/ACC type C lesions (%) |
55.6 |
| Small vessels (< 2.5 mm) (%) |
27.8 |
| Overlapping stents (%) |
27.8 |
| PCI in an additional nontarget vessel
(%) |
23.5 |
| Diabetes (%) |
20.0 |
| Insulin-dependent (%) |
39.3 |
AHA/ACC = American Heart Association/American
College of Cardiology; PCI = percutaneous coronary intervention.
Results
As noted at 1-year and 2-year follow-up, freedom from
target lesion revascularization (TLR) at 3 years remained significantly better
in patients randomized to the TAXUS MR stent (Figure 1). The overall number
needed to treat to prevent 1 TLR was 10.75 patients.
Figure 1. TAXUS VI: target lesion
revascularization (TLR) at 1-, 2-, and 3-year follow-up.
Other clinical endpoints at 3 years were similar between
the 2 arms (Figure 2). In the TAXUS MR arm, there was 1 case of subacute stent
thrombosis and 1 case of late thrombosis, and in the control arm, there were 2
cases of subacute stent thrombosis.
Figure 2. TAXUS VI: clinical events at
3-year follow-up.
MACE = major adverse cardiac events; NQMI = non-Q-wave
myocardial infarction; TLR = target lesion revascularization; TVR = target
vessel revascularization.
Conclusions
- TAXUS VI remains the trial to recruit patients with
the most complex lesions.
- Follow-up rates are exceedingly high, which
strengthens the reliability of the data.
- These results confirm the long-term clinical safety
and efficacy of the TAXUS MR stent.
Viewpoint
As shown in the entire series of TAXUS studies, the use
of a paclitaxel-eluting stent has yielded consistent results demonstrating its
effectiveness at reducing the rates of TLR. Whereas earlier trials evaluated
less complex lesions, the TAXUS VI trial shows us that the stent is also
extremely effective in treating high-risk patients with very complex lesions.
Such evidence provides support for the use of this stent in real-world practice,
and the long-term data presented at this meeting attest to the safety of the
TAXUS MR stent.
The research in this article was supported by Boston
Scientific Corporation.
SESAMI: Sirolimus Stent vs Bare Stent in Acute
Myocardial Infarction
Luis Gruberg, MD, FACC
". . . the SESAMI results are encouraging and provide
further proof of the safety of sirolimus-eluting stents in STEMI patients. Such
findings are likely to add to the growing list of available indications for
drug-eluting stents."
Presenter: Maurizio Menichelli, MD (San Camillo
Hospital, Rome, Italy)
Background
Primary percutaneous coronary intervention (PCI) in the
acute phase of myocardial infarction (MI) is the treatment of choice in patients
presenting in the early hours of an ST-segment MI (STEMI). Lesions in these
patients are considered to be at especially high risk for restenosis. Until now,
bare-metal stents have been the treatment of choice for these lesions.
The Sirolimus Stent vs Bare Stent in Acute Myocardial
Infarction (SESAMI) trial was designed to assess the impact of the
sirolimus-eluting stent on restenosis rates in STEMI patients undergoing primary
PCI.
Study Design
SESAMI was an open label, 1:1 study that randomized
patients to either sirolimus-eluting or bare-metal stent placement. Patients
with left main lesions, graft lesions, or those who were in shock were excluded
from the trial.
Primary Endpoint: Angiographic restenosis at 1
year
Secondary Endpoints
1-year rates of:
- Target lesion revascularization (TLR)
- Target vessel revascularization (TVR)
- Major adverse cardiac events (MACE)
- Target vessel failure (TVF)
Results
A total of 423 patients with acute MI were treated
during the study period, of which 320 were evenly randomized to a study arm (n =
160 for each arm); 103 patients were excluded from the trial. Baseline clinical
and procedural characteristics of randomized patients are shown in the Table.
