(Circulation. 2000;101:955.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Randomized Trial Comparing Intravenous Nitroglycerin and Heparin for Treatment of Unstable Angina Secondary to Restenosis After Coronary Artery Angioplasty
From the Cardiac Catheterization Laboratory and Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada.
Correspondence to Serge Doucet, MD, Research Centre, Montreal Heart Institute, 5000 Bélanger St E, Montreal, Quebec, Canada H1T 1C8.
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Abstract |
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Background—The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina.
Methods and Results—We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63±30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4.3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1.73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction.
Conclusions—Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.
Key Words: angina • restenosis • nitroglycerin • heparin • ischemia
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Introduction |
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The central role of an active atheromatous plaque in the pathophysiological substrate of unstable angina is well recognized.1 2 3 Flow reductions causing acute ischemia are mainly due to platelet aggregation and thrombus formation on ulcerated plaques and active vasoconstriction,4 mediated by such substances as serotonin, thromboxane A2, thrombin, and endothelin.5 6 Unstable angina may also involve a systemic procoagulant state with increased proaggregant platelet activity and decreased fibrinolytic activity.5 Accordingly, anticoagulant therapy with heparin and antiplatelet therapy with aspirin7 8 9 10 or glycoprotein IIb/IIIa receptor antagonists11 12 13 are effective to prevent complications in unstable angina.
Restenosis after PTCA remains a major limitation, occurring in 25% to 45% of dilated lesions.14 Symptomatic restenosis usually presents within 3 months of the procedure.15 The presenting symptom in most cases is exertional angina, but unstable angina occurs in up to 41% of patients16 and in 68% of patients whose PTCA was initially performed for rest angina.16
Neointima formation caused by smooth muscle cell proliferation and extracellular matrix production is a prominent feature in restenotic lesions.17 Angioscopy in patients with restenosis commonly reveals white, nonpigmented, smooth, and fibrotic lesions, in contrast to the yellow or brown pigmentation observed in primary nonrestenotic lesions.18 19 One report of angioscopic findings in 4 patients with unstable angina after PTCA described white, unpigmented lesions with intracoronary mural thrombi firmly attached to the wall of the artery,18 contrasting with the lining, or protruding white thrombus and unstable plaques, often ulcerated, in nonrestenotic unstable angina.19 20 Various authors have shown an association between coronary vasoconstriction and restenosis,21 22 23 and unpublished data from our laboratory indicate increased vasoreactivity to acetylcholine at PTCA sites in the 6 months after the procedure. These findings, along with the favorable prognosis of unstable angina associated with restenosis, suggest different pathophysiological mechanisms compared with classic unstable angina. The differences are also reflected in a different clinical course of unsuccessfully treated unstable angina associated with restenosis versus the classic form: in the latter, death and myocardial infarction are the main complications, whereas in post-PTCA cases, refractory angina is the major problem.
On the basis of the importance of smooth muscle cell proliferation and increased vasoreactivity in unstable angina secondary to restenosis, we speculated that intravenous nitroglycerin might be particularly effective in preventing recurrent ischemia and that heparin might be less useful, considering the rarity of more severe thrombotic complications (myocardial infarction and death) in this setting. This study was therefore designed as a 2x2 factorial double-blind, placebo-controlled, randomized trial comparing intravenous nitroglycerin, heparin, a combination of the 2, or neither in the treatment of unstable angina secondary to restenosis.
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Methods |
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Patient Population
All patients admitted to the Montreal Heart Institute with a diagnosis of unstable angina within 2 weeks to 6 months after coronary angioplasty were considered for the study. The 2-week asymptomatic period was necessary to exclude patients with poor initial angioplasty results and the 6-month upper limit to exclude patients more likely to show progression in native coronary disease than restenosis.24 25 Unstable angina was defined as recurrent or increased frequency of chest pain lasting >5 minutes at rest or with minimal exertion within 24 hours before randomization. In the absence of ischemic ECG changes (>1 mm ST-segment depression or new T-wave abnormalities), inclusion required independent confirmation of the diagnosis of unstable angina by 2 cardiologists.
