First author,
Year,
Country [ref]
Study
design,
duration of
FU
Volzke, 2000,
Germany [27]
cohort
6 months
Yoshida, 1999,
Japan [28]
Cohort description [No of patients (M/F),
Ethnicity, Mean Age (SD), inclusion
criteria]
Outcome
assessed
(diagnostic
criteria)*
[Classification of
outcome]
Intervention
Gene-gene
interaction
assessed?
(gene)
Quality
score
Main Findings [Calculated OR
(95% Confidence Interval) or
presentation of results when
data where not available for
OR calculation]
Balloon
Angioplasty
PTCA-balloon
No
35
Data synthesized in the metaanalysis
Restenosis (2)
[surrogate]
PTCA-balloon
No
30
Data synthesized in the metaanalysis
Restenosis (1)
[surrogate]
cohort
5.21 (3.9)
years
cohort
6 months
511 (388/123), Eur Whites, 60.6 (8.6), CAD
patients undergoing elective PTCA of a
previously untreated native coronary artery
123 (nr), East Asians, 58.2 (10.2), MI
patients undergoing PTCA discharged from
hospital at the start of FU
69 (57/12), Eur Whites, 58 (9.9), UA patients
undergoing PTCA
Restenosis (3)
[surrogate]
PTCA-balloon
No
27
Data synthesized in the metaanalysis
Kamitani,
1995, Japan
[30]
Samani, 1995,
UK [31]
cohort
6 months
103 (103/00), East Asians, 52 (1), Pimary
PTCA for MI patients
Restenosis (1)
[surrogate]
PTCA-balloon
No
27
Data synthesized in the metaanalysis
cohort
4 months
Restenosis (1)
[surrogate]
PTCA-balloon
No
34
Data synthesized in the metaanalysis
van
Bockxmeer,
1995, Australia
[32]
Tsukada, 1997,
Japan [33]
cohort
6 months
233 (194/39), nr, 56 (1), single-vessel PTCA
in the Subcutaneous Heparin and Angioplasty
Restenosis Prevention (SHARP) study
207 (170/37), Eur Whites, 57 (9), CAD
patients undergoing elective PTCA
Restenosis (1)
[surrogate]
PTCA-balloon
Yes (APOE)
33
Data synthesized in the metaanalysis
cohort
3 months
96 (nr), East Asians, 60 (1.0), CAD patients
undergoing elective PTCA
Restenosis (3)
[surrogate]
PTCA-balloon
No
28
Data synthesized in the metaanalysis
Beohar, 1995,
USA [34]
cohort
3 months
89 (nr), Am Whites, 63.9 (10), CAD patients
undergoing elective PTCA
Restenosis (3)
[surrogate]
PTCA-balloon
No
24
Data synthesized in the metaanalysis
Zee, 2001,
Spain [35]
cohort
6 months
342 (305/37), Eur Whites, 58.9 (9.6), CAD
patients undergoing PTCA
Restenosis (1)
[surrogate]
PTCA-balloon
No
37
Data synthesized in the metaanalysis
Ohishi, 1993,
Japan [36]
cohort
6 months
82 (nr), East Asians, nr, MI patients
undergoing primary PTCA
Restenosis (1)
[surrogate]
PTCA-balloon
No
23
Data synthesized in the metaanalysis
Kasi, 1996,
Spain [29]
Hertwig, 2002,
Germany [37]
cohort
4-6 months
145 (128/17), Eur Whites, 59.2 (8.4), CAD
patients undergoing repeat PTCA for
restenotic lesions at FU angiography
52 (47/5), Eur Whites, nr, CAD patients
undergoing PTCA
Recurrent
Restenosis (1)
[surrogate]
endothelial
dysfunction (4)
[surrogate]
PTCA-balloon
No
33
Mulder, 2003,
Netherlands
[38]
crosssectional
(PREFACE)
Wijpkema,
2006,
Netherlands
[39]
Gomma, 2002,
UK [40]
cohort
9 months
2888 (2050/838), Eur Whites, 62 (11), CAD
patients undergoing elective PTCA
Restenosis (5)
[clinical]
cohort
6 months
205 (155/50), Eur Whites, 59.4 (9.9), CAD
patients undergoing PTCA
Restenosis (3)
[surrogate]
PTCA-STENT
Ruy, 2002,
Korea [41]
cohort
6 months
238 (178/60), East Asians, 59.5 (9.9), CAD
patients undergoing PTCA
Restenosis (3)
[surrogate]
Ribichini,
2004, Italy
[42]
Taniguchi,
2001, Japan
[43]
Koch, 2000,
Germany [44]
cohort
6 months
897 (160/737), Eur Whites, 61 (10), CAD
patients undergoing PTCA
cohort
6 months
Allele contrast OR=1.24 (0.8-2.0)
Domin model OR=1.79 (0.8-4.2)
Recess model OR=0.90 (0.4-2.1)
an ameliorating effect of
pravastatin in patients with the
DD genotype was found
PTCA-balloon
+ Pravastatin
(40mg)
Angioplasty
with stent
deployment
PTCA-STENT
No
23
Yes (AGT,
AGT1R,
AGT2R,
HMOX1)
No
35
Data synthesized in the metaanalysis
27
Data synthesized in the metaanalysis
PTCA-STENT
Yes
(CYP11B2 ,
AGT)
32
Restenosis (3)
