Ad hoc vs. Non-ad hoc Percutaneous Coronary Intervention Strategies in Patients With Stable Coronary Artery Disease

Toshiaki Toyota; Takeshi Morimoto; Hiroki Shiomi; Kenji Ando; Koh Ono; Satoshi Shizuta; Takao Kato; Naritatsu Saito; Yutaka Furukawa; Yoshihisa Nakagawa; Minoru Horie; Takeshi Kimura; on behalf of the CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators

doi:10.1253/circj.CJ-16-0987

Abstract

Background: Few studies have evaluated the prevalence and clinical outcomes of ad hoc percutaneous coronary intervention (PCI), performing diagnostic coronary angiography and PCI in the same session, in stable coronary artery disease (CAD) patients.

Methods and Results: From the CREDO-Kyoto PCI/CABG registry cohort-2, 6,943 patients were analyzed as having stable CAD and undergoing first PCI. Ad hoc PCI and non-ad hoc PCI were performed in 1,722 (24.8%) and 5,221 (75.1%) patients, respectively. The cumulative 5-year incidence and adjusted risk for all-cause death were not significantly different between the 2 groups (15% vs. 15%, P=0.53; hazard ratio: 1.15, 95% confidence interval: 0.98–1.35, P=0.08). Ad hoc PCI relative to non-ad hoc PCI was associated with neutral risk for myocardial infarction, any coronary revascularization, and bleeding, but was associated with a trend towards lower risk for stroke (hazard ratio: 0.78, 95% confidence interval: 0.60–1.02, P=0.06).

Conclusions: Ad hoc PCI in stable CAD patients was associated with at least comparable 5-year clinical outcomes as with non-ad hoc PCI. Considering patients’ preference and the cost-saving, the ad hoc PCI strategy might be a safe and attractive option for patients with stable CAD, although the prevalence of ad hoc PCI was low in the current study population.

The ad hoc percutaneous coronary intervention (PCI), that is, performing PCI immediately following diagnostic coronary angiography (CAG), is an attractive option, because it could meet patients’ preference by avoiding multiple invasive procedures and it is cost-saving if performed without major complications. Historically, the guideline recommendation for ad hoc PCI has gradually expanded with the improved safety of PCI procedures. The first American guidelines for coronary revascularization denied ad hoc balloon angioplasty.¹ However, subsequent guidelines suggested some patient subgroups as suitable for ad hoc PCI, in cases where the appropriateness of PCI is anticipated.² The 2011 American guidelines and the focused update in 2015 did not address ad hoc PCI, except for the recommendation in patients with acute coronary syndrome (ACS) and ongoing myocardial ischemia, which should be treated on an ad hoc PCI basis.³^,⁴ The Society for Cardiovascular Angiography and Interventions (SCAI) consensus statement for ad hoc PCI in 2013, and the 2014 European guidelines on myocardial ischemia stated the indications for ad hoc PCI in more detail; ad hoc PCI could be considered in patients with single-vessel disease, those with chronic kidney disease and diffuse atherosclerosis, and in patients with ST-segment elevation myocardial infarction (MI) or patients with ACS suitable for early invasive strategy, but ad hoc PCI could not be recommended for stable patients with chronic total occlusions and/or complex coronary lesion anatomy who might benefit more from coronary artery bypass grafting (CABG) than PCI.⁵^,⁶ In addition, both the recent guidelines and the SCAI consensus statements put emphasis on a multidisciplinary heart-team approach and the patient’s informed consent to decide the type of coronary revascularization procedure (PCI vs. CABG) and the timing of revascularization in patients with stable coronary artery disease (CAD).³^–⁶ Several previous observational studies demonstrated basically similar in-hospital clinical outcomes after ad hoc PCI as after non-ad hoc PCI.⁷^–¹⁰ However, there is limited evaluation of the prevalence and clinical outcomes of ad hoc PCI in patients with stable CAD, because all the previous studies included a large proportion of ACS patients.⁷^–¹¹ Evaluating the safety and efficacy of ad hoc PCI compared with non-ad hoc PCI is particularly relevant for stable CAD patients with complex coronary anatomy.

Therefore, we sought to evaluate the effects of the ad hoc PCI on clinical outcomes in such patients, using a large Japanese registry of patients who underwent their first coronary revascularization.