Exclusion criteria included vein or internal mammary artery bypass
graft as the target lesion, ST-segment elevation lasting 
30 minutes,
indication for thrombolytic treatment, new Q wave on
the postangioplasty ECG, stent implantation or atherectomy during the
last procedure, contraindication to heparin or
nitroglycerin, bypass surgery within the previous 6
months, previous participation in the trial, or medical
contraindication to repeated angiography and/or angioplasty. The
protocol was approved by the Institutional Review Board, and all
patients signed an informed consent form. Recruitment began November
25, 1993, and ended on July 20, 1996.
Study Medication and Protocol
The trial medications were prepared and coded for each patient
by the hospital pharmacist. The 4 treatment groups were (1)
intravenous nitroglycerin infusion plus
placebo heparin, (2) intravenous heparin 5000 U bolus
followed by infusion at 1000 U/h (1200 U/h for patients weighing 80
kg) plus placebo nitroglycerin, (3)
intravenous nitroglycerin plus
intravenous heparin, and (4) placebo
nitroglycerin plus placebo heparin.
Intravenous nitroglycerin/placebo was diluted in 5% dextrose in water and infused at an initial rate of 50 µg/min. If well tolerated, the infusion rate was increased by 25 µg/min every 12 hours to overcome nitrate tolerance. When headache occurred, acetaminophen (325 to 650 mg every 6 hours) was given, and the nitroglycerin/placebo infusion was decreased by 10 µg/min. The infusion rate was lowered by 10 µg/min for systolic pressure <100 mm Hg and was temporarily interrupted for pressure <80 mm Hg. The heparin infusion rate was adjusted according to the activated partial thromboplastin time (aPTT). aPTT results were known only to the pharmacist, who modified the infusion rate according to a predefined algorithm to maintain the aPTT at 1.5 to 2 times control values. Infusion rates of placebo solutions were also modified to maintain blinding. Recurrent chest pain was treated with sublingual nitroglycerin (0.4 to 0.8 mg) followed by an increase of the nitroglycerin/placebo infusion by 25 µg/min. An acceleration of symptoms despite treatment was an indication for urgent catheterization or administration of open-label heparin and nitroglycerin, without unblinding.
Aspirin (325 mg/d) was given to all patients. ß-Blockers or calcium antagonists were allowed, but the use of open-label nitroglycerin and any nitrate preparation was prohibited (except for patients with accelerated symptoms, as described in the preceding paragraph). Only 2 patients were receiving long-acting nitrates at the time of randomization. ECGs were obtained before randomization, daily thereafter, and whenever chest pain occurred. Creatine kinase and MB fraction were measured before randomization, every 6 hours for 24 hours, and daily until coronary angiography. A coronary angiogram was performed 48 to 96 hours after randomization or earlier if clinically required. Study medications were stopped just before angiography, marking the end of the trial and the time for collection of end-point data. After administration of 2000 U heparin and of intracoronary nitroglycerin (0.3 mg), multiple orthogonal views of the previously dilated coronary segment were obtained. Quantitative angiographic measurements in the single projection showing the most severe stenosis were made by experienced cardiovascular radiologists blinded to treatment assignment.
End Points
Recurrence of angina was the primary end point of the
trial, because unstable angina associated with restenosis
rarely results in myocardial infarction or death but has a high rate of
recurrent symptoms.16 24 Angina was classified as class 1
in the absence of ECG changes, class 2 when accompanied by transient
ST-T changes, class 3 when lasting 20 minutes with ST-T changes, and
class 4 when refractory to medical management and requiring
administration of open-label nitroglycerin and heparin
or urgent angiography.
Statistical Analysis
On the basis of an expected 50% rate of recurrent angina, 200
patients were necessary to detect a 40% risk reduction at a power of
80% with a 2-tailed 
-value of 0.05. All events were classified
before unblinding. Baseline characteristics were compared by
t-test and 
2 statistics. Event
rates were compared by 2-tailed 2 statistics,
odds ratios, and 95% confidence limits. Logistic regression
analysis was used to test potential interactions between
treatments. Results were analyzed by the intention-to-treat
principle.
