Abstract
OBJECTIVES
Despite guideline recommendations, previous reports, coming mainly from outside Europe, showed low rates of prescriptions for dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI) undergoing surgical revascularization. The present study assesses this issue in the era of potent P2Y12 inhibitors in Switzerland.
METHODS
All patients with a diagnosis of AMI included in the Acute Myocardial Infarction in Switzerland Plus Registry from January 2014 to December 2019 were screened; 9050 patients undergoing either percutaneous (8727, 96.5%) or surgical (323, 3.5%) revascularization were included in the analysis.
RESULTS
Surgically treated patients were significantly less likely to receive DAPT at discharge (56.3% vs 96.7%; P < 0.001). Even when discharged with a prescription for DAPT, those patients were significantly less likely to receive a regimen containing a new P2Y12 inhibitor (67/182 [36.8%] vs 6945/8440 [83.2%]; P < 0.001). At multivariate analysis, surgical revascularization was independently associated with a lower likelihood of receiving a prescription for DAPT at discharge (odds ratio 0.03, 95% confidence interval 0.02–0.06).
CONCLUSIONS
DAPT prescriptions for patients with AMI undergoing surgical revascularization are not in line with current guideline recommendations. Efforts are necessary to clarify the role of DAPT for secondary prevention in these patients and increase the confidence of treating physicians in guideline recommendations.
Clinical trial registration
Acute Myocardial Infarction in Switzerland Plus Registry; registration number at ClinicalTrials.gov: NCT01305785.
Keywords: Acute myocardial infarction, Coronary artery bypass graft, Dual antiplatelet therapy, Clopidogrel, Ticagrelor, Prasugrel
Twelve months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor represent the cornerstone of secondary prevention in acute coronary syndrome (ACS) [1–5].
INTRODUCTION
Twelve months of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor represent the cornerstone of secondary prevention in acute coronary syndrome (ACS) [1–5]. In patients undergoing surgical revascularization, the evidence is less robust because it derives mainly from subanalyses or meta-analyses of trials not specifically designed for this subgroup of patients, from registries or from small, randomized trials with surrogate non-clinical end points, such as long-term graft patency [6–9]. However, clinical practice guidelines from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery concordantly recommend 1 year of DAPT in these patients, favouring prescription of ticagrelor or prasugrel in addition to aspirin [2–5].
Despite guideline recommendations, previous reports on real-world populations showed that the rate of DAPT prescriptions given at discharge to patients with ACS undergoing surgical revascularization is low [10–12]. Reasons are likely multiple and include high bleeding risk perceived by treating physicians and lack of robust evidence supporting the use of DAPT in this setting. However, most of the published studies focusing on this topic are old, and more recent data are limited to non-European populations [10–12]. The goal of the present study was to clarify this issue in Switzerland in the era of potent P2Y12 inhibitors.
PATIENTS AND METHODS
The Acute Myocardial Infarction in Switzerland (AMIS) Plus Registry is an ongoing nationwide prospective cohort of patients admitted with a diagnosis of ACS to hospitals in Switzerland. Details of this registry have been provided elsewhere [13]. Since 1997, on a total of 106 centres treating ACS in Switzerland, 84 centres have been providing temporarily or continuously, on a voluntary basis, blinded data for patients hospitalized for ACS through standardized Internet-based or paper-based questionnaires. A list of all participating hospitals can be found at the AMIS Plus website (www.amis-plus.ch). All data are checked for completeness, plausibility, and consistency by the AMIS Plus Data Centre. Since 2010, external monitoring is regularly performed in randomly selected hospitals using randomly selected cases. The present study represents a retrospective post hoc analysis of data included in the AMIS Plus Registry.
Ethical statement
The AMIS Plus Registry has been approved by the Over-Regional Ethics Committee for Clinical Studies and the Swiss Board for Data Security (Commission d'experts du secret professionnel en matière de recherche médicale—ID number 1.05.01.10-40, date 27 May 1998). All cantonal ethics commissions approved follow-up in 2005. Data collection is conducted in accordance with the European Union Note for Guidance on Good Clinical Practice CPMP/ECH/135/95 and complies with the Declaration of Helsinki. Obtaining the patient's consent was not necessary for this study.