Methods

The CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) PCI/CABG registry cohort-2 is a physician-initiated non-company-sponsored multicenter registry that enrolled consecutive patients who underwent their first coronary revascularization between January 2005 and December 2007 at 26 tertiary hospitals in Japan (Appendix S1). The study design and patient enrollment of the registry were previously described in detail.¹²^,¹³ Among 15,939 patients enrolled in the registry, the current study population consisted of 6,943 patients who underwent their first PCI for stable CAD, after excluding those patients who refused study participation, who were treated by CABG, who had acute MI, unstable angina or underwent emergency PCI procedures, and who underwent diagnostic CAG in the referral hospital (Figure 1). In the present analysis, the long-term clinical outcomes after ad hoc PCI were compared with those after non-ad hoc PCI. Ad hoc PCI was defined as PCI performed in the same session as index diagnostic invasive CAG, while non-ad hoc PCI was defined as PCI performed in a separate session after diagnostic CAG.

Figure 1.

Study flow chart. CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; CREDO-Kyoto PCI/CABG registry, Coronary REvascularization Demonstrating Outcome Study in Kyoto percutaneous coronary intervention/coronary artery bypass graft surgery registry; PCI, percutaneous coronary intervention.

Written informed consent from the patients was waived because of the retrospective enrollment, although we excluded those patients who refused to participate in the study when contacted for follow-up. The research protocol, including waiver of informed consent, was approved by the local ethics committees in all 26 participating medical centers.

The primary outcome measure in the current analysis was all-cause death during 5-year follow-up. The secondary outcome measures included MI, stroke, any coronary revascularization, and bleeding during 5-year follow-up. We defined MI according to the definition in the Arterial Revascularization Therapy Study.¹⁴ Stroke was defined as ischemic or hemorrhagic stroke either occurring during the index hospitalization or requiring hospitalization with symptoms lasting >24 h. Any coronary revascularization was defined as either PCI or CABG for any reason. Scheduled staged PCI procedures performed during the index hospitalization or within 3 months of the initial procedure were not regarded as follow-up events, but were included in the index procedures. Bleeding was defined as moderate or severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) criteria.¹⁵

We also analyzed the 30-day incidence of death, MI, stroke, CABG, bleeding, and contrast-induced nephropathy to evaluate procedural complications. Contrast-induced nephropathy was defined as an increase in the peak serum creatinine concentration ≥0.5 mg/dL after PCI compared with the serum creatinine concentration before PCI according to previous studies.¹⁶^,¹⁷ The incidence of contrast-induced nephropathy was estimated in patients who had paired serum creatinine data before and after PCI during their index hospitalization.

Subgroup analyses were performed for the primary and secondary outcome measures based on age, sex, presence of multivessel disease or left main CAD, severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m² or hemodialysis), and heart failure, in an attempt to identify the subgroups of patients in whom ad hoc PCI carries higher risk as compared with non-ad hoc PCI.

The roles of the clinical research coordinators and clinical event committee are listed in Appendix S2 and Appendix S3, respectively.

Statistical Analysis

Continuous variables are expressed as mean and standard deviation, or median with interquartile range. Categorical variables are expressed as numbers and percentages. We compared continuous variables with Student’s t-test or the Wilcoxon rank-sum test on the basis of the distributions. We compared categorical variables with the χ² test as appropriate; otherwise, we used Fisher’s exact test.

Cumulative incidences of clinical events were estimated by the Kaplan-Meier method, and differences were assessed with the log-rank test. Multivariable Cox proportional-hazards models were used to evaluate the risk of the ad hoc PCI strategy relative to the non-ad hoc strategy for the primary and secondary outcome measures, which was expressed as hazard ratio (HR) and its 95% confidence interval (CI). Because of the small number of events for some endpoints, we selected 15 clinically relevant risk-adjusting variables listed in Table 1: age ≥75 years, male sex, diabetes insulin use, heart failure, multivessel disease or left main coronary artery, prior MI, prior stroke, peripheral arterial disease, estimated glomerular filtration rate <30 mL/min/1.73 m² or on dialysis, atrial fibrillation, malignancy, target of proximal left anterior descending artery, target of chronic total occlusion, target of bifurcation, and drug-eluting stent use, and the participating center was incorporated as the stratification variable.¹²^,¹³