[surrogate]
PTCA-STENT
No
33
Data synthesized in the metaanalysis
No significant gene-gene
interaction was observed
Data synthesized in the metaanalysis
67 (50/17), East Asians, 65.2 (9.7), CAD
patients undergoing PTCA
Restenosis (1)
[surrogate]
PTCA-STENT
No
23
Data synthesized in the metaanalysis
cohort
1 year
1850 (1458/392), Eur Whites, 62.9 (10),
CAD patients undergoing PTCA
Restenosis (3)
[surrogate]
PTCA-STENT
No
40
Data synthesized in the metaanalysis
Gurlek, 2000,
Turkey [45]
cohort
6 months
132 (112/20), Turks, 53 (9), CAD patients
undergoing PTCA
Restenosis (3)
[surrogate]
PTCA-STENT
No
29
Data synthesized in the metaanalysis
Hamon, 1998,
France [46]
cohort
6 months
271 (229/42), Eur Whites, 60 (10), CAD
patients undergoing PTCA
Restenosis (3)
[surrogate]
PTCA-STENT
Yes (AGT1R)
34
Hamon, 1996
France [47]
cohort
nr
291 (nr), Eur Whites, nr, CAD patients
undergoing PTCA
Total occlusion
[surrogate]
PTCA-STENT
No
20
Data synthesized in the metaanalysis
No significant gene-gene
interaction was observed
Allele contrast OR=1.71 (0.8-3.6)
Domin model OR=0.89 (0.2-3.2)
Recess model OR=2.98 (1.1-8.1)
Gross, 2007,
Germany [48]
cohort
1 year
Hamon, 2003,
France [49]
cohort
2 years
Prisco, 2000,
Italy [50]
cohort
1 year
Ribichini,
2003, Italy
[51]
Guneri, 2005,
Turkey [52]
Okamura,1999
, Japan [53]
Okumura,
2002, Japan
[54]
Ferrari, 2002,
multicenter
(Europe) [55]
Koch, 2003,
Germany [56]
81 (70/11), Eur Whites, 59/2 (1.4), CAD
patients undergoing repeat PTCA for in-stent
restenotic lesions at FU angiography
1010 (813/197), Eur Whites, 64 (11),
symptomatic CAD patients treated with
successful PTCA-STENT
29 (nr), Eur Whites, 60 (46-75), MI patients
undergoing primary PTCA
Recurrent
Restenosis (1)
[surrogate]
Major adverse
cardiac event (6)
[clinical]
Endothelial
dysfunction (7)
[surrogate]
PTCA-STENT
No
31
Allele contrast OR=1.03 (0.5-2.0)
Domin model OR=0.51 (0.1-2.9)
Recess model OR=1.38 (0.5-3.9)
No association between ACE
genotype and clinical outcome
was observed
ACE DD genotype was
significantly (P=0.04) associated
with an increase of PAI-1activity
post PTCA [recess model OR=
6.52 (4.8-8.2)]. No significant
gene-gene interaction was
observed
PTCA-STENT
No
33
PTCA-STENT
Yes (AGT1R,
PAI-1)
34
No
35
Data synthesized in the metaanalysis
Cohort
6.3 (2.5)
months
cohort
9 months
(2.9)
cohort
6 months
271 (nr), Eur Whites, 61 (10), CAD patients
undergoing PTCA
Restenosis (3)
[surrogate]
Angioplasty
with ACEi
treatment
PTCA-STENT
+ ACEi
94 (59/35), Turks, 59.6 (9.9), CAD diabetic
patients undergoing PTCA for stable angina
pectoris
97 (84/13), East Asians, 60 (2), CAD patients
undergoing PTCA for stable angina pectoris
Restenosis (3)
[surrogate]
PTCA-STENT
+ ACEi
No
26
Data synthesized in the metaanalysis
Restenosis (3)
[surrogate]
No
29
Data synthesized in the metaanalysis
cohort
6 months
92 (73/19), East Asians, 64.3 (8.9), CAD
patients undergoing PTCA
Restenosis (3)
[surrogate]
No
22
Data synthesized in the metaanalysis
cohort
6 months
154 (119/35), Eur Whites, 61 (9.9), CAD
patients undergoing PTCA
Restenosis (1)
[surrogate]
PTCA-balloon
+ Imidapril 5
mg
PTCA-STENT
+ Quinapril
18mg
PTCA-STENT
+ ACEi
No
36
Data synthesized in the metaanalysis
cohort
1 year
612 (455/157), Eur Whites, 64.3 (9.5 ), CAD
patients with DD genotype undergoing
PTCA
Restenosis (3)
[surrogate]
Restenosis (8)
PTCA-STENT
+ ACEi
No
36
D homozygotes receiving ACEi
were not at a higher risk of
angiographic or clinical restenosis
[clinical]
than patients who were not
treated with ACEi (p=0.55)
Meurice, 2001,
France [57]
cohort
6 months
79 (67/12), Eur Whites, 58.9 (10.6), CAD
patients with DD genotype undergoing
PTCA
Restenosis (3)
[surrogate]
PTCA-STENT
+ Quinapril
20mg
No
32
D homozygotes receiving
Quinapril presented a trend
towards increased restenosis
compared to placebo
Data synthesized in the metaanalysis
Jorgensen,
2001,
Netherlands
[58]
Toyofyuku,
2002, Japan
[59]
cohort
6 months