Patient selection
All patients with a definitive diagnosis of acute myocardial infarction (AMI) included in the AMIS Plus Registry from January 2014 to December 2019 were screened. Diagnosis of AMI required the presence of typical clinical symptoms and an increase in the creatinine kinase-MB serum level at least twice above the upper limit of normal and/or an increase of troponin (I or T) serum level above the upper limit of normal; for each biomarker, individual hospital cut-offs for diagnosis of AMI were used. AMI were further classified as non-ST-segment elevation AMI or ST-segment elevation AMI, based on electrocardiogram findings. Diagnoses conformed to the prevailing guidelines in use at the time of inclusion. Reperfusion and revascularization strategies were assessed in all screened patients. Exclusion criteria are displayed in Fig. 1.
Figure 1:
Flow chart of the study.
For all included patients, baseline clinical features were collected. Arterial hypertension, dyslipidaemia and diabetes mellitus were assumed to be present if the patient had previously been treated and/or diagnosed by a physician. A patient was defined as a current smoker if he or she had smoked at least 100 cigarettes in his or her life and was currently smoking at the time of hospitalization. An impaired left ventricular ejection fraction was defined as an angiographic left ventricular ejection fraction below 35% and/or echocardiographic left ventricular ejection fraction below 30%. Multivessel disease was defined as evidence of more than 1 involved vessel visible on the invasive coronary angiographic scan performed during the index hospitalization. Left main disease was assumed to be present if the invasive coronary angiography identified a stenosis greater than 50% in left main artery. History of atrial fibrillation (pre-existing or de novo) was recorded. Peripheral artery disease was assumed to be present if the patient had a previous diagnosis of lower extremity arterial disease or cerebrovascular disease. To account for comorbidities, the Charlson comorbidity index was calculated [14].
Data on discharge therapy were collected for all scheduled patients, including antiplatelet therapy with aspirin and P2Y12 inhibitors and oral anticoagulants (OAC). DAPT was defined as prescriptions at discharge for both aspirin and 1 P2Y12 inhibitor. Patients discharged with a prescription for OAC received either antivitamin K or direct OAC (rivaroxaban, apixaban, edoxaban or dabigatran) at a therapeutic dose. All treatments were prescribed according to current practice and guideline recommendations at the time of the index presentation; choice of treatment was left to the discretion of the treating physicians.
Bleeding complications during the index hospitalization were recorded if deemed clinically relevant by the individual physician in charge of the patient and were graded according to the Bleeding Academic Research Consortium grading system [15].
Statistical analyses
Normal distribution for continuous variables was assessed using the Kolmogorov–Smirnov test; all continuous variables were normally distributed. Categorical variables were presented as percentages; continuous variables were expressed as mean ± 1 standard deviation. Between-group comparisons for categorical variables were performed using the χ2 test or the Fisher exact test, as appropriate. Between-group comparisons for continuous variables were performed using the t-test. To assess predictors of DAPT prescriptions in the overall study population, multivariate analysis was performed using a logistic regression model. Variables included in the analysis were carefully chosen to ensure parsimony of the statistical model. Model fit was assessed using the Hosmer–Lemeshow test. To assess predictors of DAPT prescriptions in the surgical group, a preliminary univariate analysis was performed using a logistic regression model; then, variables with a significant association were tested in a multivariable logistic regression model. Odds ratios (OR) are reported with 95% confidence intervals (CIs). Temporal trends were tested using the linear-by-linear test. A P-value of <0.05 was considered significant. IBM SPSS Statistics (version 23, IBM Corp., Armonk, NY, USA) was used for statistical analyses.