Table 1. Clinical Characteristics: Ad hoc PCI vs. Non-ad hoc PCI

	Ad hoc PCI	Non-ad hoc PCI	P value
No. of patients	1,722	5,221
Characteristics
Age (years)	68.1±10.6	68.8±10.0	0.03
≥75 years*	511 (30)	1,633 (31)	0.21
Male*	1,238 (72)	3,725 (71)	0.66
Body mass index	23.8±3.6	23.9±3.5	0.32
<25 kg/m²	1,173 (68)	3,440 (66)	0.09
Hypertension	1,439 (84)	4,401 (84)	0.47
Diabetes	673 (39)	2,150 (41)	0.12
Insulin use*	142 (8.3)	537 (10)	0.01
Oral hypoglycemic agents use	431 (25)	1,315 (25)	0.90
Current smoking	437 (25)	1,349 (26)	0.70
Heart failure*	217 (13)	783 (15)	0.01
Multivessel disease or LMCA*	951 (55)	3,135 (60)	<0.001
Mitral regurgitation ≥3	56 (3.3)	272 (5.2)	<0.001
Left ventricular ejection fraction (%)	63±12	60±13	<0.001
≤40%	84/1,372 (6.1)	405/4,853 (8.4)	0.007
Prior myocardial infarction*	227 (13)	831 (16)	0.006
Prior stroke*	195 (11)	609 (12)	0.70
Peripheral arterial disease*	142 (8.3)	601 (12)	<0.001
eGFR <30 mL/min/1.73 m², not on dialysis	46 (2.7)	208 (4.0)	0.01
Dialysis	63 (3.7)	278 (5.3)	0.006
eGFR <30 mL/min/1.73 m², or on dialysis*	109 (6.3)	486 (9.3)	<0.001
Atrial fibrillation*	117 (6.8)	455 (8.7)	0.01
Anemia (hemoglobin <11 g/dL)	186 (11)	677 (13)	0.02
Platelet <100*10⁹/L	18 (1.1)	66 (1.3)	0.47
Triglyceride ≥150 mg/dL	516/1,574 (33)	1,633/4,752 (34)	0.25
LDL ≥140 mg/dL	332/1,409 (24)	996/4,345 (23)	0.62
HDL <40 mg/dL	383/1,465 (26)	1,194/4,521 (26)	0.84
Chronic obstructive pulmonary disease	59 (3.4)	202 (3.9)	0.40
Liver cirrhosis	38 (2.2)	147 (2.8)	0.17
Malignancy*	177 (10)	519 (9.9)	0.69
Medications
Aspirin	1,700 (99)	5,136 (98)	0.31
Thienopyridine	1,671 (97)	5,151 (99)	<0.001
Cilostazole	232 (13)	401 (7.7)	<0.001
Statins	920 (53)	2,556 (49)	0.001
β-blockers	418 (24)	1,313 (25)	0.47
ACEI/ARBs	826 (48)	2,664 (51)	0.03
Nitrates	577 (34)	2,059 (39)	<0.001
Calcium-channel blockers	858 (50)	2,746 (53)	0.046
Nicorandil	405 (24)	1,043 (20)	0.002
Warfarin	100 (5.8)	426 (8.2)	0.001
Proton pump inhibitors	420 (24)	931 (18)	<0.001
H2 blockers	316 (18)	1,164 (22)	<0.001
α-glucosidase inhibitors	159 (9.2)	495 (9.5)	0.76
Sulfonylureas	274 (16)	789 (15)	0.42
Biguanides	60 (3.5)	196 (3.8)	0.61
Pioglitazone	74 (4.3)	203 (3.9)	0.45
Angiographic characteristics
No. of diseased vessels			<0.001
1	771 (45)	2,086 (40)
2	588 (34)	1,707 (33)
3	292 (17)	1,231 (24)
LMCA disease	71 (4.1)	197 (3.8)
Lesion location
LAD	1,309 (76)	3,955 (76)	0.82
RCA	833 (48)	2,882 (55)	<0.001
LCX	802 (47)	2,735 (52)	<0.001
LMCA	71 (4.1)	197 (3.8)	0.51
Procedural characteristics
Index PCI procedures
No. of target lesions	1.20±0.47	1.25±0.54	<0.001
Target of proximal LAD	867 (50)	2,677 (51)	0.51
Target of unprotected LMCA	52 (3.0)	147 (2.8)	0.66
Target of chronic total obstruction	175 (10)	862 (17)	<0.001
Target of bifurcation	526 (31)	1,615 (31)	0.76
Side-branch stenting	54 (3.1)	241 (4.6)	0.008
Drug-eluting stent use	1,187 (69)	3,335 (64)	<0.001
No. of implanted stents	1.53±0.88	1.62±0.94	<0.001
Total stent length (mm)	33±22	35±23	0.02
Total stent length >28 mm	650/1,630 (40)	2,205/4,924 (45)	<0.001
Minimal stent diameter (mm)	2.98±0.44	2.88±0.43	<0.001
Minimal stent diameter <3.0 mm	591/1,620 (36)	2,277/4,887 (47)	<0.001
Radial approach	848 (49)	1,604 (31)	<0.001
Contrast media (mL)	190 (142–250)	155 (105–220)	<0.001
Fluoroscopy time (s)	1,776 (1,122–2,573)	1,622 (948–2,533)	0.15
IVUS use	989 (57)	2,255 (43)	<0.001
Antiplatelets before PCI
Aspirin	1,504 (87)	5,036 (96)	<0.001
Thienopyridine	1,322 (77)	4,962 (95)	<0.001
Cilostazole	115 (6.7)	296 (5.7)	0.12
Dual antiplatelet therapy	1,294 (75)	4,880 (93)	<0.001
Overall PCI procedure
No. of target lesions	1.48±0.75	1.48±0.76	0.81
Target of proximal LAD*	1,052 (61)	3,015 (58)	0.01
Target of unprotected LMCA	61 (3.5)	168 (3.2)	0.51
Target of chronic total occlusion*	205 (12)	926 (18)	<0.001
Target of bifurcation*	631 (37)	1,783 (34)	0.06
Side-brunch stenting	69 (4.0)	281 (5.4)	0.02
Drug-eluting stent*	1,242 (76)	3,409 (69)	<0.001
No. of implanted stents	1.92±1.23	1.93±1.27	0.82
Total stent length (mm)	42±31	41±29	0.17
Total stent length >28 mm	828/1,634 (51)	2,595/4,931 (53)	0.17
Minimal stent diameter (mm)	2.92±0.44	2.85±0.42	<0.001
Minimal stent diameter <3.0 mm	698/1,634 (43)	2,522/4,931 (51)	<0.001
No. of patient with staged PCI (%)	380 (22)	926 (18)	<0.001
No. of staged PCI	1.11±0.32	1.07±0.26	0.06