Table. SESAMI: Baseline Clinical and Procedural
Characteristics
| |
Sirolimus
(n = 160) |
Control
(n = 160) |
P |
| Clinical Characteristics |
| Age (yrs) |
62 |
61 |
.35 |
| Female (%) |
18 |
19 |
.36 |
| Diabetes (%) |
18 |
24 |
.13 |
| Hypertension (%) |
53 |
59 |
.2 |
| Smokers (%) |
57 |
49 |
.1 |
| S/P MI (%) |
6 |
13 |
.04 |
| S/P PCI (%) |
9 |
10 |
.38 |
| Killip class ≥ 2 (%) |
8 |
9 |
.38 |
| Rescue PCI (%) |
18 |
18 |
.53 |
| Infarct-related artery LAD (%) |
47 |
53 |
.29 |
| Procedural Outcomes |
| Acute success (%) |
98.2 |
98.8 |
.47 |
| TIMI 3 Preprocedural (%) |
17 |
19 |
.58 |
| TIMI 3 Postprocedural (%) |
93.8 |
96.2 |
.35 |
| Stent length (mm) |
20.8 |
18.2 |
.02 |
| Stent size (mm) |
3.02 |
3.14 |
.01 |
LAD = left anterior descending artery; MI =
myocardial infarction; PCI = percutaneous coronary intervention; S/P =
status-post; TIMI = Thrombolysis in Myocardial Infarction
In-hospital outcomes were similar between the 2 groups
(Figure 1). At 1-year angiographic follow-up, restenosis rates were
significantly higher in patients treated with bare-metal stents (Figure 2).
Overall, the use of a sirolimus-eluting stent was associated with a 56%
reduction in binary restenosis and a 64% reduction in clinically driven
restenosis relative to control.
Figure 1. SESAMI: In-hospital outcomes.
MI = myocardial infarction; SES = sirolimus-eluting stent
Figure 2. SESAMI: Angiographic 1-year
follow-up.
RR = risk reduction; SES = sirolimus-eluting stent
Similarly, all other endpoints (TLR, TVR, MACE, and TVF)
were significantly lower in patients treated with the sirolimus-eluting stent
(Figure 3). Acute and subacute stent thrombosis rates were low in both the
sirolimus and control groups (acute, 0.6% vs 0.6%; subacute, 3.1% vs 3.7%). Of
interest, by multivariate logistic regression analysis, female sex and
bare-metal stents were predictors of binary restenosis at 1 year (OR 5.3 and
3.8, respectively).
Figure 3. SESAMI: Clinical outcomes at
1-year follow-up.
MACE = major adverse cardiac events; RR = risk
reduction; SES = sirolimus-eluting stent; TLR = target lesion
revascularization; TVF = target vessel failure; TVR = target vessel
revascularization
Conclusion
The use of sirolimus-eluting stents in acute STEMI
patients undergoing primary PCI is safe and is associated with significantly
lower rates of restenosis when compared with bare-metal stents.
Viewpoint
Although SESAMI is a small, single-center study
involving a limited number of patients, its results confirm those from larger
trials recently presented at the American College of Cardiology meeting.
Unfortunately, due to time constraints of the late-breaking trial session at the
EuroPCR meeting, only succinct data were presented, leaving crucial information
regarding the way these trials were performed outstanding. This significantly
limits our ability to interpret these results on a general scale.
Nevertheless, the SESAMI results are encouraging and
provide further proof of the safety of sirolimus-eluting stents in STEMI
patients. Such findings are likely to add to the growing list of available
indications for drug-eluting stents.
SPIRIT First: Durable Polymer
Everolimus-Eluting Stent vs Bare-Metal Coronary Stent -- 2-Year Follow-up
Luis Gruberg, MD, FACC
"The results of this feasibility trial provided the
basis for additional phase 3 studies involving a larger number of patients, the
results of which we eagerly anticipate."