RESULTS
Baseline clinical features according to revascularization strategy
A total of 16 265 eligible patients were identified and 7215 patients were excluded. Thus, 9050 patients were available for the final analysis (Fig. 1). A total of 8727 patients (96.5%) were treated with percutaneous coronary intervention (PCI), and 323 (3.5%) were treated with a coronary artery bypass graft (CABG). A diagnosis of ST-segment elevation AMI was more frequent among patients undergoing PCI (58.9% vs 24.1%; P < 0.001).
Compared with patients who have had PCI, those undergoing surgical revascularization were significantly older (67.7 ± 10 years vs 64.7 ± 12.4 years; P < 0.001), more frequently male (82% vs 77.2%; P < 0.001) and suffered more often from hypertension and diabetes (P < 0.001 for both variables). These patients presented more frequently at the hospital with an advanced Killip class (>2; 9.6% vs 4.9%; P = 0.001) and had a higher burden of multivessel and left main disease (95.3% vs 57.6% and 15.9% vs 1.8%, respectively; P < 0.001 for both variables). They also displayed a higher burden of comorbidities, as reflected in the Charlson Comorbidity Index (P < 0.001).
The overall prevalence of in-hospital bleeding complications was similar in patients who had CABG and PCI (2.2% vs 3.9%; P = 0.14); severe bleeding (Bleeding Academy Research Consortium ≥3) occurred more frequently in surgically treated patients (P = 0.04), even though the rate was below 1% in both study groups.
Baseline clinical features are summarized in Table 1.
Table 1:
Baseline characteristics according to revascularization strategy
| PCI (n = 8727) | CABG (n = 323) | P-value | |
|---|---|---|---|
| Age (years, mean ± SD) | 64.7 (12.4) | 67.7 (10.0) | <0.001 |
| Sex female (n, %) | 1989 (22.8) | 58 (18.0) | 0.042 |
| Smoking (n, %) | 3248 (41.7) | 107 (37.4) | 0.16 |
| Dyslipidaemia (n, %) | 5739 (70.9) | 167 (56.4) | <0.001 |
| Hypertension (n, %) | 5238 (62.7) | 227 (73.9) | <0.001 |
| Obesity (BMI > 30; n, %) | 1816 (21.8) | 71 (22.7) | 0.73 |
| Diabetes (n, %) | 1642 (19.6) | 106 (34.4) | <0.001 |
| Resuscitation on prior admission (n, %) | 469 (5.4) | 10 (3.1) | 0.076 |
| Killip class >2 (n, %) | 422 (4.9) | 31 (9.6) | 0.001 |
| STEMI (n, %) | 5144 (58.9) | 78 (24.1) | <0.001 |
| Multivessel disease (n, %) | 4902 (57.6) | 305 (95.3) | <0.001 |
| Left main disease (n, %) | 161 (1.8) | 51 (15.9) | <0.001 |
| Impaired LVEF (n, %) | 494 (6.2) | 36 (11.5) | 0.001 |
| Prior CAD (n, %) | 1821 (26.2) | 59 (22.8) | 0.25 |
| Atrial fibrillation (n, %) | 297 (3.6) | 19 (5.9) | 0.049 |
| Cerebrovascular diseases (n, %) | 349 (4.1) | 14 (4.4) | 0.77 |
| PAD (n, %) | 337 (3.9) | 19 (6.0) | 0.078 |
| Renal disease (n, %) | 468 (5.5) | 41 (12.9) | <0.001 |
| Cancer diseases (n, %) | 451 (5.3) | 28 (8.8) | 0.011 |
| Charlson comorbidity index >1 (n, %) | 1511 (18.8) | 91 (28.7) | <0.001 |
| Bleeding complications (n, %) | 340 (3.9) | 7 (2.2) | 0.14 |
| a Major bleeding (BARC >3; n, %) | 45/330 (35.0) | 3/6 (50.0) | 0.04 |
Percentage refers only to patients who experience bleeding complications during hospitalization and for whom Bleeding Academic Research Consortium data were available.
BARC: Bleeding Academic Research Consortium; BMI: body mass index; CABG: coronary artery bypass grafting; CAD: coronary artery disease; LVEF: left ventricular ejection fraction; PAD: peripheral artery disease; PCI: percutaneous coronary intervention; SD: standard deviation; STEMI: ST-segment elevation myocardial infarction.