Continuous variables are shown as mean±standard deviation or median (interquartile range). The procedural details for the staged PCI procedures are shown in the Appendix. *15 potential independent variables selected in the multivariable analyses for all the outcome measures in the entire cohort and the subgroup analyses. ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin-receptor blocker; eGFR, estimated glomerular filtration rate; H2 blockers, histamine type 2 receptor blockers; HDL, high-density lipoprotein; IVUS, intravascular ultrasound; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LDL, low-density lipoprotein; LMCA, left main coronary artery; PCI, percutaneous coronary intervention; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction.

All statistical analyses were conducted using JMP 10.0 and SAS 9.4 (SAS Institute Inc., Cary, NC, USA). All the statistical analyses were 2-tailed and P<0.05 was considered statistically significant.

Results

Among the 6,943 study patients, only 1,722 (24.8%) underwent ad hoc PCI and 5,221 (75.2%) had non-ad hoc PCI. In the non-ad hoc group, PCI was performed a median of 7 (interquartile range: 4–15) days after diagnostic CAG. There was a marked variation in the prevalence of ad hoc PCI across the participating institutions (3–87%) (Figure 2).

Figure 2.

Prevalence of ad hoc PCI according to institution. PCI, percutaneous coronary intervention.

Regarding the baseline characteristics, the ad hoc PCI group had slightly, but significantly, lower prevalence of patients with advanced age, heart failure, multivessel disease or left main coronary artery, and renal dysfunction (Table 1). As for the index PCI procedure, the ad hoc PCI group as compared with the non-ad hoc PCI group had significantly lower prevalence of triple-vessel disease, and chronic total occlusion target (Table 1). The prevalence of left main CAD was not different between the 2 groups. The total amount of contrast media used in the index PCI procedure was greater in the ad hoc PCI group than in the non-ad hoc PCI group (Table 1). Details of the staged PCI procedures are listed in Table S1. For the overall PCI procedures, the ad hoc PCI group more often had patients with proximal left anterior descending coronary artery as the target than the non-ad hoc PCI group. The prevalence of unprotected left main coronary artery as the target was comparable between groups. The rate of dual antiplatelet therapy (DAPT) administration before PCI was significantly lower in the ad hoc PCI group compared with the non-ad hoc PCI group (75% vs. 93%) (Table 1). PCI success rates were high in both groups, although the complication rate during the index PCI was higher in the ad hoc PCI group relative to the non-ad hoc PCI group (9.4% vs. 7.3%, P=0.005), which was mainly driven by the higher rate of slow-flow during the procedure (4.0% vs. 2.6%, P=0.006). There were no differences in other procedural complications such as coronary perforation and dropped stent (Table S2).

