|Year : 2022 | Volume
| Issue : 1 | Page : 30-37
Role of palliative percutaneous coronary intervention in severely symptomatic complex coronary artery disease patients who could not undergo coronary artery bypass surgery
Mukesh Tiwari1, Ashish Jha2, Bhuwan Chandra Tiwari2, Sudarshan K Vijay2, Naveen Jamwal2, Amresh Kumar Singh2
1 Department of Cardiology, MLNMC, Prayagraj, Uttar Pradesh, India
2 Department of Cardiology, Dr. RMLIMS, Lucknow, Uttar Pradesh, India
|Date of Submission||27-Jan-2022|
|Date of Decision||08-Feb-2022|
|Date of Acceptance||09-Feb-2022|
|Date of Web Publication||13-Apr-2022|
Dr. Bhuwan Chandra Tiwari
Department of Cardiology, Dr. RMLIMS, Vibhuti Khand, Gomti Nagar, Lucknow - 226 010, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Context: Patients with symptomatic complex coronary artery disease (CAD) who could not undergo bypass surgery for any reason often continue to have symptoms and impaired quality of life (QoL) on optimal medical therapy (OMT)
Aims: This study aimed to evaluate the role of palliative percutaneous coronary intervention (PCI) in these patients as compared to OMT alone.
Settings and Design: This was a prospective, questionnaire-based, case–control, single-center study.
Subjects and Methods: Patients in the case arm underwent palliative PCI of at least 1 target vessel and the control arm remained on OMT. The primary endpoint was a comparison of Seattle Angina Questionnaire (SAQ)-angina frequency (AF) and QoL scores at baseline, 3 months, and 6 months. Secondary outcomes were the difference in frequency of cardiovascular death, stroke, nonfatal myocardial infarction, and major bleeding episodes between 2 arms during the same period.
Results: The study recruited 200 patients (100 in each arm). Baseline characteristics were well matched. Presenting diagnosis was stable CAD in 11% and ACS in 89%. SAQ AF and QoL scores were similar in both arms at baseline, but a significant improvement in both parameters was seen at 3 and 6 months in palliative PCI arm. Predecided cutoffs for significant improvement in SAQ-AF and SAQ-QoL were achieved in palliative PCI arm. No significant difference was seen for secondary outcome measures between the two groups.
Conclusions: Palliative PCI provided a significant benefit in terms of improvement in SAQ-AF and SAQ-QoL scores, over short term (6 months), as compared to OMT alone in patients with severely symptomatic complex CAD, who could not undergo CABG.
Keywords: Complex CAD, Palliative PCI, CABG, palliative PCI vs OMT in complex CAD, SAQ: Seattle Angina Questionnaire
|How to cite this article:|
Tiwari M, Jha A, Tiwari BC, Vijay SK, Jamwal N, Singh AK. Role of palliative percutaneous coronary intervention in severely symptomatic complex coronary artery disease patients who could not undergo coronary artery bypass surgery. Heart India 2022;10:30-7
|How to cite this URL:|
Tiwari M, Jha A, Tiwari BC, Vijay SK, Jamwal N, Singh AK. Role of palliative percutaneous coronary intervention in severely symptomatic complex coronary artery disease patients who could not undergo coronary artery bypass surgery. Heart India [serial online] 2022 [cited 2022 May 16];10:30-7. Available from: https://www.heartindia.net/text.asp?2022/10/1/30/343070
| Introduction|| |
Coronary artery disease (CAD) is one of the most common causes of death and disability all over the world. Unlike developed countries, India is facing an ongoing epidemic of CAD. Indian patients with CAD tend to have more severe and complex CAD.
Several large randomized controlled trials (RCTs) have shown that coronary revascularization with Coronary Artery Bypass Graft (CABG) surgery has an edge over percutaneous coronary intervention (PCI) for management of patients with complex CAD (e.g., left main coronary artery disease or multivessel CAD with high SYNTAX score >32, LV dysfunction, and diabetic patients).,,,,,,,
Despite robust data, CABG is still underutilized, particularly in developing countries. High cost, prolonged hospital stays, and long waiting queues are practical concerns with CABG. A limited number of cardiac surgeons often result in a long waiting period for eligible patients, many of whom suffer from repeat ACS, heart failure and sudden death, awaiting surgery. These patients often have severe symptoms, limiting their quality of life (QoL). Palliative PCI may help in reducing symptoms in this subset. However, prospective studies evaluating whether palliative PCI done in these scenarios has any advantage over optimal medical therapy (OMT) alone are lacking. The present study was aimed to answer this question.
| Subjects and Methods|| |
The objective of the present study was to evaluate the outcome of palliative PCI in patients with complex CAD having significant anginal symptoms who were primarily a candidate for CABG but could not undergo it for any reason.