Drug prescription at discharge according to revascularization strategy
Within the surgical group, 182 patients (56.3%) were discharged with DAPT. Of these, 115 patients (63.2%) received clopidogrel in addition to aspirin, 2 (1.1%) received prasugrel and 65 (35.7%) received ticagrelor. Overall, a DAPT regimen containing a new P2Y12 inhibitor was prescribed to a minority of these patients (67/115, 36.8%).
Within the percutaneous group, 8440 patients (96.7%) were discharged with a prescription for DAPT. Of these, 1495 patients (17.7%) received Clopidogrel in addition to aspirin, 2489 (29.5%) received prasugrel and 4456 (52.8%) received ticagrelor. Overall, a DAPT regimen containing a new P2Y12 inhibitor was prescribed to a majority of these patients (6945/8440, 83.2%).
The rate of OAC prescription at discharge was significantly higher in the surgical group (16.5% vs 9.4%; P < 0.001); interestingly, direct OACs were prescribed more frequently to patients undergoing PCI, even if this difference was not statistically significant (4.2% vs 2%; P = 0.085). Among patients prescribed OAC when discharged, those in the percutaneous group had a significantly higher rate of concomitant prescriptions for DAPT (85.3% vs 11.5%; P < 0.001); indeed, the majority of patients in the surgical group received only single antiplatelet therapy in addition to OAC (88.5% vs 14.2% in the percutaneous arm; P < 0.001).
Data on drugs prescription at discharge are displayed in Table 2.
Table 2:
Drugs prescribed at discharge from the hospital according to revascularization strategy
| PCI (n = 8727) | CABG (n = 323) | P-value | |
|---|---|---|---|
| Aspirin (n, %) | 8532 (97.8) | 310 (96.0) | 0.034 |
| P2Y12 inhibitors (n, %) | 8618 (98.8) | 191 (59.3) | <0.001 |
| Clopidogrel | 1624 (18.6) | 124 (38.5) | <0.001 |
| Prasugrel | 2522 (28.9) | 2 (0.6) | <0.001 |
| Ticagrelor | 4490 (51.5) | 65 (20.3) | <0.001 |
| DAPT (n, %) | 8440 (96.7) | 182 (56.3) | <0.001 |
| a DAPT (aspirin + clopidogrel) | 1495 (17.7) | 115 (63.2) | <0.001 |
| a DAPT (aspirin + prasugrel) | 2489 (29.5) | 2 (1.1) | <0.001 |
| a DAPT (aspirin + ticagrelor) | 4456 (52.8) | 65 (35.7) | <0.001 |
| a DAPT (aspirin + prasugrel or ticagrelor) | 6945 (82.3) | 67 (36.8) | <0.001 |
| OAC (n, %) | 821 (9.4) | 53 (16.5) | <0.001 |
| Antivitamin K (n, %) | 457 (5.2) | 46 (14.5) | <0.001 |
| Direct OAC (n, %) | 368 (4.2) | 7 (2) | 0.085 |
| b OAC alone (n, %) | 4 (0.5) | 0 (0) | 1.00 |
| b OAC + SAPT (n, %) | 117 (14.2) | 47 (88.5) | <0.001 |
| b OAC + DAPT (n, %) | 700 (85.3) | 6 (11.5) | <0.001 |
| Beta-blocker (n, %) | 6654 (76.3) | 266 (82.4) | 0.011 |
| ACEI/ARB (n, %) | 7556 (86.6) | 208 (64.4) | <0.001 |
| Calcium channel blocker (n, %) | 880 (10.1) | 71 (22.0) | <0.001 |
| Diuretic (n, %) | 1811 (20.8) | 110 (34.3) | 0.045 |
| Statin (n, %) | 8233 (94.6) | 296 (91.9) | <0.001 |
Percentages refer to the subgroup of patients prescribed DAPT when discharged from the hospital.