The 30-day incidences of all-cause death, cardiac death and any coronary revascularization were slightly but significantly higher in the ad hoc PCI group compared with the non-ad hoc PCI group (Table 2). Details for the patients who had a cardiac death within 30 days are described separately (Table S3). There was no obvious relationship between ad hoc PCI strategy and death. The 30-day incidences of non-cardiac death, MI, definite/probable stent thrombosis, stroke, CABG, and bleeding were comparable between the 2 groups (Table 2).

Table 2. Crude and Adjusted Clinical Outcomes in the Entire Cohort and in the Subgroups: Ad hoc PCI vs. Non-ad hoc PCI

	No. of patients with event cumulative incidence (%)	P value	Crude HR (95% CI)	P value	Adjusted HR (95% CI)	P value
	Ad hoc vs. Non-ad hoc	P value	Crude HR (95% CI)	P value	Adjusted HR (95% CI)	P value
No. of patients	1,722 vs. 5,221
30-day outcomes
All-cause death	11 (0.6) vs. 14 (0.3)	0.03	2.39 (1.16–5.26)	0.04	–	–
Cardiac death	11 (0.6) vs. 11 (0.2)	0.006	NA
Non-cardiac death	0 (0.0) vs. 3 (0.006)	0.32	NA
Myocardial infarction	18 (1.1) vs. 46 (0.9)	0.54	1.19 (0.67–2.01)	0.54	–	–
Stent thrombosis	4 (0.2) vs. 17 (0.3)	0.54	0.71 (0.21–1.93)	0.53
Stroke	4 (0.2) vs. 21 (0.4)	0.31	0.58 (0.17–1.52)	0.29	–	–
Any coronary revascularization	39 (2.3) vs. 71 (1.4)	0.009	1.68 (1.13–2.47)	0.01	–	–
CABG	12 (0.7) vs. 27 (0.5)	0.39	1.36 (0.66–2.61)	0.39	–	–
Bleeding	35 (2.0) vs. 90 (1.7)	0.40	1.18 (0.79–1.73)	0.40	–	–
5-year outcomes
All-cause death	238 (15) vs. 754 (15)	0.53	0.96 (0.83–1.10)	0.53	1.15 (0.98–1.35)	0.08
Myocardial infarction	65 (4.1) vs. 214 (4.6)	0.91	0.98 (0.76–1.27)	0.91	1.10 (0.81–1.50)	0.53
Stroke	87 (5.8) vs. 325 (6.9)	0.03	0.78 (0.61–0.97)	0.02	0.78 (0.60–1.02)	0.07
Any coronary revascularization	537 (33) vs. 1,706 (35)	0.19	0.94 (0.85–1.03)	0.18	1.01 (0.90–1.13)	0.88
Bleeding	145 (9.4) vs. 545 (11)	0.02	0.81 (0.68–0.96)	0.01	0.94 (0.77–1.15)	0.56

CABG, coronary artery bypass graft surgery; HR, hazard ratio; NA, not available.

Contrast-induced nephropathy during the index hospitalization was evaluated in 4,784 patients (68.9%; ad hoc PCI group: 71.6%, non-ad hoc PCI group: 68.0%, P=0.005). The incidence of contrast-induced nephropathy was not significantly, but numerically lower in the ad hoc PCI group than in the non-ad hoc PCI group (3.0% vs. 4.0%, P=0.10), although the total amount of contrast media used in the index PCI procedure was greater in the ad hoc PCI group than in the non-ad hoc PCI group.

Median follow-up duration was 1,863 (interquartile range, 1,582–2,158) days. The cumulative 5-year incidences of all-cause death, MI, and any coronary revascularization were not significantly different between the ad hoc PCI group and non-ad hoc PCI group, while the cumulative incidences of stroke and bleeding were significantly lower in the ad hoc PCI group than in the non-ad hoc PCI group (Table 2). After adjusting for confounders, the risk of ad hoc PCI relative to non-ad hoc PCI was neutral for all-cause death, MI, any coronary revascularization, and bleeding, while the risk for stroke was numerically lower in the ad hoc PCI group than in the non-ad hoc PCI group (Table 2, Figure 3).

Figure 3.

Crude clinical outcomes: ad hoc PCI group vs. non-ad hoc PCI group. (A) all-cause death, (B) myocardial infarction, (C) stroke, (D) any coronary revascularization, and (E) bleeding. The crude cumulative incidences of all-cause death, myocardial infarction and any coronary revascularization were comparable between the 2 groups; however the cumulative incidences of stroke and bleeding were significantly lower in the ad hoc PCI group than in the non-ad hoc PCI group. PCI, percutaneous coronary intervention.