Presenter: Jan J. Piek, MD, University of Amsterdam
(Amsterdam, The Netherlands)
SPIRIT FIRST was a prospective, randomized,
single-blind, feasibility trial that compared the safety and effectiveness of
XIENCE V everolimus-eluting coronary stent (3.0 x 18 mm) vs the ML Vision stent
(Boston Scientific Corporation, Natick, Massachusetts [formerly Guidant
Corporation]). Enrollment of the 60-patient study began in April 2004, and the
2-year follow-up results were presented at the EuroPCR 2006 meeting.
Inclusion Criteria
- Stable angina
- Single de novo coronary lesion
- Target vessel reference diameter ≥ 2.8 mm and ≤ 3.2
mm
- Target lesion stenosis ≥ 50%
- Target lesion length ≤ 12 mm
Exclusion Criteria
- Within 3 days of acute myocardial infarction (MI)
- Left ventricular ejection fraction ≤ 30%
- Taking chronic anticoagulation therapy
- Prior (< 1 year) drug-eluting stent implantation
- Lesion located within 2 mm of the origin of the left
anterior descending artery or left circumflex or within 2 mm of a
bifurcation
Primary Endpoint: Angiographic in-stent late loss
Secondary Endpoints
- In-stent and in-segment binary restenosis
- In-stent and in-segment percent diameter stenosis
- In-stent percent volume obstruction
Results
Angiographic in-stent late loss (primary endpoint) was
0.10 ? 0.23 mm in the group receiving the everolimus-eluting stent vs 0.84 ?
0.36 in the control arm. The major secondary endpoint, in-stent percent volume
obstruction, was also lower in the everolimus-eluting stent arm than in the
control arm (8.6 ? 10.7% vs 29.0 ? 13.9%, respectively).
Two-year clinical outcomes were favorable, with a
clinically driven target lesion revascularization rate of 7.7% in the
everolimus-eluting stent arm vs 21.4% in the control arm. Major adverse cardiac
events (MACE) were also significantly lower in the treatment group (3.8% vs
25%). There were no cases of acute, subacute, or late stent thrombosis in either
the everolimus or the control arms of the study through 2 years (patients were
treated with 3 months of clopidogrel following device implantation).
Conclusions
- The 2-year clinical follow-up results demonstrate
continued safety of the XIENCE V everolimus-eluting stent, without the
occurrence of additional MACE and a 3.8% device-related MACE.
- There were no reports of early or late stent
thrombosis.
Viewpoint
Despite the limited number of patients, the results from
SPIRIT FIRST are favorable. The investigators were very cautious and did not
take big risks with this new stent, as reflected in the patient population
studied. The results of this feasibility trial provided the basis for additional
phase 3 studies involving a larger number of patients, the results of which we
eagerly anticipate. The lack of late stent thrombosis with a rather short course
of clopidogrel is encouraging, but larger studies are needed to draw definitive
conclusions about the optimal length of time for clopidogrel to be administered
after stenting.
The research in this article was supported by Boston
Scientific Corporation.
DEAR-MI: Dethrombosis to Enhance Acute
Reperfusion in Myocardial Infarction
Luis Gruberg, MD, FACC
"Although the simple aspiration device showed a
beneficial effect, I must say that I am somewhat skeptical of these results. .
."
Presenter: Paola Colombo, MD (Niguarda Hospital,
Milan, Italy)
Background
The use of a thrombus extraction device may limit
thrombus burden and/or distal embolization during percutaneous coronary
intervention (PCI) in acute myocardial infarction (AMI) patients. Previous
trials have failed to show a beneficial effect of extraction devices in these
patients.
The Pronto (Vascular Solutions, Inc., Minneapolis,
Minnesota) extraction catheter is described as a "simple, friendly,
single-operator" rapid exchange system that allows for thrombus aspiration with
a syringe while crossing the thrombus inside the infarct-related artery.
