Patients treated with warfarin who undergo percutaneous coronary intervention (PCI) present a difficult therapeutic problem. Their baseline demographics, procedural characteristics, and 12-month outcomes are poorly defined. We conducted a retrospective analysis of all patients who underwent PCI at a major UK Cardiac Center from 2012 to 2013. Of the 2,675 patients who underwent PCI, 155 were on long-term warfarin treatment (5.8%). Patients on warfarin were older and more likely to have significant co-morbidity than those not on warfarin. The modified Mehran bleed score was higher in patients treated with warfarin versus those not treated (19.0 ± 5.8 vs 15.4 ± 8.0, p = 0.004). Baseline SYNTAX scores were higher in the patients treated with warfarin (18.5 ± 9.1 vs 12.4 ± 3.8, p = 0.0006) as were residual SYNTAX scores (8.3 ± 1.1 vs 3.8 ± 5.9, p = 0.001). Bare metal stents were more frequently used in warfarin-treated patients than those not treated (44.8% vs 26.3%, p <0.0001). Antiplatelet monotherapy was prescribed after PCI in 14.4% of patients treated with warfarin and 0.7% of non-warfarin (p <0.0001), whereas average dual anti-platelet therapy duration was also significantly shorter (4.3 vs 10.7 months, p <0.0001). At 1-year follow-up, target-vessel revascularization (6.5% vs 3.3%, p <0.05), stent thrombosis (5.0% vs 2.6%, p = 0.14), death (10.1% vs 4.6%, p <0.01), and target-vessel revascularization/stent thrombosis/death (21.6% vs 10.5%, p = 0.004) were all more common in the warfarin cohort. In conclusion, patients treated with warfarin who need PCI are a complex cohort, more likely to receive incomplete revascularization, less intense, and shorter durations of antiplatelet therapy, and have adverse 1-year outcomes. More trials of both current DES and newer DES technologies in warfarin-treated patients are needed.
Patients receiving chronic warfarin therapy who undergo percutaneous coronary intervention (PCI) are a small but difficult subgroup to manage. However, with a changing demographic profile in patients who underwent PCI (aging population) and a subsequent increased prevalence of atrial fibrillation and diabetes mellitus, interventional cardiologists are increasingly likely to face these difficult management decisions. Although data are accumulating with respect to the best strategy in terms of stent use and postprocedural antiplatelet management, the current evidence base has significant limitations. Data on optimal antiplatelet strategies in warfarin-treated patients after using current second-generation stents have largely been derived from a small number of studies, and given these data shortcomings, the current ESC guidelines only support their recommendations for PCI in patients on warfarin with a modest class IIa grading and with a level of evidence of C. Therefore, there remains a need for further trials to clarify the optimal strategy with currently available stents and drugs. Additionally, despite the increasing numbers of patients chronically treated with warfarin who need PCI, their characteristics and outcomes compared with those not treated with warfarin are poorly defined. Therefore, the aim of this study was to carefully define the baseline demographics, the PCI procedural characteristics, and the 1- and 12-month outcomes of patients treated chronically with warfarin who undergo PCI.
Methods
Our institution provides cardiac care to a population of nearly 1.5 million and performs in excess of 1,400 PCI a year. To generate sufficient numbers, all patients who underwent PCI in a 2-year period (2012 to 2013) were studied. The baseline demographics, procedural characteristics, and 12-month outcomes for patients treated with long-term warfarin who underwent PCI were compared with those not treated.
Warfarin treatment status data were taken from an internal hospital database. Patient demographics and procedural data were retrieved from the National British Cardiovascular Intervention Society Database Central Cardiac Audit (CCAD) database. The standard CCAD definitions of co-morbidity were used for the study purposes. Mortality was recorded from the Welsh Demographic Service database. Repeat target-vessel revascularization (TVR) data were derived from an internal angiographic database and the CCAD database. Stent thrombosis was defined as per the ARC definite criteria.
To assess baseline bleeding risk, we used the Mehran score. As with other studies, we modified this slightly by excluding periprocedural anticoagulant therapy. It is important to note that the Mehran bleed score does not include baseline use of warfarin. For SYNTAX score calculation, an on-line calculator was used ( http://ir-nwr.ru/calculators/syntaxscore.htm ). Scores were calculated by 4 experienced interventional cardiologists who were blinded as to the warfarin treatment status. To calculate baseline SYNTAX score, the pre-PCI angiograms were assessed and scored. To calculate residual SYNTAX score, the final post-PCI angiogram was scored to assess untreated disease. For patients who underwent multiple procedures on the same admission, the final postprocedure angiogram was used to calculate the residual score.
Continuous data were expressed as mean (SD), and comparison between groups was performed using Student’s t test. Categorical data are presented as frequencies and percentages and were compared using the chi-square statistics.