In the subgroup analyses, there was no statistically significant interaction between the subgroup factors and the effect of ad hoc PCI for any of the outcome measures evaluated (Figures 4,S1). Notably, the risk of the ad hoc PCI strategy relative to the non-ad hoc PCI strategy in patients with multivessel disease and/or left main CAD was also neutral for all the outcome measures evaluated.

Figure 4.

Crude and adjusted clinical outcome for all-cause death: ad hoc PCI group vs. non-ad hoc PCI group. The crude and adjusted P values of the Cox proportional hazard models were presented in the Table S2. CAD, coronary artery disease; CI, confidence interval; CKD, chronic kidney disease; HF, heart failure; HR, hazard ratio; LMCA, left main coronary artery; MVD, multivessel disease; N, number; PCI, percutaneous coronary intervention; SVD, single-vessel disease.

Discussion

The main findings of the current study were as follows: (1) the prevalence of ad hoc PCI in patients with stable CAD was relatively low in Japanese real clinical practice, with wide variations according to the institution; (2) the ad hoc PCI strategy was associated with similar short-term and long-term clinical outcomes as the non-ad hoc PCI strategy; and (3) there was no signal suggesting worse outcomes of the ad hoc PCI strategy relative to the non-ad hoc PCI strategy in the subgroup of patients with multivessel disease and/or left main CAD.

There has not been a randomized controlled trial comparing ad hoc PCI with non-ad hoc PCI in patients with stable CAD. Several previous observational studies demonstrated basically similar in-hospital complications after ad hoc PCI as those after non-ad hoc PCI.⁷^–¹⁰ Two relatively recent reports also provided long-term follow-up data with a conflicting result on long-term mortality; In the New York PCI Reporting System, ad hoc PCI was associated with a lower risk for 36-month mortality, while in the IRIS-DES registry, the risks for 18-month mortality and major adverse cardiovascular events were neutral between the ad hoc and non-ad hoc PCI groups.¹⁰^,¹¹ However, there is no previous study evaluating the prevalence and clinical outcomes of ad hoc PCI in patients with stable CAD, because all the previous studies included a large proportion of ACS patients. There is a reasonable rationale to perform ad hoc PCI in patients with ACS as an integral part of an early invasive strategy.¹⁸^,¹⁹ However, in patients with stable CAD, there remain several important issues, such as the appropriateness of PCI and adequate informed consent process.⁵^,⁶

In the present study, we restricted the study population to patients with stable CAD undergoing their first PCI. We included a large number of patients, and provided the details of the patient, lesion, and procedural characteristics as well as the long-term outcome data including not only mortality, but also MI, stroke, coronary revascularization and bleeding. Ad hoc PCI was less commonly performed than non-ad hoc PCI in the present study, although ad hoc PCI may be the dominant strategy outside Japan.⁹^–¹¹ One of the reasons for the relatively low prevalence of ad hoc PCI could be the inclusion criteria restricted to those patients undergoing their first PCI. Another reason might be the presence of a large proportion of patients with complex coronary anatomy in this registry. The prevalence of complex cases was significantly higher in the non-ad hoc PCI group than in the ad hoc PCI group. The non-ad hoc PCI strategy in patients with stable CAD allows careful discussion within the heart team and an appropriate process of informed consent after offering sufficient information to the patient. Furthermore, non-ad hoc PCI provides an economic incentive for the hospital management and predictable planning in the cardiac catheterization laboratory. It is likely that a large proportion of the participating centers adopted the non-ad hoc PCI strategy for these medical, economic and logistic reasons.