The Dethrombosis to Enhance Acute Reperfusion in
Myocardial Infarction (DEAR-MI) trial was designed to assess the impact of the
Pronto aspiration device on acute reperfusion in AMI patients.
Study Design
DEAR-MI was a 1:1 open-label study that randomized AMI
patients within 12 hours of symptom onset to either thrombus aspiration or
standard PCI. All patients underwent stenting and were concomitantly treated
with abciximab.
Primary Endpoint: ST-segment resolution
Secondary Endpoints: Angiographic analysis of
myocardial blush score, TIMI blood flow, TIMI frame count, and no reflow
Results
A total of 148 patients with AMI were treated during the
study period and evenly randomized to thrombus aspiration (n = 74) or to
standard PCI (n = 74). Baseline characteristics of patients enrolled in the
study are shown in the Table.
Table. DEAR-MI: Baseline Characteristics
| |
Pronto
(n = 74) |
Control
(n = 74) |
| Age (yrs) |
57 |
59 |
| Female (%) |
16 |
24 |
| Diabetes (%) |
21 |
15 |
| Hypertension (%) |
37 |
46 |
| Smokers (%) |
54 |
60 |
| Chronic renal failure (%) |
1 |
1 |
| Anterior wall infarction (%) |
42 |
51 |
| Killip class > 1 (%) |
4 |
5 |
| Ejection fraction (%) |
53 |
51 |
Procedural success was 100% in the Pronto arm and 99% in
the control group. Use of the device increased the procedural time by only 3
minutes, and debris was visible in 93% of patients. Initial TIMI 0-1 flow was
seen in 80% and 76% of Pronto and control patients, respectively. The use of the
extraction device permitted direct stenting in 70% of patients compared with 24%
of patients in the control arm (P < .0001). Final TIMI 3 flow was achieved in
89% of patients treated with the device and in 78% of patients in the control
arm (Figure 1).
Figure 1. DEAR-MI: final coronary
epicardial flow.
ST-segment resolution was significantly better in
patients treated with the Pronto device (Figure 2). Myocardial blush grade was
also significantly better in patients treated with the device, as reflected by
lower peak creatine kinase (CK)-MB levels.
Figure 2. DEAR-MI: ST-segment
resolution.
Patients treated with the device also had a
significantly lower rate of cath lab complications (Figure 3). Clinical events
at 6-month follow-up were very low and did not differ between the device and
control groups (1 event vs 3 events, respectively).
Figure 3. DEAR-MI: cath-lab
complications.
Conclusions
- Thrombus removal with the Pronto catheter in AMI
patients undergoing primary PCI is safe and easy to perform.
- Use of the device is associated with improved
myocardial reperfusion.
- The device may change PCI technique by increasing the
use of direct stenting.
Viewpoint
DEAR-MI is a small, single-center study that included a
limited number of patients. Although the simple aspiration device showed a
beneficial effect, I must say that I am somewhat skeptical of these results as I
have used the device myself.
In order to really assess the benefit (or lack thereof),
the trial should have been designed to compare the device with a sham procedure,
which would mean passing the catheter without doing aspiration. This approach
would have allowed us to assess the beneficial effect of the aspiration and not
of the Dotter effect (angiographic changes). Ongoing trials will help further
clarify these results.
PREMIAR: Protection of Distal Embolization in
Acute Myocardial Infarction
Luis Gruberg, MD, FACC
"The reasons for these findings likely represent our
lack of a complete understanding of the factors involved in no-reflow/distal
embolization phenomena."
Presenter: Jorge Belardi, MD (Institute
Cardiovascular de Buenos Aires, Argentina), on behalf of the PREMIAR
Investigators
Background
The use of a distal embolic protection device may limit
the rate of distal embolization during percutaneous coronary intervention (PCI)
in acute myocardial infarction (AMI) patients. Distal embolization/no-reflow
phenomena is one of the most dreaded complications in patients undergoing urgent
PCI for ST-segment elevation-myocardial infarction (STEMI). Unfortunately,
previous trials have failed to show a beneficial effect of these devices in AMI
patients.