Percentages refer to the subgroup of patients prescribed OAC when discharged from the hospital.
ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor antagonist; CABG: coronary artery bypass grafting; DAPT: dual antiplatelet therapy; OAC: oral anticoagulants; PCI: percutaneous coronary intervention; SAPT: single antiplatelet therapy.
Predictors of dual antiplatelet therapy prescriptions at discharge in the overall study population
In the multivariate analysis, the following variables were significantly and independently associated with a lower likelihood of a DAPT prescription at discharge: surgical revascularization (OR 0.03, 95% CI 0.02–0.06; P < 0.001), OAC prescription at discharge (OR 0.08, 95% CI 0.06–0.11; P < 0.001), age (OR 0.97, 95% CI 0.96–0.98; P < 0.001) and impaired left ventricular ejection fraction (OR 0.65, 95% CI 0.45–0.96; P = 0.030). Results of the multivariate analysis are displayed in Table 3.
Table 3:
Predictors of dual antiplatelet therapy prescriptions at discharge in the overall study population using multivariate analysis
| OR | 95% CI | P-value | |
|---|---|---|---|
| Age (per additional years) | 0.97 | 0.96–0.98 | <0.001 |
| Female sex | 1.14 | 0.84–1.55 | 0.40 |
| Killip class >2 | 1.06 | 0.65–1.72 | 0.82 |
| Dyslipidaemia | 1.19 | 0.90–1.56 | 0.22 |
| Hypertension | 0.74 | 0.54–1.01 | 0.06 |
| Diabetes | 1.07 | 0.78–1.48 | 0.65 |
| STEMI | 1.25 | 0.95–1.63 | 0.11 |
| Multivessel disease | 1.08 | 0.80–1.46 | 0.62 |
| Impaired LVEF | 0.65 | 0.45–0.96 | <0.03 |
| CABG during index hospitalization | 0.03 | 0.02–0.06 | <0.001 |
| Atrial fibrillation | 0.88 | 0.59–1.32 | 0.54 |
| Cerebrovascular disease | 0.67 | 0.55–1.55 | 0.12 |
| PAD | 0.93 | 0.49–1.33 | 0.77 |
| Renal disease | 0.80 | 0.50–1.29 | 0.36 |
| Cancer diseases | 0.59 | 0.35–1.00 | 0.06 |
| Charlson comorbidity index >1 | 0.96 | 0.62–1.50 | 0.86 |
| OAC | 0.08 | 0.06 - 0.11 | <0.001 |
n = 6985 (77.2%).
CABG: coronary artery bypass graft; CI: confidence interval; LVEF: left ventricular ejection fraction; OAC: oral anticoagulants; OR: odds ratio; PAD: peripheral artery disease; STEMI: ST-segment elevation myocardial infarction.
Dual antiplatelet therapy at discharge in surgically treated patients
In the univariate analysis, the following variables were significantly associated with a lower likelihood of receiving a DAPT prescription at discharge: age (OR 0.94, 95% CI 0.92–0.96; P < 0.001), OAC prescription at discharge (OR 0.07, 95% CI 0.02–0.16; P < 0.001), a diagnosis of atrial fibrillation (OR 0.26, 95% CI 0.09–0.73; P = 0.011) and a diagnosis of peripheral arterial disease (OR 0.33, 95% CI 0.12–0.89; P = 0.028). However, only age (OR 0.95, 95% CI 0.92–0.97; P < 0.001) and an OAC prescription at discharge (OR 0.07, 95% CI 0.03–0.17; P < 0.001) retained a statistically significant association in the multivariate analysis. Results of the univariate analysis are summarized in Table 4.
