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‡ Drs. Mazer, S. Verma, and Ha contributed equally as senior authors. Dr Hibino is the lead author.
Affiliations
Division of Cardiac Surgery, St. Michael’s Hospital of Unity Health Toronto, Toronto, Ontario, CanadaDivision of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, CanadaDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
Division of Cardiac Surgery, St. Michael’s Hospital of Unity Health Toronto, Toronto, Ontario, CanadaDivision of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
Division of Cardiac Surgery, St. Michael’s Hospital of Unity Health Toronto, Toronto, Ontario, CanadaDivision of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, CanadaDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
Division of Cardiac Surgery, St. Michael’s Hospital of Unity Health Toronto, Toronto, Ontario, CanadaDivision of Endocrinology and Metabolism, St. Michael’s Hospital of Unity Health Toronto, Toronto, Ontario, Canada
Division of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, CanadaDivision of Cardiovascular Surgery, Toronto General Hospital Research Institute, Toronto, Ontario, CanadaPeter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
‡ Drs. Mazer, S. Verma, and Ha contributed equally as senior authors. Dr Hibino is the lead author.
Andrew C.T. Ha
Footnotes
‡ Drs. Mazer, S. Verma, and Ha contributed equally as senior authors. Dr Hibino is the lead author.
Affiliations
Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada
‡ Drs. Mazer, S. Verma, and Ha contributed equally as senior authors. Dr Hibino is the lead author.
Affiliations
Department of Anesthesia, St. Michael’s Hospital of Unity Health Toronto, Toronto, Ontario, CanadaDepartment of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, CanadaDepartment of Physiology, University of Toronto, Toronto, Ontario, Canada
Whether statins reliably reduce the risk of postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery remains controversial. We sought to determine the impact of statin use on new-onset postdischarge POAF in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized controlled trial.
Methods
We randomized 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥ 2) and no history of preoperative atrial fibrillation (AF) to 30-day continuous cardiac rhythm monitoring after discharge from cardiac surgery with a wearable, patched-based device or to usual care. The primary endpoint was the occurrence of cumulative AF and/or atrial flutter lasting for ≥ 6 minutes detected by continuous monitoring, or AF and/or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization.
Results
The 260 patients (77.4%) discharged on statins were more likely to be male (P = 0.018) and to have lower CHA2DS2-VASc scores (P = 0.011). Patients treated with statins at discharge had a 2-fold lower rate of POAF than those who were not treated with statins in the entire cohort (18.4% vs 8.1%, log-rank P = 0.0076). On multivariable Cox regression including the CHA2DS2-VASc score adjustment, statin use was associated with a lower risk of POAF (hazard ratio 0.43, 95% confidence interval: 0.25-0.98, P = 0.043). Use of statins at a higher intensity was associated with lower risk of POAF, suggestive of a dose–response effect (log-rank Ptrend = 0.0082).
Conclusions
The use of statins was associated with a reduction in postdischarge POAF risk among patients undergoing cardiac surgery. The routine use of high-intensity statin to prevent subacute POAF after discharge deserves further study.
Résumé
Contexte
L’efficacité des statines dans la réduction du risque de fibrillation auriculaire postopératoire (FAPO) chez les patients ayant subi une chirurgie cardiaque ne fait pas l’unanimité. Nous avons tenté de déterminer l’effet de l’utilisation des statines sur la survenue d’une FAPO inaugurale consécutive au congé de l’hôpital dans l’essai SEARCH-AF CardioLink-1, un essai contrôlé à répartition aléatoire sur le suivi étroit en postopératoire des arythmies cardiaques et de la fibrillation auriculaire.
Méthodologie
Nous avons réparti aléatoirement 336 patients présentant des facteurs de risque d’AVC (score CHA2DS2-VASc ≥ 2) sans antécédents de fibrillation auriculaire (FA) préopératoire dans deux groupes : les patients du premier groupe étaient équipés d’un dispositif portable sous forme de timbre pour la surveillance continue du rythme cardiaque pendant 30 jours après la sortie de l’hôpital suivant une chirurgie cardiaque; les patients du second groupe étaient suivis de façon conventionnelle. Le critère d’évaluation principal était la survenue cumulative de FA et/ou de flutter auriculaire durant ≥ 6 minutes détecté par la surveillance continue, ou la FA et/ou le flutter auriculaire confirmé par un électrocardiogramme à 12 dérivations dans les 30 jours suivant la répartition aléatoire.
Résultats
Les 260 patients (77,4 %) prenant des statines à leur congé de l’hôpital étaient plus susceptibles d’être des hommes (p = 0,018) et d’avoir un score CHA2DS2-VASc plus faible (p = 0,011). Les patients traités par des statines à leur congé de l’hôpital avaient deux fois moins de risques de présenter une FAPO que les patients ne recevant pas de statines dans l’ensemble de la cohorte (18,4 % contre 8,1 %, valeur de p calculée selon le test de Mantel-Haenszel = 0,0076). Dans une régression de Cox multivariable incluant l’ajustement du score CHA2DS2-VASc, l’utilisation des statines a été associée à un risque moindre de FAPO (rapport des risques instantanés : 0,43, intervalle de confiance à 95 % de 0,25 à 0,98; p = 0,043). L’utilisation de statines à plus fortes doses a été associée à un risque moindre de FAPO, ce qui laisse croire à un effet dose-réponse (valeur de p de tendance selon le test de Mantel-Haenszel = 0,0082).