In the present study, the ad hoc PCI strategy was associated with long-term clinical outcomes at least comparable to those for the non-ad hoc PCI strategy, although 30-day mortality was marginally higher in the ad hoc PCI group compared with the non-ad hoc PCI group. The risk of ad hoc PCI relative to non-ad hoc PCI was neutral for all-cause death, MI, any coronary revascularization, and bleeding after adjusting for the clinical, angiographic, and procedural characteristics as well as the center, although the prevalence of complex patients was significantly higher in the non-ad hoc PCI group. The 5-year risk for stroke was numerically higher in the non-ad hoc PCI group compared with the ad hoc PCI group, suggesting the increased risk for stroke with multiple invasive procedures and intra-arterial catheter manipulation. Also, the incidence of contrast-induced nephropathy was numerically higher in the non-ad hoc PCI group than in the ad hoc PCI group, which might be explained by the higher prevalence of renal dysfunction in the non-ad hoc PCI group than in the ad hoc PCI group at baseline. Nevertheless, the high incidence rate of contrast-induced nephropathy might be consistent with the concept that repeated exposure to contrast material within a short time interval might predispose to the occurrence of contrast-induced nephropathy.²⁰^,²¹ Although performing diagnostic and interventional procedures separately reduces the total volume of contrast media exposure per each procedure, the risk of renal atheroembolic disease increases with multiple catheterizations. Therefore, a single, invasive ad hoc PCI approach may be considered for CKD patients with diffuse atherosclerosis, but only if the amount of contrast media can be maintained within 4 mL/kg. Furthermore, there was no signal suggesting worse outcomes of the ad hoc PCI strategy relative to the non-ad hoc PCI strategy in the subgroups of patients with multivessel disease and/or left main CAD. Therefore, the safety and efficacy of the ad hoc PCI procedure itself seemed to be validated in a wide range of patients with stable CAD. Regarding antiplatelet therapy in the ad hoc PCI group, the majority of patients received DAPT before diagnostic CAG. It is very likely that DAPT was also administered to patients in whom ad hoc PCI was scheduled, but was actually aborted, indicating that these patients were exposed to increased risk of bleeding complications at the time of diagnostic CAG. In the ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation MI) trial, pretreatment with prasugrel was not associated with a decrease in ischemic events, but was associated with an increase in bleeding complications.²² Therefore, newer ADP-receptor antagonists with their more rapid onset of action might enable us to omit unnecessary DAPT before the possible ad hoc PCI and we can safely start DAPT after the decision of PCI. The ad hoc PCI strategy is an attractive option meeting patients’ preference. By performing ad hoc PCI, we can avoid multiple invasive procedures, complications of diagnostic CAG and deterioration of clinical status while waiting for non-ad hoc PCI. Furthermore, at least theoretically, ad hoc PCI is cost-saving for both the patients and society.²³ Therefore, we have good reasons to promote ad hoc PCI in patients with stable CAD.

However, there obviously are negative aspects of the ad hoc PCI strategy, including concerns about an increase in inappropriate PCI procedures and the lack of adequate informed consent. There are 2 extremes of inappropriate PCI: physiologically non-significant lesions, and patients who would benefit more from CABG. We may not be so much concerned about an increase in inappropriate procedures by performing ad hoc PCI, if the presence of functional myocardial ischemia is adequately evaluated before diagnostic CAG. However, non-invasive functional tests for myocardial ischemia might not be performed in many patients with stable CAD undergoing planned ad hoc PCI or non-ad hoc PCI.²⁴ It could not be justified for the interventional cardiologists to rush into performing PCI without documentation of myocardial ischemia. Fractional flow reserve (FFR) measurement by intracoronary pressure wire is particularly pertinent to avoiding inappropriate PCI for a functionally non-significant lesion and to help choosing the appropriate target lesions in patients undergoing a planned ad hoc PCI.²⁵^,²⁶ However, invasive FFR measurement may increase the risk of complications and medical costs, particularly when the FFR result is negative. We should balance the benefits and potential risks of invasive FFR measurement. Regarding the other extreme of inappropriate PCI, there are several known subgroups of patients who would benefit more from CABG: diabetic patients with multivessel disease, and patients with triple-vessel disease and/or left main CAD who have high SYNTAX scores.²⁷^,²⁸ For these subgroups, there needs to be careful discussion by the heart team on the selection between PCI and CABG.³^,⁶ However, when we choose non-ad hoc PCI after heart-team discussion, the patient would have the inconvenience of a prolonged hospital stay, as well as the risk of deterioration of clinical status while waiting for non-ad hoc PCI, and complications from repeated invasive procedures. It would be ideal if we could have the heart-team discussion before or at the time of diagnostic CAG. Recently, coronary CT angiography has been increasingly and more widely used in real clinical practice, particularly in Japan.²⁹ Coronary CT angiography as the initial diagnostic test would provide detailed information on coronary anatomy sufficient for heart-team discussion. Furthermore, the recent development of CT-based FFR measurement would enhance our diagnostic ability for the extent of functionally significant CAD.³⁰ Regarding the lack of adequate informed consent, it is true that we can only provide patients and their families with general information on the risks and benefits of PCI, if we do not have coronary anatomic information. Coronary CT angiography would also help us to anticipate the details of the actual PCI procedure, to perform a heart-team assessment for the treatment strategy before the CAG, and to obtain adequate informed consent from the patient and family members based on the coronary anatomic information specific for the particular patient.³¹ Therefore, the use of coronary CT angiography as the initial diagnostic test, timely heart-team approach in severe CAD, and introduction of FFR-guided PCI might be the sine qua non for the appropriate implementation of the ad hoc PCI strategy. In addition, the operators performing ad hoc PCI should not only be experienced, but also know the details of the patient’s medical history. The last issue regarding the negative aspect of ad hoc PCI is that there is a concern about an increase in intraprocedural complications and short-term deaths. In the current analysis, the main component of the intraprocedural complications was limited to a higher incidence of slow-flow in the ad hoc PCI group than in the non-ad hoc PCI group. Also, the subgroup analysis especially for the extent of CAD showed no significant interaction between the subgroup factors and the risk of ad hoc PCI relative to non-ad hoc PCI. We need more data regarding the subgroups of patients who would benefit or be harmed more by ad hoc PCI. However appropriate medications before the procedure and detailed evaluation for the target lesions not only by angiographic lesion assessment, but also by intravascular imaging techniques might be beneficial for safe ad hoc PCI. With appropriate preparation for ad hoc PCI, the ideal candidates would be those patients who obviously do not have coronary anatomy more suitable for CABG.