Table 4:
Predictors of prescriptions for dual antiplatelet therapy at discharge in surgically treated patients using univariate analysis
| OR | 95% CI | P-value | |
|---|---|---|---|
| Age (per additional years) | 0.94 | 0.92–0.96 | <0.001 |
| Sex, female | 1.12 | 0.63–1.99 | 0.70 |
| Dyslipidaemia | 0.69 | 0.43–1.10 | 0.12 |
| Hypertension | 0.75 | 0.44–1.26 | 0.28 |
| Diabetes | 0.73 | 0.43–1.18 | 0.20 |
| Killip class >2 | 0.94 | 0.44–2.00 | 0.86 |
| STEMI | 0.88 | 0.52–1.46 | 0.61 |
| Multivessel disease | 1.15 | 0.41–3.24 | 0.80 |
| Left main | 1.84 | 0.97–3.49 | 0.06 |
| Impaired LVEF | 0.98 | 0.47–2.00 | 0.95 |
| Atrial fibrillation | 0.26 | 0.09–0.73 | 0.011 |
| Cerebrovascular diseases | 1.02 | 0.34–3.00 | 0.98 |
| PAD | 0.33 | 0.12–0.89 | 0.028 |
| Renal disease | 0.77 | 0.40–1.49 | 0.44 |
| Cancer | 0.74 | 0.34–1.61 | 0.45 |
| Charlson comorbidity index >1 | 0.66 | 0.40–1.08 | 0.095 |
| OAC | 0.07 | 0.02–0.16 | <0.001 |
CI: confidence interval; LVEF: left ventricular ejection fraction; OAC: oral anticoagulants; OR: odds ratio; PAD: peripheral artery disease; STEMI: ST-segment elevation myocardial infarction.
Analysis of temporal trends (2-year blocks) did not show a significant increase in the DAPT prescription rate at discharge during the study period (Fig. 2; P for trend = 0.29).
Figure 2:
Temporal trends in dual antiplatelet therapy prescription rate (expressed as percentage) at discharge in patients with acute myocardial infarction undergoing surgical revascularization (2-year blocks).
DISCUSSION
The present study provides a comprehensive picture of DAPT prescriptions given to patients who had AMI and who underwent surgical revascularization in Switzerland in the modern era of potent P2Y12 inhibitors. So far, this study represents the largest recent analysis focused on this topic in a European population. The value of the present work is further increased by the multicentre structure of the AMIS Plus Registry. Indeed, results are reliably representative of current clinical practice at a national level.
We found that surgically treated patients with AMI were significantly less likely to be discharged with a prescription for DAPT compared with patients who had PCI, despite a similar and low rate of clinically significant bleeding complications. These data are not in line with current European Society of Cardiology guidelines, which recommend DAPT prescriptions for this subgroup of patients [2–5]. Moreover, patients in the surgical group, even when discharged with a prescription for DAPT, were significantly less likely to receive a new P2Y12 inhibitor in addition to aspirin. Current guidelines support the use of more potent P2Y12 inhibitors in these patients if the risk of bleeding is not excessive [2]. In a recent meta-analysis, Verma et al. [16] found that only DAPT with more potent P2Y12 inhibitors, but not with clopidogrel, was associated with a 50% reduction in overall mortality in patients with ACS treated with CABG.
In our study, patients in the surgical group displayed a higher prevalence of atrial fibrillation and were more frequently discharged with a prescription for OAC compared with those treated by PCI. The best way to manage surgically revascularized patients with ACS with a concomitant indication for long-term OAC is still debated, and guidelines are extremely vague on this topic. The 2020 guidelines on atrial fibrillation from the European Society of Cardiology recommend dual antithrombotic therapy with OAC and clopidogrel in this subset of patients [17]. Concordantly, in our cohort, patients in the surgical group were significantly less likely to receive DAPT in addition to OAC compared with those undergoing PCI. Moreover, a prescription for OAC at discharge, but not atrial fibrillation, was significantly and independently associated with a lower likelihood of discharge with a prescription for DAPT both in the overall population and in the surgical group. However, in our multivariate model, which includes patients prescribed OAC at hospital discharge, surgical revascularization remained strongly associated with a lower likelihood of patients prescribed DAPT at hospital discharge. Moreover, the absolute rate of prescriptions for OAC at hospital discharge was relatively low in both study subgroups. Therefore, even though differences in prescriptions for OAC exist between study subgroups and have an impact on prescriptions for antiplatelet therapy, they are not sufficient to explain the observed differences in rate of patients discharged with prescriptions for DAPT.