The primary outcome measure of the study was symptomatic relief after PCI based on the Seattle Angina Questionnaire-angina frequency (SAQ-AF) and SAQ-QoL scales., Secondary outcome measures were the difference in frequency of cardiovascular death, stroke, nonfatal myocardial infarction (MI), and major bleeding episodes between the case and control arms at baseline, 3 months, and 6 months of follow-up.
The present study was a prospective, questionnaire based, case–control study done at a tertiary care, teaching hospital in North India. The study protocol was approved by the institutional ethics committee. Written informed consent was obtained from all the participants before enrollment in the study. Recruitment for the study was done over 1 year with a minimum follow-up of 6 months.
Inclusion and exclusion criteria
Patients with complex CAD (defined as multivessel CAD or diffuse CAD, where it will not be possible to achieve complete revascularization with PCI or doing so will be at the cost of implanting multiple stents); who were advised for CABG as the first choice for their coronary revascularization but refused due to any reason; who are older than 18 years, and who have no contraindication to dual antiplatelet therapy were eligible to participate in the study, provided they had limiting angina (NYHA III/IV) and had at least one significant coronary artery stenosis amenable to PCI.
The study excluded patients who underwent CABG, had mild symptoms (NYHA Class I or II), had no coronary lesion amenable to PCI, and patients younger than 18 years.
Sample size calculation: Sample size for the study was calculated by the formula for the finite population. Assuming population size of 5000 meaning thereby the number of all angiographies done at our center during entire study duration, population proportion about 10% of all patients showing features of complex CAD at our center, a margin of error 5%, and confidence level of 95%, the sample size must be >135. Statistical analysis was performed using SPSS 21.0. Continuous data were presented as mean ± standard deviation. Qualitative data were presented as frequencies. Comparisons between groups were performed using Chi-square statistics and Fisher's exact test for categorical variables and paired and unpaired t-tests for continuous variables, or factorial analysis of variance. A significant difference was defined as a P ≤ 0.05.
Over the study duration of 1 year, a total of 200 patients were recruited in the study, of which 100 patients undergoing palliative PCI were assigned to the case group and the remaining 100 on OMT assigned to the control group.
Detailed history, clinical evaluation, routine laboratory investigations, ECG, and two-dimensional echocardiography were done in all patients during the index hospitalization. The SAQ-AF and SAQ-QoL scales were used to assess the primary outcome.,
The questionnaire was given to the participants at baseline, 3rd month, and 6th month. The questionnaire was translated into patients' native language. These scales range from 0 to 100, with higher scores indicating fewer symptoms and better QoL. An increase in the SAQ-AF score of 20 or more points or an increase in the SAQ-QoL score of 16 or more points were considered a clinically significant improvement. Poor symptomatic status was defined as SAQ-AF and SAQ-QoL scores <50 and/or NYHA Class III or IV symptoms.
For secondary outcomes, cardiac death, stroke, nonfatal MI, and major bleeding episode were measured. Cardiac death included sudden cardiac death, death due to acute MI, heart failure or cardiogenic shock. Nonfatal MI included both postprocedure MI and spontaneous MI. Standard definitions of spontaneous MI, periprocedural MI, and stroke were taken as per the ACC/AHA guidelines. Major bleeding was defined according to the TIMI bleeding classification. Adverse events were assessed during the hospitalization, at 3 and 6 months.
The decision regarding PCI and extent of revascularization was solely at the discretion of the treating operator and patient's preferences. Eligible patients underwent PCI for at least one significant stenosis. All the patients in the case group were put on dual antiplatelet agents and guideline-directed OMT after PCI, whereas the patients in the control group received OMT with the intention of maximum reduction in anginal symptom burden and improvement in QoL.
| Results|| |
Baseline characteristics of the patients are shown in [Table 1]. The mean age of the patients was 62.84 ± 8.97 years and 94% of patients were 50 years or older. Majority were males (86%). No significant difference was seen between case and control arms in terms of risk factors for CAD, comorbid conditions such as COAD, CKD, thyroid disorders, and past history of ASCVD such as ACS or stroke. The baseline biochemical tests were also similar in the two arms [Table 1].
Most of the patients were on aspirin, statins, and beta-blockers at baseline [Table 2]. No significant difference was observed between palliative PCI arm (case) and OMT alone arm (control) in terms of their medications at baseline.