Study Limitations

First, the observational study design precluded any definitive conclusion because of unmeasured confounders, and selection bias regarding the decision making for ad hoc PCI, although we conducted extensive statistical adjustment for measured confounders. We need a prospective randomized controlled study evaluating the safety and efficacy of ad hoc PC relative to non-ad hoc PCI, particularly in patients with complex clinical and/or angiographic characteristics. Second, there might be some concerns about the higher 30-day rate of cardiac death in the ad hoc PCI group. However, there was no obvious relationship between the ad hoc PCI strategy and death. Some of the patients who died within 30 days of ad hoc PCI had a serious clinical status before PCI, even if the procedure was not regarded as “emergency” (Table S3). Furthermore, the present study does not have sufficient statistical power to evaluate the 30-day mortality rate. Third, we did not evaluate the incidence of complications after diagnostic CAG in the non-ad hoc PCI group, or the occurrence of ACS events while waiting for scheduled non-ad hoc PCI procedures. Fourth, we do not know what proportion of the current study population underwent appropriate PCI based on functional assessment, because we did not collect data on non-invasive functional studies or FFR measurement. Fifth, we also did not have data on the number of patients who were referred for CABG after diagnostic CAG. Sixth, we did not conduct a cost analysis. Seventh, we did not collect data on complete coronary revascularization, although the number of target lesions was similar between the ad hoc and non-ad hoc PCI groups. Eighth, CT angiography might be beneficial for patients who are scheduled for ad hoc PCI. However, we should recognize that the use of CT angiography is associated with repeated contrast exposure and increased costs. Finally, the prevalence of ad hoc PCI in contemporary clinical practice might be different from that in the present study.

Conclusions

Ad hoc PCI in patients with stable CAD were associated with at least comparable 5-year clinical outcomes as compared with non-ad hoc PCI. Considering patients’ preference and the cost-saving, the ad hoc PCI strategy might be a safe and attractive option for patients with stable CAD, although the prevalence of ad hoc PCI was low in the current study population.

Acknowledgments

We appreciate the support and collaboration of the co-investigators participating in the CREDO-Kyoto PCI/CABG registry cohort-2. We are indebted to the outstanding effort of the clinical research coordinators for data collection.

Conflict of Interest Statement

Takeshi Morimoto discloses Education Consultant for Boston Scientific Corporation. The other authors have nothing to disclose concerning the discussed issue.

Funding

This study was funded by the Pharmaceuticals and Medical Devices Agency in Japan.

Supplementary Files

Supplementary File 1

Figure S1. Crude and adjusted clinical outcomes in the entire cohort and in the subgroups: Ad hoc PCI group vs. Non-ad hoc PCI group.

Table S1. Characteristics of the staged PCI procedures

Table S2. Characteristics of intraprocedural complications and bail-out procedures: Ad hoc PCI vs. Non-ad hoc PCI

Table S3. Characteristics of the patients with cardiac death within 30 days

Appendix S1. Participating Centers and Investigators for the CREDO-Kyoto PCI/CABG Registry Cohort-2

Appendix S2. List of Clinical Research Coordinators

Appendix S3. List of Clinical Event Committee Members

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-16-0987

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