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Results |
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The study population included 11% (200 of 1810) of all patients who had angiography at the Montreal Heart Institute because of recurrent chest pain after angioplasty during the recruitment period. Of the 1810 patients, 1176, or 65%, had exertional angina and were excluded. Of the 634 remaining patients with unstable angina, 434 had exclusion criteria or were initially admitted to another institution, precluding their participation in the trial. Selected baseline characteristics of the study groups are shown in Tables 1
and 2. No significant differences were
observed. Protocol deviations were noted in 9 patients. The study
medication was started >24 hours after the most recent episode of
chest pain in 2 patients. Repeat angiography was not performed in 2
patients (1 patient referred to surgery and the other treated
medically). One patient had had a stent implanted at the previous
angioplasty, and the target lesion was a vein graft in one. The study
drug was discontinued prematurely in 2 patients who refused continued
participation in the trial, and 1 patient was included in the trial
twice during different hospitalizations. Of the patients with protocol
violations, 3 were in the nitroglycerin-alone group, 2
in the heparin group, 2 in the combination group, and 2 in the placebo
group. The results were unchanged by inclusion or exclusion of these
patients.
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Of the 191 remaining patients, 157 (83%) had angiographic
restenosis (50% by quantitative angiography). Of the 34
patients without restenosis, 11 (5.6%) had a new
stenosis 50% in a coronary artery segment different
from the one that had been dilated. The patients without
restenosis were equally distributed among the 4 study groups.
Use of concomitant oral medication was comparable among treatment
groups.
End Points
Recurrence of angina was observed in 112 patients
(58.6%): class 1, 29.8%; class 2, 7.3%; class 3, 6.3%; and
class 4 (refractory angina), 15.2%. The distribution of
different angina classes for each treatment group is provided in Table 3.
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Recurrent angina occurred in 42.6% of patients treated with
nitroglycerin alone, 41.7% of patients treated with
nitroglycerin plus heparin, 75% of patients treated
with heparin alone, and 75% of patients receiving placebo
(P<0.003 for nitroglycerin alone and for
nitroglycerin plus heparin versus placebo, Figure 1A). Refractory angina (class 4) occurred
in 2 of 47 patients (4.3%) for nitroglycerin, 2 of 48
patients (4.2%) for combined treatment, 14 of 48 patients (29.2%) for
heparin, and 11 of 48 patients (22.9%) for placebo
(P<0.002 for nitroglycerin and
nitroglycerin plus heparin versus placebo, Figure 1B). No interaction was detected between
nitroglycerin and heparin effects by logistic
regression (P=0.954 for recurrent angina and
P=0.757 for class 4 refractory angina). In the absence of
interaction, the factorial design permits analysis of all
patients receiving nitroglycerin versus those treated
with nitroglycerin placebo. The combined
analysis, shown in Figure 2, indicates a highly significant difference in outcome by presence or
absence of nitroglycerin therapy but no difference for
heparin. The odds of recurrent angina for nitroglycerin
versus no nitroglycerin was 0.24 (95% CI, 0.13 to
0.45, P=0.0001) and for heparin versus no heparin, 0.98
(95% CI, 0.55 to 1.73, P=NS). The results were unchanged by
multivariate analyses controlling for all
variables included in Tables 1
and 2. There were no
deaths or myocardial infarctions in the study. Complications and side
effects were relatively infrequent (Table 4).
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Of the patients with protocol violations, 2 of the 5 receiving
nitroglycerin and 3 of the 4 without
nitroglycerin had recurrent angina. Inclusion of these
patients did not change the results, with recurrent angina in 40% of
patients with nitroglycerin alone, 44% with combined
nitroglycerin and heparin treatment, 76% with heparin
alone, and 74% with placebo (P<0.0001). Results were also
analyzed by severity of restenosis, with severe
stenosis defined as 70%. The recurrent angina rate with
nitroglycerin therapy was 32% in the 53 patients with
restenotic lesions <70% and 56% in 34 patients with
restenotic lesions 70%. In the group that did not receive
nitroglycerin, 74% of the 57 patients with no severe
restenosis and 71% of 28 patients with severe
restenosis had recurrent angina. In a
multivariate logistic regression including the severity
of the restenosis, nitroglycerin use remained
highly predictive of absence of angina (P=0.0003), with odds
of 0.17 (95% CI, -0.07 to 0.38) for recurrent angina in patients with
severe restenosis and of 0.51 (95% CI, -0.18 to 1.47) for
patients whose restenosis was not severe (P=0.11 for
<70% versus 70%).
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Discussion |
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In the present study, the administration of intravenous nitroglycerin markedly reduced the occurrence of angina and the severity of recurrent angina among patients hospitalized for unstable angina within 6 months of coronary angioplasty. Heparin alone showed no such benefit, and the addition of heparin to nitroglycerin did not improve treatment efficacy.