The Protection of Distal Embolization in Acute
Myocardial Infarction (PREMIAR) trial was designed to assess the role of the
SpiderRX distal protection device (ev3, Inc., Minneapolis, Minnesota) to improve
myocardial reperfusion after primary or rescue angioplasty in high-risk patients
(defined as those with only baseline TIMI ≤ 2 coronary blood flow) with STEMI
within 12 hours of symptom onset.
Study Design
PREMIAR is a 1:1 open-label study that randomized
patients to either PCI plus stent and the SpiderRX system (n = 70) or PCI with
stent alone (n = 70). Patients underwent a first randomization according to the
use of glycoprotein IIb/IIIa inhibitors and the left anterior descending
coronary artery as the infarct-related artery. Patients who were excluded from
the study (baseline TIMI 3 flow, small vessel, bifurcation lesion, left main and
excessive tortuosity) were entered into a separate registry (n = 54).
Primary Endpoint: ST-segment resolution
Secondary Endpoints
- Major adverse cardiac events (death, heart failure,
or reinfarction)
- TIMI blush score
- Distal embolization or no reflow
- Ejection fraction
- Device success
Results
Baseline characteristics of patients enrolled in the
study were well balanced; use of the device was associated with a significantly
longer procedural time than patients in the control arm (Table).
Table. PREMIAR: Baseline Characteristics
| |
SpiderRX
(n = 70) |
Control
(n = 70) |
| Age (yrs) |
60 |
60 |
| Female (%) |
14 |
23 |
| Diabetes (%) |
19 |
20 |
| Killip class ≥ (%) |
26 |
19 |
| Baseline TIMI 0-1 flow (%) |
85 |
83 |
| LAD target (%) |
53 |
56 |
| GP IIb/IIIa (%) |
26 |
26 |
| Total procedural time (min)* |
52 |
44 |
*P < .001
GP = glycoprotein; LAD = left
anterior descending artery
Overall procedural device success was 94% and was higher
in patients with the LAD as the infarct-related artery than in patients treated
for a non-LAD lesion (97.3% vs 90.9%, respectively). Among all patients treated
with the device, 12% required predilatation, and in 48% of cases, macroscopic
debris was in the filter. Complete ST-segment resolution (> 70%) at 60 minutes
was identical in both study groups (60%) and by 240 minutes post-PCI, complete
ST-segment resolution was reached in < 70% of patients. The rate of angiographic
complications was also similar in both groups, with similar rates of distal
embolization and no-reflow phenomena (Figure 1). TIMI 3 blood flow and TIMI 3
blush score were also similar in the device and control groups (Figure 2).
Figure 1. PREMIAR: angiographic
complications.
Figure 2. PREMIAR: TIMI 3 blood flow and
TIMI blush score.
Clinical outcomes at 30 days and at 6 months, including
death, heart failure, and repeat revascularization procedures, were similar in
both groups. However, there was a significantly higher rate of reinfarction in
patients in the control arm (Figures 3 and 4).
Figure 3. PREMIAR: clinical events at 30
days.
Figure 4. PREMIAR: clinical events at 6
months.
Conclusions
- The use of the SpiderRX distal protection device is
safe and effective at retrieving atherothrombotic debris.
- The use of a filter-based protection device showed no
advantage in improvement of myocardial reperfusion.
- Better understanding of the role of the diverse
factors affecting myocardial reperfusion is needed in order to improve the
results of primary angioplasty.
Viewpoint
As with many of the other trials presented during this
session, PREMIAR was performed in a limited number of patients. The trial failed
to demonstrate a beneficial effect of using a distal filter protection system in
patients undergoing primary PCI in the acute phase of MI. Such results parallel
previous studies that assessed the impact of these devices in a thrombus-laden
artery and collectively demonstrate that there appears to be no benefit
regarding ST-segment resolution or no-reflow phenomena.