Our data are in line with more recent observations on this topic, mostly coming from outside Europe [10–12]. Discrepancies between real-word clinical practice and guidelines are most likely related to the weakness of evidence supporting guideline recommendations. However, the results of the present study further strengthen concerns about the adequacy of secondary prevention offered to these patients in real-word clinical settings. This issue is of particular importance if we consider that these patients, frequently older, diabetic, with severe coronary artery disease and a high burden of severe comorbidities, are intrinsically at a very high risk of recurrent atherothrombotic events and cardiovascular death. In our surgical cohort, under-prescription of DAPT was homogeneous. Even patients with a higher risk of recurrent atherothrombotic events based on known comorbidities were not more likely to receive more aggressive antiplatelet therapy. Moreover, analysis of temporal trends in the DAPT prescription rate at discharge in these patients did not show significant variations over the study period. These data are in contrast with available evidence showing a progressive increase over time in the rate of DAPT prescriptions at discharge in patients with ACS [18, 19].
Interestingly, in most centres treating AMI in Switzerland, patients undergoing surgical revascularization are managed in surgical wards without the routine involvement of a cardiologist. A multidisciplinary approach could certainly stimulate discussion among treating physicians and, ultimately, increase adherence to guideline recommendations in these patients.
Limitations
Our findings must be interpreted in the context of the following limitations. This is an observational study and the presented data are retrospective with a potential uncalculated risk of selection bias. The number of patients included in the surgical arm is small compared to the number of patients included in the percutaneous group. However, the percentage of patients with AMI undergoing surgical revascularization in our cohort is in line with what we expected, based on the available literature [4, 5]. The relatively small sample size in the surgical arm could somehow limit the interpretation of analyses limited to this patient subgroup. However, the results of a multivariate analysis that included 6985 patients support the central message of the study, i.e. that patients in the surgical group are significantly less likely to receive DAPT at discharge; these results have a high statistical power and are unlikely to be due to chance or confounders. The AMIS Plus Registry does not collect surgical details; therefore, these data were not available for the analysis. Current evidence suggests that, in patients undergoing CABG, DAPT is more effective after venous grafts, endarterectomy and off-pump interventions [9]. However, the majority of studies investigating the impact of DAPT on graft patency focused on elective procedures. Therefore, in the setting of ACS, limiting the prescription of more intense antiplatelet therapy to patients receiving venous graft and/or undergoing off-pump interventions, as previously documented in other real-word experiences [10], is a strategy not supported by the current literature and not endorsed by guidelines. In this study, we only present data on DAPT prescriptions at discharge. Data on pharmacological treatment and clinical outcomes at mid- and long-term follow-up were available only for a minority of patients in the surgical group and did not allow us to perform meaningful analyses. However, as far as antiplatelet treatment prescription is concerned, current guidelines concordantly recommend early resumption of P2Y12 inhibitors after surgical revascularization in ACS [2–5]. Moreover, previous real-word data on the overall ACS population showed that, during follow-up, the rate of exposure to DAPT tends to decrease due to poor patient compliance and/or bleeding complications [19]. Even though we are aware that availability of follow-up data on clinical outcomes would have increased the interest of this paper, our goal was primarily to shed light on adherence to current guideline recommendations in the real-word arena in surgically treated patients with an AMI. Indeed, a body of evidence supporting a positive impact of DAPT on prognosis in this subset of patients is already available and is reflected by guideline recommendations. More evidence is needed to strengthen these recommendations and improve adherence to guidelines in real-word populations. However, we think that only dedicated randomized clinical trials could give a definitive answer to this still open question. Our study should be regarded as a call for action on this topic and should, in our opinion, stimulate the design of dedicated randomized clinical trials to better inform guidelines with high quality evidence and increase the confidence of the treating physicians in guidelines. Finally, based on available variables, a systematic and exhaustive estimation of bleeding risk in accordance with current recommendations by the Academic Research Consortium was not possible in our cohort [5]. However, most clinically relevant predictors of bleeding complications were included in our multivariate model. Moreover, previous studies focusing on patients with coronary artery disease have shown a prevalence of a high risk of bleeding of around 15% [20, 21]. In the LEADERS FREE trial, advanced age was by far the most common high bleeding risk factor, and 64% of trial participants were regarded as being at high risk of bleeding because they were ≥75 years of age [20]. Therefore, it is very unlikely that observed differences in antiplatelet therapy prescriptions could only be explained by differences in bleeding risk among study subgroups. Furthermore, in our study, patients undergoing surgical and percutaneous revascularization experienced a similar, low prevalence of in-hospital clinically significant bleeding.