369 (293/76), Eur Whites, 59 (43-73), CAD
patients undergoing PTCA for stable angina
Restenosis (3)
[surrogate]
PTCA-STENT
+ ACEi
No
40
RCT
6 months
204 (147/57), East Asians, 63.1 (1.0), CAD
patients undergoing PTCA randomized to
quinapril and placebo
Restenosis (3)
[surrogate]
PTCA-STENT
+ Quinapril
20mg
Yes (AGT)
30
No significant interaction
between ACE polymorphism and
quinapril treatment was observed
on the risk of restenosis. No
significant gene-gene interaction
was observed
Allele contrast OR=2.19 (0.9-4.8)
Domin model OR=4.78 (0.638.3)
Recess model OR=2.33 (0.8-6.7)
Allele contrast OR=0.90 (0.4-1.9)
Domin model OR=1.17 (0.2-5.7)
Recess model OR=0.71 (0.2-2.4)
Coronary
Atherectomy
Haberbosch,
1997,
Germany [60]
cohort
12-18
months
104 (91/13), Eur Whites, 60.2 (nr), CAD
patients undergoing DCA and PTCA
Restenosis (3)
[surrogate]
DCA-PTCASTENT
No
26
Canosi, 2004,
Italy [61]
Cohort
6.3 (1.5)
months
113 (103/10), Eur Whites, nr, CAD patients
undergoing DCA and PTCA
Restenosis (3)
[surrogate]
DCA-PTCASTENT
No
29
CABG
Dayi, 2005,
Turkey [62]
crosssectional
87 (71/16), Turks, 64.3 (7.3), CAD patients
treated with CABG before >5 years
undergoing angiography for symptoms
Venous graft
atherosclerosis (9)
[surrogate]
CABG
No
28
Ortlepp, 2001,
Germany [63]
cohort
88 (52)
months
101 (86/15), Eur Whites, 64.0 (8.1), CAD
patients after CABG presenting for
angiography due to angina pectoris
Venous graft
atherosclerosis
(10)
CABG
No
33
Allele contrast OR=2.41 (1.3-4.5)
Domin model OR=3.76 (1.212.2)
Recess model OR=3.75 (1.311.3)
The ACE I/D polymorphism was
not associated with by-pass
degeneration
[surrogate]
Volzke, 2002,
Germany [64]
cohort
2 years
247 (202/45), Eur Whites, 64.9 (nr), CAD
patients undergoing CABG
- total mortality
- cardiac mortality
or need for
recurrent
revascularization
[clinical]
CABG
No
35
Voors, 2004,
Netherlands
[65]
Cohort
12 months
82 (71/11), Eur Whites, 61.5 (1.3), CAD
undergoing CABG
endothelial
dysfunction (11)
[surrogate]
CABG
+quinapril
(40mg)
No
27
ACE I/D genotype is an
independent predictor of midterm
total mortality after CABG
[Mortality rate: II=0%,
ID=11.2%, DD=14.1%, p<0.05].
The ACE I/D genotype was also
an independent predictor of the
secondary end-point [cumulative
cardiac event incidence: II=5.8%,
ID=9.4%, DD=30.3%, p<0.005]
quinapril completely restored the
decreased vascular response in
DD-genotype patients to the same
level as II/ID genotype patients,
while no effect of quinapril was
demonstrated in the II/IDgenotype patients. Quinapril also
prevented the increase in plasma
ACE activity after CABG,
especially in DD homozygotes
Table 2. Invasive treatment study characteristics
* Outcome definition criteria: 1. Restenosis defined as >50% progression of the residual stenosis at FU angiography compared with the findings immediately after PTCA, 2.
Diagnostic criteria non-reported, 3. Restenosis defined as diameter stenosis >50% at FU angiography, 4. Endothelial dysfunction defined as coronary endothelium dependent
vasomotion after intracoronary infusions of acetylcholine, 5. Clinical restenosis defined as death from cardiac causes, MI attributable to target vessel and target vessel
revascularization, 6. Major adverse coronary event defined as death, MI, UA and coronary revascularisation, 7. Endothelial dysfunction defined as plasminogen activator inhibitor
activity post-PTCA, 8. Clinical restenosis defined as need for target vessel revascularization due to symptoms or signs of ischemia in the presence of angiographic restenosis over one
year after the intervention, 9. Venous graft atherosclerosis defined as total occlusion of venous graft, 10. Venous graft atherosclerosis defined by Gensini by-pass degeneration score,
11. Endothelial dysfunction defined as maximal vasoconstriction to angiotensin II.
Abbreviations: DCA: directional coronary atherectomy, FU: follow-up, UA: unstable angina, RCT: randomized controlled trial.