CAD presentation was with ST segment elevation MI (STEMI) and non-ST segment elevation MI (NSTEMI) in 63% of patients in both arms and with stable CAD in 11% of patients [Table 3]. No significant difference was seen in terms of the presentation of CAD between the two groups. Most of the patients had triple-vessel CAD (96%). Left main CAD was observed in 15% of patients, chronic total occlusion in 25%, bifurcation lesion in 8%, and ostial lesions in 23.5% of patients [Table 3]. There was no significant difference between the two arms in terms of various types of coronary lesions and SYNTAX score. Majority of patients underwent multivessel PCI in palliative PCI arm with a mean number of stents implanted per patient of 3.8 ± 0.4 [Table 3].
|Table 3: Findings on angiography and percutaneous coronary intervention parameters|
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For the primary endpoint of AF and QoL, as measured by SAQ score, there was no difference between the two groups at baseline [Table 4]. A significant improvement was seen in SAQ (AF) and SAQ (QoL) score (higher value) at 3 and 6 months in palliative PCI arm, whereas these values worsened a little in the control arm at 3 and 6 months as compared to their baseline values [Table 4] and [Figure 1]. The improvement in SAQ (AF and QoL) parameters was similar across the spectrum of STEMI, NSTEMI, chronic stable angina (CSA), and UA [Table 5].
|Figure1: SAQ (AF) and SAQ (QoL) scores at baseline, 3 months and 6 months in case and control arms control arms. SAQ: Seattle Angina Questionnaire, AF: Angina frequency, QoL: Quality of life, 0: baseline value, 3: 3-month follow-up, 6: 6-month follow-up|
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|Table 4: Seattle Angina Questionnaire scores in case and control arms at baseline, 3 months, and 6 months|
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|Table 5: Seattle Angina Questionnaire (angina frequency) and Seattle Angina Questionnaire (quality of life) scores at baseline, 3 months, and 6 months in case and control arms in subjects presenting with ST segment elevation myocardial infarction, non-ST segment elevation myocardial infarction, chronic stable angina, and unstable angina|
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The secondary endpoints of cardiac death, nonfatal MI, CVA, and major bleed were numerically a little higher in palliative PCI arm as compared to OMT arm, but the difference was not statistically significant [Table 6]. The predecided cutoff of significant improvement in SAQ (AF) by 20 points and SAQ (QoL) by 16 points at 6 months when compared to baseline was seen in more than 80% of patients in palliative PCI arm. This improvement was consistently seen across the spectrum of presentation of CAD [Figure 2].
|Figure 2: Improvement on SAQ-AF and SAQ-QoL in PCI arm in different diagnostic groups. SAQ: Seattle Angina Questionnaire, AF: Angina frequency, QoL: Quality of life, 0: Baseline value, 3: 3-month follow-up, 6: 6-month follow-up, STEMI: ST segment elevation MI, NSTEMI: Non-ST segment elevation MI, USA: Unstable angina, CSA: Chronic stable angina|
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| Discussion|| |
Complex CAD is often associated with high symptom burden and a poorer outcome. Although symptom burden affecting QoL is the primary concern for which the patients seek medical attention, symptomatic improvement as a primary outcome has rarely been evaluated in studies conducted so far.
The present study included patients across the spectrum of CAD (ACS and stable CAD). Patients with complex CAD, who were eligible for CABG but did not undergo it, for any reason were studied. Among them, patients undergoing palliative PCI were placed in case group and the remaining on OMT served as controls. All the patients in intervention arm underwent PCI for at least one significant PCI amenable lesion. However, majority of the patients underwent multivessel PCI.
Symptomatic improvement was the primary outcome of the present study. It was assessed as improvement in SAQ scores, particularly SAQ-AF and SAQ-QoL scores. A statistically significant improvement in SAQ-AF and SAQ-QoL scores was seen in palliative PCI group as compared to the control group at 3 months and 6 months (P < 0.001). However, in control group, no improvement or even slight decline in the SAQ-AF score was noted.
Cardiovascular death, nonfatal MI, stroke, and major bleeding were taken as secondary outcomes in the present study. Although individual secondary outcomes were numerically greater in PCI group, no statistically significant difference in secondary outcomes was observed between case and control groups.
RITA-2 study compared the long-term outcomes of PCI versus OMT alone in patients with angina pectoris. The prevalence of angina decreased in both groups during the first 5 years of follow-up. However, this symptomatic improvement was much more rapid in the PTCA arm. Although at 5 year, the treatment difference was smaller, 6.4% in favor of PTCA, still, it was statistically significant (95% confidence interval, 1.5%-11.3%, P = 0.011). The results of the present study showed a similar trend as observed in RITA-2 study. However, the duration of follow-up in our study is only 6 months, and hence, long-term outcomes cannot be evaluated in the present study. Moreover, unlike RITA-2, only 11% of patients in the present study had stable CAD.