The reasons for such findings are likely multifactorial,
including the rather small number of patients studied, as well as our lack of
complete understanding of the factors involved in no-reflow/distal embolization
phenomena. Further research in this area may help us understand this complex
issue so that we can provide better treatment to these patients.
The research in this article was investigator-initiated
with research support from ev3, Inc. (Minneapolis, Minnesota).
RONDA: Renal Effects of Nesiritide During
Angiography
Luis Gruberg, MD, FACC
"These are disappointing results of this device and drug
combination. However, RONDA is a small study and the conclusions that can be
obtained are limited."
Presenter: Matthew J. Price, MD (Scripps Clinic, La
Jolla, California), for the RONDA Investigators
Contrast-induced nephropathy (CIN) is a strong predictor
of morbidity and mortality in patients who undergo percutaneous
cardiovascular/peripheral vascular interventions. Agents that prevent
vasoconstriction and increase glomerular filtration rate (GFR) may potentially
protect against CIN. Local intrarenal delivery of therapeutic agents may
increase the magnitude of renal effects while limiting adverse systemic effects
through renal first-pass elimination.
Nesiritide, a synthetic human brain natriuretic peptide
(BNP), has renal effects that could increase GFR and renal plasma flow, reduce
renal work by preventing sodium reabsorption, and inhibit the
rennin-angiotensin-aldosterone axis. However, its use at higher doses is
associated with systemic hypotension.
The Renal Effects of Nesiritide During Angiography
(RONDA) trial was designed to test the hypothesis that local renal-infusion of
nesiritide would improve renal function compared with intravenous nesiritide or
placebo during angiographic procedures. The trial assessed the beneficial effect
of intrarenal infusion with a dedicated renal infusion catheter (Benephit,
FlowMedica, Inc., Freemont, California) of nesiritide in patients considered to
be at high risk for CIN.
Study Design
A total of 41 patients with a creatinine clearance of <
80 mL/min and a systolic blood pressure > 120 mm Hg scheduled to undergo
catheterization were assigned to 1 of the 3 study arms:
- Intrarenal nesiritide injection (n = 13)
- Intravenous nesiritide injection (n = 15)
- Intravenous control arm (D/W 5%) (n = 13)
The study drug (0.02 mcg/kg/min) was administered 15
minutes prior to contrast and continued for a minimum of 30 minutes.
Primary endpoint: Percentage change from baseline
in BNP levels at 30 minutes
Secondary endpoints: Changes in GFR, renal plasma
flow, aldosterone levels, and blood pressure
Results
Patients were enrolled in the study at 2 centers in the
United States. Baseline characteristics of patients are shown in the Table.
Table. RONDA: Baseline Characteristics
| |
IR Nesiritide
(n = 12) |
IV Nesiritide
(n = 14) |
IV Control
(n = 12) |
| Age (yrs) |
72 |
73 |
72 |
| Female (%) |
15 |
16 |
17 |
| PVD (%) |
17 |
21 |
17 |
| Diabetes (%) |
50 |
43 |
42 |
| Hypertension (%) |
100 |
93 |
83 |
| Creatinine clearance (mL/min) |
57 |
53 |
51 |
| Serum creatinine (mg/dL) |
1.6 |
1.5 |
1.5 |
| Contrast volume (mL) |
258 |
227 |
233 |
| Study drug infusion time (HH:MM) |
1:16 |
1:10 |
1:19 |
IR = intrarenal; IV = intravenous; PVD =
peripheral vascular disease
Renal plasma flow increased in all 3 groups, but the
change was only significant in the intrarenal and intravenous active treatment
arm (P < .01) (Figure). Similarly, GFR increased significantly from baseline
during treatment (Figure).
Figure. RONDA: percent changes in renal
plasma flow and GFR from baseline to during treatment.