Comparison With Previous Findings in the Literature
The accepted standard therapy for unstable angina has been aspirin
and heparin.26 The pathophysiological
mechanism of ischemia in unstable angina unrelated to PTCA is a
primary reduction in myocardial oxygen supply by thrombosis and
vasoconstriction superimposed on a plaque erosion or
fissure.1 2 3 The thrombus is usually labile and results in
transient vascular occlusion, often lasting only 10 to 20 minutes. The
waxing and waning of platelet thrombus formation at this active
plaque site, with or without abnormal vasomotion, accounts for the
spontaneous variability of symptoms during the acute phase of unstable
angina and the potential for later recurrence of
ischemic symptoms.1 2 3 4 5 6 The efficacy of
antiplatelet and anticoagulant drugs is thus related to specific
control of the underlying pathophysiological
mechanisms; intravenous nitroglycerin is
also recommended in some patients, although data from clinical trials
are few and not well controlled.3 27 28
No comparative studies exist on the efficacy of medical therapy in patients with unstable angina within 6 months of PTCA. Common clinical practice is to apply the same medical therapy as for other patients with this diagnosis, specifically heparin and aspirin, and to perform coronary angiography and angioplasty to relieve the recurrent obstruction. The present study showed that nitroglycerin was very effective in preventing symptoms due to recurrent ischemia in such patients, whereas heparin was not.
Potential Implications
The clinical pattern and the timing of presentation
are important predictors of restenosis when a patient returns
with chest pain after PTCA.29 Patients presenting with
unstable angina after angioplasty are at very high risk of having
angiographic restenosis, consistent with our
angiographic findings. The rate of recurrent angina was high in our
patients and was strongly reduced by intravenous nitrates
(from 75% in the placebo/heparin groups to 42% in the
nitrate/combined groups). The effect on refractory angina was even more
striking, reaching an 85% reduction with nitroglycerin
(decreasing from 26% in the no-nitroglycerin groups to
4% in the nitroglycerin groups). These findings
suggest that intravenous nitroglycerin may
have a particularly useful role to play in the treatment of patients
with unstable angina within 6 months of PTCA. Conversely, the lack of
efficacy of heparin in these patients and the low rate of serious
complications suggest that routine heparin therapy is not indicated
and, indeed, that hospitalization in a coronary care unit
environment may not be necessary.
Our observations have potential pathophysiological implications. The superior efficacy of nitroglycerin compared with heparin therapy in preventing recurrent ischemic events points to a primary role of abnormalities in coronary vasoreactivity, rather than thrombosis, in patients with unstable angina due to restenosis after PTCA, consistent with previous observations in the literature.18 21 22 23 In view of the apparently important role of coronary vasoconstriction, some patients with borderline lesions may be managed with nitrates (assuming that this vasospastic phase is only transient); repeat angioplasty may occasionally not be necessary. Another potential approach could be the systematic use of nitrate therapy after coronary angioplasty. Given the fact that spontaneous regression of mild restenotic lesions over time has been observed,30 nitrates or other coronary vasodilators could help to overcome the period of exaggerated and abnormal vasoreactivity and allow stabilization and better healing of the restenotic plaque in the first 6 months after angioplasty. This strategy might avoid unnecessary invasive procedures, prevent a "restenosis cycle," and result in significant cost savings. Because restenosis remains a major drawback of coronary angioplasty, even with the widespread use of stents,31 new avenues to lower the need for reintervention are desirable, and further study of this approach is warranted.
Study Limitations
The diagnosis of unstable angina is partly subjective and the end
point of recurrent pain relatively soft. Transient
diagnostic ST-T changes were not required for enrollment,
because many patients presenting with unstable angina due to
restenosis fail to show ECG changes.
Nitroglycerin was more effective in preventing episodes
of chest pain associated with ischemic ST segment changes and
more severe ischemic episodes requiring urgent intervention.
The lesser efficacy of nitroglycerin among patients
without ECG abnormalities may have been due to dilution by patients
with nonischemic chest pain.