CONCLUSION
Our study confirmed in a large nationwide cohort of patients that DAPT is still under-prescribed at discharge in patients with AMI undergoing surgical revascularization. Moreover, only a minority of surgically treated patients who are prescribed DAPT at hospital discharge receives ticagrelor or prasugrel in addition to aspirin.
These observations raise doubts about the adequacy of secondary prevention offered to patients at a high risk of recurrent atherothrombotic events in the real-word arena. Overall, efforts are necessary to clarify the role of DAPT in secondary prevention in these patients; new trials, specifically focused on this topic, would be desirable and could contribute to increasing the confidence of treating physicians in guidelines.
ACKNOWLEDGMENTS
We thank Miss Jenny Picket for English revision and professional proofreading of the manuscript.
Funding
The AMIS Plus Registry is funded by unrestricted grants from the Swiss Heart Foundation and from Abbot AG, Amgen AG, AstraZeneca AG, Bayer (Schweiz) AG, B. Boston Scientific AG, Braun Medical AG, Biotronik AG, Cordis Cardinal Health GmbH, Daiichi-Sankyo AG, Medtronic AG, Mepha Pharma AG, Novartis Pharma Schweiz AG, SIS Medical AG, Terumo, Vascular Medical GmbH and Swiss Working Group for Interventional Cardiology, all in Switzerland. The sponsors did not play any role in the design, data collection, analysis, or interpretation of the registry for the present study.
DATA SHARING STATEMENT
The authors confirm that, for approval reasons, some access restrictions apply to the data underlying the findings. Individual data used for the construction of the AMIS Plus Registry are the property of the hospitals participating in the AMIS Plus Registry and may only be made available by each hospital’s principal investigator and by the Steering Committee. This also applies to derivatives such as analysis files used for this study. However, after approval of the AMIS Plus Steering Committee and subsequent negotiation of an individual AMIS Plus module contract with the AMIS Plus Steering Committee, analysis files can be handed over to other researchers.
Conflict of interest: Hans Rickli reports institutional research grants from Biotronik, Boston, Braun, Terumo and Medtronic, all outside the submitted work. The other authors report no potential conflicts of interest.
Author contributions
Marco Roberto: Conceptualization; Data curation; Methodology; Writing – original draft. Dragana Radovanovic: Data curation; Formal analysis. Carmelo Buttà: Conceptualization; Writing – original draft. Gregorio Tersalvi: Writing – original draft. Joël Krüll: Writing – original draft. Paul Erne: Data curation; Formal analysis. Hans Rickli: Supervision; Validation. Giovanni Battista Pedrazzini: Conceptualization; Supervision; Validation. Marco Moccetti: Conceptualization; Supervision; Validation; Visualization.
Reviewer information
Interactive CardioVascular and Thoracic Surgery thanks Daniel Duerschmied, Marco Moscarelli and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.
ABBREVIATIONS
- ACS
Acute coronary syndrome
- AMI
Acute myocardial infarction
- AMIS
Acute Myocardial Infarction in Switzerland
- CABG
Coronary artery bypass graft
- CI
Confidence interval
- DAPT
Dual antiplatelet therapy
- OAC
Oral anticoagulants
- OR
Odds ratio
- PCI
Percutaneous coronary intervention
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