*All P values
relative to change from baseline.
In addition, in both nesiritide groups, BNP plasma
levels during treatment significantly increased from baseline (P < .001) and
were also significantly higher compared with control (P < .0001). BNP levels in
the intravenous nesiritide group trended higher than in the intrarenal arm, but
the difference was not significant (P = .06).
In the overall patient cohort, only 3 patients developed
CIN, including 1 in the intrarenal group and 2 in the intravenous active
treatment; there were no reports of CIN in the control arm. Furthermore, 6
patients in the active treatment groups required intravenous fluids due to
hypotension. There were no complications related to device use.
Conclusions
- Both intravenous and intrarenal nesiritide infusions
increased renal plasma flow and GFR during the procedure compared with
baseline levels.
- Intrarenal nesiritide appeared to have more potent
effects on GFR than intravenous treatment.
- Intrarenal nesiritide was not associated with
significantly lower systemic levels of BNP, suggesting that significant
renal clearance -- the basis of any potential benefit of targeted renal
therapy -- was overwhelmed at the dose used or does not occur with BNP.
- Low incidence of CIN in the study was likely due to
the fact that the patient population was at low risk for CIN.
- Given the greater renal clearance of fenoldopam and
the greater effects of IR fenoldopam on renal function, the agent may be a
better than nesiritide for studying targeted renal therapy for the
prevention of CIN in patients undergoing angiography.
Viewpoint
These are disappointing results of this device/drug
combination. Despite all of the preventive measures that were taken, 3 patients
still developed CIN, and they were in the active arms, not control.
Obviously, RONDA is a small study and the conclusions
that can be obtained are limited. Nevertheless, it seems that the investigators
believe that fenoldopam is a more appropriate drug and the ongoing Targeted
Intra-Renal Fenoldopam For Avoidance of Nephropathy (TIFFANY)[1]
study will help us understand whether this agent can prevent CIN.
Reference
- Price MJ, Garcia L, Davidson C, et al. Design and
rationale for the targeted intra-renal fenoldopam for avoidance of
nephropathy (TIFFANY) trial [abstract]. Am J Cardiol. 2005;96:117H.
SIMPLE II: Safety and Efficacy of the
Infinnium Paclitaxel-Eluting Stent
Luis Gruberg, MD, FACC
"All we can conclude from the SIMPLE II data is that the
use of this new (less expensive) drug-eluting stent appears to be safe and
effective in preventing restenosis. We will need more studies in order to really
appreciate the device's true potential."
Presenter: D.S. Gambhir, MD (Kailash Heart Institute,
Noida, India)
Despite the clinical and marketing success of the
various drug-eluting stents introduced to the market, economics still plays a
decisive role in the widespread use of these stents, especially in countries
outside the United States. The Safety and Efficacy of the Infinnium
Paclitaxel-Eluting Stent II (SIMPLE II) study is a prospective, multicenter
study that assessed the safety and efficacy of the Infinnium stent (Sahajanand
Medical Technologies, Surat, India) -- a less expensive, indigenously designed,
biodegradable, polymer, paclitaxel-eluting stent.
Primary Endpoints
- Safety: incidence of major adverse cardiac events
(MACE) (cardiac death, myocardial infarction, emergent cardiac surgery, and
clinically justified target lesion revascularization [TLR]) at 30 days
- Efficacy: angiographic binary restenosis rate at
6-month angiographic follow-up
Secondary Endpoints
Safety:
- Occurrence of MACE at 9 months
- Device-related serious adverse events at 9 months
- Angiographic stent thrombosis (subacute and late)
Efficacy:
- Acute gain, minimal lumen diameter, percent diameter
stenosis, late loss
- Angiographic success
- Procedural success
- Clinically justified TLR at 9 months
Results
SIMPLE II enrolled 103 patients at 3 centers (1 in
Brazil, 1 in India, and 1 in The Netherlands). Clinical and angiographic
follow-up is available for 101 patients (98%). Baseline clinical characteristics
are shown in Table 1.