Results
Of the 2,675 patients who underwent PCI in 2012 and 2013, 155 were on long-term warfarin (5.8%). The main indications for warfarin therapy were atrial fibrillation (permanent 62.5% and paroxysmal 16.2%), thromboembolic disease (13.2%), LV thrombus (3.7%), and prosthetic heart valve (2.9%). The baseline demographics are described in Table 1 . Patients on warfarin were older (73.0 ± 11.3 vs 65.6 ± 11.8 years, p <0.0001), more likely to have a history of CABG (14.1% vs 5.8%, p <0.0001), MI (35.4% vs 28.7%, p <0.05), or severe LV dysfunction (15.0% vs 5.8%, p = 0.078), and more likely to have significant co-morbidity including hypertension (73.4% vs 63.4%, p <0.01), diabetes (21.1% vs 17.4%, p <0.05), chronic kidney disease (5.2% vs 3.2%, p <0.05), peripheral vascular disease (7.0% vs 2.6%, p <0.001), or history of stroke (5.1% vs 1.6%, p <0.001) than those not on warfarin. The main indications for chronic warfarin therapy were atrial fibrillation (62.1% sustained AF and 16.1% paroxysmal AF), thromboembolic disease (13.1%), left ventricular thrombus (3.6%), and mechanical heart valves (2.9%).
| Warfarin therapy | p value | ||
|---|---|---|---|
| Yes (n=155) | No (n=2520) | ||
| Age (years) | 73.0±11.3 | 65.6±11.8 | <0.0001 |
| Men | 75.9% | 74.2% | 0.18 |
| Body mass index | 28.5±5.4 | 28.6±5.5 | 0.36 |
| Hypertension | 73.4% | 64.1% | 0.011 |
| Diabetes mellitus | 21.1% | 17.4% | 0.049 |
| Peripheral vascular disease | 7.0% | 2.6% | 0.0002 |
| Cerebrovascular disease | 5.1% | 1.6% | 0.0003 |
| Chronic kidney disease | 5.2% | 3.2% | 0.047 |
| History of myocardial infarction | 35.4% | 28.7% | 0.033 |
| History of bypass grafting | 14.1% | 5.5% | <0.0001 |
| Previous PCI | 18.8% | 22.5% | 0.17 |
| Ejection fraction <30% | 15.0% | 5.8% | 0.078 |
| Q wave present | 12.3% | 8.4% | 0.030 |
| Acute coronary syndrome | 63.1% | 72.1% | 0.01 |
| Troponin +ve presentation | 52.3% | 60.1% | 0.029 |
| Ventilated pre-procedure | 0% | 1.8% | 0.047 |
| Shock on presentation | 3.2 | 4.6 | 0.15 |
| Angina class | 2.62±1.17 | 2.67±1.14 | 0.31 |
| NYHA class | 1.73±0.79 | 1.67±0.82 | 0.21 |
| Mehran bleed score | 19.0±5.8 | 15.4±8.0 | 0.004 |
The modified Mehran bleed score ( Table 2 ) was higher in patients treated with warfarin versus those not treated (19.0 ± 5.8 vs 15.4 ± 8.0, p = 0.004) with high or very high scores also more common (78.7% vs 43.8%, p <0.001; Figure 1 ). The individual components of the Mehran score are also detailed in Table 2 ; the main drivers of a high score in the warfarin-treated patients appeared to be age (73.0 ± 11.3 vs 65.6 ± 11.8 years, p <0.0001) and baseline anemia (12.9 ± 2.2 vs 13.6 ± 1.4 g/dl, p = 0.04).
| Warfarin therapy | p value | ||
|---|---|---|---|
| Yes (n=155) | No (n=2520) | ||
| Mehran bleed score | 19.0±5.8 | 15.4±8.0 | 0.004 |
| Female | 24.1% | 25.8% | 0.18 |
| Age (years) | 73.0±11.3 | 65.6±11.8 | <0.0001 |
| Haemoglobin (g/l) | 129±22 | 136±14 | 0.04 |
| WBC count (10 9 /l) | 8.9±2.8 | 9.9±3.2 | 0.02 |
| ST elevation myocardial infarction | 31.9% | 40.5% | 0.09 |
| Non-ST elevation myocardial infarction | 57.4 | 52.8 | 0.22 |
| Creatinine (mg/dl) | 1.07 | 1.01 | 0.20 |
Baseline SYNTAX scores were higher in the patients treated with warfarin (19.7 ± 11.4 vs 14.1 ± 8.5, p = 0.0002, Table 3 ). Additionally, significantly more patients treated with warfarin were classified as high (14.4% vs 4.7%, p <0.05) or intermediate (20.1% vs 7.1%, p <0.01) complexity than those not treated. During PCI, patients treated with warfarin ( Table 4 ) were more likely to undergo left main or graft intervention. Despite the higher SYNTAX scores and more complex PCI, the number of vessels and number of lesions treated were similar between cohorts. Again in contrast to the high baseline SYNTAX score, bare metal stents (BMS) were more frequently used in warfarin-treated patients than those not treated (44.8% vs 26.3%, p <0.0001). Although BMS use was higher in the warfarin cohort, mean maximum stent size was smaller (3.17 ± 0.97 vs 3.41 ± 1.45 mm, p = 0.025). Additionally, procedural success (operator defined) was lower in warfarin-treated patients (92.9% vs 95.0%, p <0.05), whereas an intraprocedural complication, such as major side-branch loss, coronary dissection, or slow flow (3.3% vs 2.5%, p <0.05) and TIMI 3 flow <3 (6.7% vs 3.2%, p = 0.008) were more common. Residual SYNTAX score was also significantly higher in patients treated with warfarin (7.7 ± 4.1 vs 4.5 ± 5.5, p = 0.001, Table 3 ). A residual SYNYTAX score of “0” was achieved in 38.8% of non-warfarin– versus 25.5% of warfarin-treated patients (p <0.05).