We found that nitroglycerin was associated with greater efficacy in patients with less severe angiographic restenosis (stenoses <70%). It is tempting to speculate that these patients had a more important vasoconstrictive component to their symptoms, accounting for the greater efficacy of nitroglycerin. However, before we conclude that nitroglycerin has more benefit for patients with less severe restenotic lesions because symptoms due to such lesions involve a larger element of vasospasm, it should be remembered that all angiograms were obtained after intracoronary nitroglycerin administration. Thus, these lesions may have appeared less severe at angiography because they were more responsive to nitroglycerin, explaining the greater benefit.
It is uncertain whether our results can be extrapolated to patients with in-stent restenosis causing unstable angina. Recent studies, particularly serial intravascular ultrasound observations,32 have demonstrated that the mechanism of restenosis after angioplasty without a stent involves not only neointimal hyperplasia but also chronic geometric remodeling of the treatment site. Conversely, restenosis after stent implantation seems to be caused purely by stent-related increases in cellular proliferation.33 If increased vasoreactivity and smooth muscle cell proliferation explain the efficacy of intravenous nitroglycerin in unstable angina after angioplasty, in-stent restenosis should also be responsive to nitroglycerin. An appropriately designed clinical trial including patients with in-stent restenosis is needed to resolve this important issue. For the moment, it should be kept in mind that unstable angina early after stent implantation may be due to stent thrombosis, for which intravenous heparin may constitute an important part of the therapy. This complication usually occurs in the first 2 weeks after angioplasty.
Another point to remember is that unstable angina after PTCA is not a
monolithic entity. Although most cases are related to
restenosis, some may occur in association with new severe
coronary artery lesions and might therefore display a
pathophysiology more similar to classic unstable angina. Such patients
may benefit from heparin therapy. Prolonged rest pain and
presentation >3 months after angioplasty might help
identify such individuals. In our trial, only 11 patients (5.7% of the
study population) had a new stenosis of 50% in another
coronary segment.
It can be concluded from our study that intravenous nitroglycerin is highly effective to prevent recurrent angina and refractory angina requiring urgent intervention in patients with unstable angina in the 6 months after PTCA, whereas heparin has no benefit. This patient population constitutes a low-risk subgroup in which the antithrombotic therapy used for classic unstable angina is not usually needed. These observations have significant practical implications for the management of patients presenting with unstable angina after coronary artery angioplasty.
Received July 23, 1999; revision received September 14, 1999; accepted September 29, 1999.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Théroux P, Fuster V. Acute coronary
syndromes: unstable angina and non–Q-wave myocardial infarction.
Circulation. 1998;97:1195–1206.
[Free Full Text]
-
Ribeiro PA, Shah PM. Unstable angina: new insights
into pathophysiologic characteristics, prognosis, and management
strategies. Curr Probl Cardiol.. 1996;21:669–731.[Medline]
[Order article via Infotrieve]
-
Cairns J, Théroux P, Armstrong P, Bogaty P,
Kells C, Thompson C, Warnica W. Unstable angina: report from a Canadian
expert roundtable. Can J Cardiol. 1996;12:1279–1292.[Medline]
[Order article via Infotrieve]
-
Bogaty P, Hackett D, Davies G, Maseri A.
Vasoreactivity of the culprit lesion in unstable angina.
Circulation. 1994;90:5–11.
[Abstract/Free Full Text]
-
Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM.
Specific platelet mediators and unstable coronary artery
lesions: experimental evidence and potential clinical implications.
Circulation. 1989;80:198–205.
[Abstract/Free Full Text]
-
Fuster V, Badimon L, Badimon JJ, Chesebro JH. The
pathogenesis of coronary artery disease and the acute
coronary syndromes. N Engl J Med. 1992;326:242–250.[Medline]
[Order article via Infotrieve]
-
Théroux P, Ouimet H, McCans J, Latour JG, Joly
P, Lévy G, Pelletier E, Juneau M, Stasiak J, de Guise P,
Pelletier GB, Rinzler D, Waters DD. Aspirin, heparin, or both to treat
acute unstable angina. N Engl J Med. 1988;319:1105–1111.[Abstract]
-
Cohen M, Adams PC, Parry G, Xiong J, Chamberlain D,
Wieczorek I, Fox KAA, Chesebro JH, Strain J, Keller C, Kelly A,
Lancaster G, Ali J, Kronmal R, Fuster B. Combination antithrombotic
therapy in unstable rest angina and non–Q-wave infarction in nonprior
aspirin users. Circulation. 1994;89:81–88.