Table 1. SIMPLE II: Baseline Characteristics
| |
(N = 103) |
| Age (yrs) |
59 |
| Female (%) |
29 |
| Diabetes (%) |
28 |
| Hypertension (%) |
62 |
| Hyperlipidemia (%) |
52 |
| Smoker (%) |
32 |
| S/P MI (%) |
39 |
| S/P PCI (%) |
6 |
| S/P CABG (%) |
2 |
CABG = coronary artery bypass graft; MI =
myocardial infarction; PCI = percutaneous coronary intervention; S/P =
status-post
Clinical outcomes at 30-day and 9-month follow-up were
favorable. At 30 days, there were no cardiac deaths and 3 cases of non-Q-wave
myocardial infarction. At 9-month follow-up, there was 1 case of late stent
thrombosis with a TLR rate of 1% (Table 2).
Table 2. SIMPLE II: Clinical Events at 270 Days
| Event |
(N = 103) |
| Cardiac death (%) |
1.0 |
| MI |
| Q-wave (%) |
1.0 |
| Non-Q-wave (%) |
2.9 |
| TLR |
| CABG (%) |
1.9 |
| Re-PCI (%) |
2.9 |
| Total MACE (%) |
9.7 |
| Stent thrombosis |
| Subacute (%) |
0.0 |
| Late (%) |
1.0 |
CABG = coronary artery bypass graft surgery;
MACE = major adverse cardiac events; MI = myocardial infarction; TLR =
target lesion revascularization
Angiographic follow-up at 6 months was available in 96
patients and showed a late loss of 0.38 ? 0.49 mm (Table 3). The binary in-stent
restenosis rate was 7.3% and the rate of in-segment restenosis was 8.3%.
Table 3. SIMPLE II: Angiographic Characteristics at
6-Month Follow-up
| Parameter |
(N = 96) |
| Stent length (mm) |
17.5 ? 4.1 |
| Reference vessel diameter (mm) |
2.68 ? 0.43 |
| Minimal lumen diameter (mm) |
2.02 ? 0.59 |
| In-stent late loss (mm) |
0.38 ? 0.49 |
| In-segment late loss (mm) |
0.18 ? 0.46 |
Conclusions
- The biodegradable polymer-based paclitaxel-eluting
Infinnium stent appears to be safe and effective in reducing restenosis at 6
months and is associated with an acceptable rate of cardiac events.
- Infinnium is the first indigenously designed and
evaluated, low-cost, drug-eluting stent from Asia to have obtained a CE
Quality Certificate for commercialization in Europe.
Viewpoint
The idea of a less expensive drug-eluting stent has been
around for some time now. India accepted the challenge and appears to have
succeeded in creating such a stent.
Due to time restraints imposed on the lecturers, very
few data were presented regarding some basic aspects of the stent, as well as
the polymer and the drug.
All we can conclude from the SIMPLE II data is that the
use of this new (less expensive) drug-eluting stent appears to be safe and
effective in preventing restenosis. These preliminary results suggests that the
Infinnium stent may provide comparable results to those seen with currently
available paclitaxel-eluting stents. We will need more studies in order to
really appreciate the device's true potential.
Authors and Disclosures
Author
Luis Gruberg, MD, FACC
 |
Interim Director, Division of Invasive
Cardiology, Rambam Medical Center, Haifa, Israel
Disclosure: Luis
Gruberg, MD, has disclosed no relevant financial relationships.
|
Editor
David Good
Editorial Director, Medscape Cardiology
Disclosure: David Good has disclosed no relevant financial
relationships.
|
Ariana Del Negro
Associate Editorial Director, Medscape Cardiology
Disclosure: Ariana Del Negro has disclosed no relevant financial
relationships.
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