| Warfarin therapy | p value | ||
|---|---|---|---|
| Yes (n=155) | No (n=2520) | ||
| Baseline SYNTAX score | 19.7±11.4 | 14.1±8.5 | 0.0002 |
| High | 14.4% | 4.7% | 0.0002 |
| Intermediate | 20.1% | 7.1% | <0.01 |
| Low (%) | 65.5% | 88.2% | <0.05 |
| Residual SYNTAX score | 7.7±4.1 | 4.5±5.5 | 0.001 |
| Zero residual score | 25.5% | 38.8% | <0.05 |
| Warfarin therapy | p value | ||
|---|---|---|---|
| Yes (n=155) | No (n=2520) | ||
| Femoral access | 7.0% | 9.5% | 0.20 |
| Restenosis indication | 2.1% | 3.1% | 0.20 |
| Glycoprotein inhibitor used | 6.6% | 7.7% | 0.412 |
| Left main intervention | 4.6% | 3.6% | 0.038 |
| Proximal left anterior descending | 37.2% | 33.8% | 0.18 |
| Any left anterior descending | 56.8% | 49.9% | 0.049 |
| Left main or left anterior descending | 61.2% | 53.5% | 0.022 |
| Circumflex artery | 20.2% | 25.9% | 0.07 |
| Right artery | 31.4% | 37.9% | 0.06 |
| Circumflex or right artery | 51.6% | 63.8% | 0.002 |
| Any bypass graft intervention | 5.9% | 3.6% | 0.029 |
| Chronic total occlusion intervention | 4.5% | 7.6% | 0.12 |
| Number of vessels treated | 1.16±0.44 | 1.24±0.56 | 0.13 |
| Number of lesions treated | 1.49±0.81 | 1.55±0.81 | 0.22 |
| Drug-eluting stent used | 55.2% | 73.7% | <0.0001 |
| Mean number of stents used | 1.78±1.15 | 1.78±1.04 | 0.49 |
| Balloon only, no stents used | 13.3% | 6.9% | 0.001 |
| Largest balloon used (mm) | 3.17±0.97 | 3.41±1.45 | 0.025 |
| Longest stent used (mm) | 20.6±9.0 | 23.0±8.4 | 0.0003 |
| Procedural complication | 3.3% | 2.5% | 0.033 |
| Diagnostic device used | 22.9% | 17.9% | 0.047 |
| Arterial complication | 0.6% | 0.5% | 0.27 |
| Thrombus extraction | 14.6% | 18.7% | 0.13 |
| Distal protection used | 1.3% | 0.6% | 0.035 |
| Atherectomy device | 12.1% | 6.6% | 0.002 |
| Procedural success | 92.9% | 95.0% | 0.076 |
| TIMI flow <3 | 6.7% | 3.2% | 0.008 |
Antiplatelet monotherapy (>95% with clopidogrel only) was prescribed after PCI in 14.4% of patients treated with warfarin and 0.7% of non-warfarin (p <0.0001), whereas for those prescribed dual anti-platelet therapy (DAPT) average recommended duration was also significantly shorter (4.3 vs 10.7 months, p <0.0001; Table 4 ). Inhospital and 30-day MACE rates were not statistically different although numerically trended to show worse outcomes in the warfarin cohort ( Table 5 ). However at 1-year follow-up TVR, definite stent thrombosis, death, and a combined TVR/ST/death were all more common in the warfarin cohort. Among the patients who died, the mortality excess in those treated with warfarin was evenly distributed between cardiac death (5.0% for patients treated with warfarin vs 2.6% for non-warfarin) and noncardiac death (5.0% vs 1.9%). Interestingly non-TVR rates were similar between the 2 groups, indicating that patients treated with warfarin were left long term with partial revascularization.