COURAGE trial compared OMT alone or in combination with PCI as an initial management strategy in patients with stable CAD. The addition of PCI to OMT showed a reduction in the prevalence of angina. However, it did not reduce long-term outcomes of death, nonfatal MI, and hospitalization for ACS during follow-up of 2.5–7.0 years. The present study also showed that palliative PCI resulted in a significant reduction in angina burden as compared to OMT alone; however, it included both stable CAD and ACS, whereas the COURAGE trial included stable CAD patients only. Inclusion of angiographic criteria and SAQ, which is a highly sensitive and specific questionnaire for evaluation of angina, makes our study somewhat different from this landmark trial.
The China PEACE prospective study was aimed to describe the characteristics and preprocedural angina-specific health status of patients without AMI who underwent PCI in China. It was a cohort study conducted for a duration of 1 year. The study included subjects with CSA and UA. Patients with acute MI were excluded. Among these patients, 38.9% had clinically improved QoL (change in SAQ QoL score ≥10 points) at 1 year, while 61.1% did not report clinically improved QoL. Unlike this study, the present study also included AMI patients. The symptomatic improvement noted at 6 months post PCI in our study was more heartening. However, these findings may be confounded by higher symptom burden at baseline in the present study population (only Class III and Class IV patients were recruited).
Only a few studies have evaluated improvement in AF and in QoL indices after PCI or CABG or in patients with angina on OMT, SYNTAX trial evaluated improvement in AF and QoL. The SAQ-AF score increased to a greater extent with CABG than with PCI at both 6 and 12 months (P = 0.04 and P = 0.03, respectively), but the differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were angina free was similar in both groups at 1 and 6 months and was higher in the CABG arm than in the PCI arm at 12 months (76.3% vs. 71.6%, P = 0.05). In contrast to the SYNTAX study, the present study evaluated SAQ scores in patients in whom CABG was indicated but could not be done due to any reason. The improvement in SAQ subscales of AF and QoL was significantly higher in PCI group as compared to that in OMT group, throughout the follow-up of 6 months. Unlike SYNTAX trial, the present study did not compare PCI with CABG in complex CAD patients.
Recently, the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial was published in NEJM. The ISCHEMIA trial failed to show any benefit of routine invasive therapy over OMT in reference to reduction in major adverse ischemic events among stable CAD patients with moderate-to-severe ischemia. One-third of subjects reported no angina symptoms at baseline. There was a minor improvement in symptom benefit at 3 months, especially among those with more frequent angina, which lasted for at least up to 12 and 36 months. Contrary to the results ISCHEMIA trial, the present study found more robust improvement in SAQ scores. Symptom burden at baseline was significantly greater in the present study as compared to ISCHEMIA trial. Even in the ISCHEMIA trial, those who had more severe symptoms, to begin with, tended to have a greater symptomatic benefit, which may be the reason for the observed benefits in the present study.
Ideally, all cases of complex CADs should be discussed in a heart team meeting, and the best treatment option should be provided to the patient as per the consensus of the team. In the present study, all the patients were referred to CTVS surgeon and only those who were unwilling for CABG even after CTVS surgeon's opinion were recruited in the study.
There are several limitations of the present study. It is a nonrandomized study. The duration of follow-up in the present study is only 6 months, and hence, long-term outcomes cannot be ascertained. The present study only recruited patients who were severely symptomatic at baseline, thus the results may not apply to mildly symptomatic complex CAD patients. Head-to-head comparison of CABG versus PCI was not done, so the present study is not meant to compare CABG with palliative PCI. Majority of recruited patients were males (~86%), thus there is a gender bias and results may not be applicable to female patients.
| Conclusions|| |
As suggested by various RCTs and guidelines, patients with symptomatic and complex CAD should undergo CABG as the first choice. However, the present study showed that in patients with severely symptomatic complex CAD who could not undergo CABG for any reason and having at least 1 coronary lesion amenable to PCI, palliative PCI provided a greater symptom relief and improvement in QoL as compared to OMT alone. As the number of such patients is increasing worldwide, palliative PCI is likely to be required in a large number of patients. Hence, further RCTs with a longer follow-up duration are required to have high-quality evidence for the utility of palliative PCI.
All procedures followed were in accordance with the ethical standards of institutional ethics committee and with the Helsinki Declaration of 1964 and later versions. Written informed consent was obtained from all patients participating in the study.
All the authors have contributed significantly in preparation of the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]