[Abstract/Free Full Text]
-
The RISC Group. Risk of myocardial infarction and
death during treatment with low dose aspirin and
intravenous heparin in men with unstable coronary
artery disease. Lancet. 1990;336:827–830.[Medline]
[Order article via Infotrieve]
-
Neri-Serneri GG, Rovelli F, Gensini GF, Pirelli S,
Carnovali M, Fortini A. Effectiveness of low-dose heparin in prevention
of myocardial infarction. Lancet. 1987;1:937–942.[Medline]
[Order article via Infotrieve]
-
The Platelet Receptor Inhibition in
Ischemic Syndrome Management in Patients Limited by Unstable
Signs and Symptoms (PRISM-PLUS) Study Investigators. Inhibition of the
platelet glycoprotein IIb/IIIa receptor with tirofiban
in unstable angina and non-Q-wave myocardial infarction. N
Engl J Med. 1998;338:1488–1497.
[Abstract/Free Full Text]
-
The PURSUIT Trial Investigators. Inhibition of
platelet glycoprotein IIb/IIIa with eptifibatide in
patients with acute coronary syndromes. N Engl
J Med. 1998;339:436–443.
[Abstract/Free Full Text]
-
The CAPTURE Investigators. Randomised
placebo-controlled trial of abciximab before and during
coronary intervention in refractory unstable angina: the
CAPTURE study. Lancet. 1997;349:1429–1435.[Medline]
[Order article via Infotrieve]
-
Landzberg BR, Frishman WH, Lerrick K. Pathophysiology
and pharmacological approaches for prevention of coronary
artery restenosis following coronary artery balloon
angioplasty and related procedures. Prog Cardiovasc Dis. 1997;39:361–398.[Medline]
[Order article via Infotrieve]
-
Serruys PW, Luijten HE, Beatt KJ, Geuskens R, De Feyter
PJ, van den Brand M, Reiber JHC, ten Katen HJ, van Es GA, Hugenholtz
PG. Incidence of restenosis after successful coronary
angioplasty: a time-related phenomenon. Circulation.. 1988;77:361–371.
[Abstract/Free Full Text]
-
Levine GN, Chodos AP, Loscalzo J. Restenosis
following coronary angioplasty: clinical
presentations and therapeutic options. Clin
Cardiol. 1995;18:693–703.[Medline]
[Order article via Infotrieve]
-
Garratt KN, Edwards WD, Kaufmann UP, Vlietstra RE,
Holmes DR Jr. Differential histopathology of primary atherosclerotic
and restenotic lesions in coronary arteries and
saphenous vein bypass grafts: analysis of tissue obtained from
73 patients by directional atherectomy. J Am Coll
Cardiol. 1991;17:442–448.[Abstract]
-
Ramee SR, White CJ, Collins TJ, Mesa JE, Murgo JP.
Percutaneous angioscopy during coronary
angioplasty using a steerable microangioscope. J Am Coll
Cardiol. 1991;17:100–105.[Abstract]
-
Bauters C, Lablanche JM, Renaud N, McFadden EP, Hamon
M, Bertrand ME. Morphological changes after
percutaneous transluminal coronary angioplasty
of unstable plaques: insights from serial angioscopic follow-up.
Eur Heart J. 1996;17:1554–1559.
[Abstract/Free Full Text]
-
Silva JA, Escobar A, Collins TJ, Ramee SR, White CJ.
Unstable angina: a comparison of angioscopic findings between diabetic
and nondiabetic patients. Circulation. 1995;92:1731–1736.
[Abstract/Free Full Text]
-
Bertrand ME, Lablanche JM, Thieuleux FA, Fourrier JL,
Traisnel G, Asseman P. Comparative results of
percutaneous transluminal coronary angioplasty
in patients with dynamic versus fixed coronary
stenosis. J Am Coll Cardiol. 1986;8:504–508.[Abstract]
-
Bertrand ME, Lablanche JM, Fourrier JL, Gommeaux A,
Ruel M. Relation to restenosis after
percutaneous transluminal coronary angioplasty
to vasomotion of the dilated coronary arterial
segment. Am J Cardiol. 1989;63:277–281.[Medline]
[Order article via Infotrieve]
-
Leisch F, Harringer W, Kerschner K, Hofmann R,
Feirer G, Schützenberger W. Importance of
coronary spasm for recurrences following
percutaneous transluminal coronary angioplasty
(PTCA). Eur Heart J. 1991;12:1029–1033.
-
Rosen DR, Cannon RO, Watson RM, Bonow RO, Mincemoyer R,
Ewels C, Leon MB, Lakatos E, Epstein SE, Kent KM. Three year anatomic,
functional and clinical follow-up after successful
percutaneous transluminal coronary angioplasty.
J Am Coll Cardiol. 1987;9:1–7.[Abstract]
-
Stone GW, Ligon RW, Rutherford BD, McConahay DR,
Hartzler GO. Short-term outcome and long-term follow-up following
coronary angioplasty in the young patient: an 8-year
experience. Am Heart J. 1989;118:873–877.[Medline]
[Order article via Infotrieve]
-
Oler A, Whooley MA, Oler J, Grady D. Adding heparin to
aspirin reduces the incidence of myocardial infarction and death in
patients with unstable angina: a meta-analysis.
JAMA. 1996;276:811–815.[Abstract]
-
Curfman GD, Heinsimer JA, Lozner EC, Fung HL.
Intravenous nitroglycerin in the treatment
of spontaneous angina pectoris: a prospective, randomized trial.
Circulation. 1983;67:276–282.
[Abstract/Free Full Text]
-
Kaplan K, Davison R, Parker M, Przbylek J, Teagarden
JR, Lesch M. Intravenous nitroglycerin for
the treatment of angina at rest unresponsive to standard nitrate
therapy. Am J Cardiol. 1983;51:694–698.[Medline]
[Order article via Infotrieve]
-
Weintraub WS, Kosinski AS, Brown CL III, King SB III.
Can restenosis after coronary angioplasty be predicted
from clinical variables? J Am Coll Cardiol. 1993;21:6–14.[Abstract]
-
Mehta VY, Jorgensen MB, Raizner AE, Wolde-Tsadik G,
Mahrer PR, Mansukhani P. Spontaneous regression of restenosis:
an angiographic study. J Am Coll Cardiol. 1995;26:696–702.[Abstract]
-
Fischman DL, Leon MB, Baim DS, Schatz R, Savage MP,
Penn I, Detre K, Veltri L, Ricci D, Nobuyhoshi M, Cleman M, Heuser R,
Almond D, Teirstein PS, Fish D, Colombo A, Brinker J, Moses J,
Shaknovich A, Hirshfeld J, Bailey S, Ellis S, Rake R, Goldberg S, for
the Stent Restenosis Study Investigators. A randomized
comparison of coronary-stent placement and balloon angioplasty
in the treatment of coronary artery disease. N Engl
J Med. 1994;331:496–501.
[Abstract/Free Full Text]
-
Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF,
Wong SC, Hong MK, Kounch JR, Leon MB. Arterial remodeling
after coronary angioplasty: a serial intravascular ultrasound
study. Circulation. 1996;94:35–43.
[Abstract/Free Full Text]
-
Hoffmann R, Mintz GS, Dussaillant GR, Popma JJ, Pichard
AD, Satler LF, Kent KM, Griffin J, Leon MB. Patterns and mechanisms of
in-stent restenosis: a serial intravascular ultrasound study.
Circulation. 1996;94:1247–1254.
[Abstract/Free Full Text]
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  P. A. Lemos, P. W. Serruys, and J. E. Sousa Drug-Eluting Stents: Cost Versus Clinical Benefit Circulation, June 24, 2003; 107(24): 3003 - 3007. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Chandrasekar, S. Nattel, and J.-F. Tanguay Coronary artery endothelial protection after local delivery of 17{beta}-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1570 - 1576. [Abstract] [Full Text] [PDF]
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|
|
 |
|
 J. Hirsh, S. S. Anand, J. L. Halperin, and V. Fuster Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association Arterioscler. Thromb. Vasc. Biol., July 1, 2001; 21 (7): e9 - e9. [Full Text] [PDF]
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|
|
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|
J. Hirsh, S. S. Anand, J. L. Halperin, and V. Fuster Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association Circulation, June 19, 2001; 103(24): 2994 - 3018. [Full Text] [PDF]
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|
 Nitroglycerin for Unstable Angina Due to Restenosis Journal Watch Cardiology, March 31, 2000; 2000(331): 7 - 7. [Full Text]
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