Conclusions
L’utilisation de statines est associée à une réduction du risque de FAPO après le congé de l’hôpital chez les patients ayant subi une chirurgie cardiaque. L’utilisation systématique de statines à fortes doses pour prévenir la FAPO subaiguë après le congé d’hôpital mérite une étude plus approfondie.
Accordingly, statins have been studied as potential agents to reduce the risk of POAF in patients, owing to their anti-inflammatory and antioxidant properties.
However, clinical trials to determine the role of statins in reducing the risk of POAF after cardiac surgery have been inconclusive. Meta-analyses suggested that statins could reduce the risk of POAF among patients who underwent cardiac surgery.
However, in the Statin Therapy in Cardiac Surgery (STICS) trial, the incidence of POAF within 5 days of surgery did not differ between patients who received perioperative rosuvastatin (20 mg daily) and those who were allocated to the placebo arm.
The Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 trial (NCT02793895) randomized patients to usual care or continuous cardiac rhythm monitoring for 30 days after discharge. The trial demonstrated a significant burden of subacute POAF in patients who underwent cardiac surgery with risk factors for stroke and POAF episodes lasting less than 24 hours during hospitalization.
Effect of continuous electrocardiogram monitoring on detection of undiagnosed atrial fibrillation after hospitalization for cardiac surgery: a randomized clinical trial.
Given that this trial employed continuous cardiac rhythm monitoring for 30 days after hospital discharge, it afforded the opportunity to examine the effect of statins on the incidence of new-onset POAF during the previously understudied subacute phase post–cardiac surgery. The purpose of this study was to determine the impact of statin use on new-onset post-discharge POAF, including the dose effect of statins.
Methods
Trial design and procedures
In the SEARCH-AF trial, 336 patients with risk factors for stroke (Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke or transient ischemic attack or thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex Category [CHA2DS2-VASc] score ≥ 4 or ≥ 2 with risk factors for POAF) and no history of preoperative atrial fibrillation (AF) were randomized to usual care or continuous cardiac rhythm monitoring.
Effect of continuous electrocardiogram monitoring on detection of undiagnosed atrial fibrillation after hospitalization for cardiac surgery: a randomized clinical trial.
Risk factors for POAF included chronic obstructive pulmonary disease, sleep apnea, impaired renal function, left atrial enlargement, elevated body mass index, or combined CABG with valve repair or replacement. Patients were excluded if they had a presurgical history of AF or atrial flutter (AFL); had AF or AFL lasting 24 hours or longer after cardiac surgery; were in AF or AFL at the time of randomization; were hospitalized for 10 days or longer at the time of randomization; or received a mechanical valve or had other reasons to be treated with oral anticoagulation.
Patients randomized to enhanced cardiac rhythm monitoring were fitted with a wearable, patched-base device (SEEQ System, Medtronic, Minneapolis, MN, or a CardioSTAT System, Icentia, Québec City, QC, Canada) that provided up to 30 days of continuous cardiac rhythm monitoring after discharge from surgery. Consistent with existing guidelines, patients randomized to usual care did not undergo any protocol-mandated electrocardiogram or Holter monitoring within the first 30 days after randomization, unless clinically indicated. As mandated by the protocol, patients in both study arms underwent 14 days of continuous cardiac rhythm monitoring with a wearable patch–based monitor at 6 months.
The primary endpoint was the occurrence of cumulative AF and/or AFL lasting for ≥ 6 minutes, as detected by continuous monitoring or AF and/or AFL documented by a 12-lead electrocardiogram postdischarge within 30 days of randomization. Prespecified secondary outcomes included cumulative AF lasting 6 hours or longer and 24 hours or longer within 30 days of randomization, death, myocardial infarction, ischemic stroke, non–central nervous system thromboembolism, major bleeding, and oral anticoagulation prescription. Information on statin use and its dose was collected at the time of discharge. Data on race were collected from review of medical records.
Statistical analyses
Normality of continuous variables was assessed with the skewness and kurtosis test and with visual inspection of a histogram. Continuous variables are reported as median with interquartile range (IQR) or mean ± standard deviation (SD), as appropriate, and frequencies and percentages are used to describe categorical data. For nonparametric continuous variables, we used a Mann-Whitney U test. We used a χ2 or a Fisher’s exact text (if the frequency was < 10) to compare categorical variables. In this analysis, the exposure of interest was statin use at discharge. The association between statin use and risk of POAF was graphically displayed with Kaplan–Meier curves, and comparative analysis was performed using the log-rank test. As sensitivity analyses, we performed log-rank tests of the overall cohort (n = 318) and the continuous cardiac rhythm monitoring cohort (n = 157) after exclusion of patients who experienced POAF during hospitalization.
To examine the dose effect of statins on the primary outcome, we stratified the cohort according to the intensity of statin prescribed (high intensity: atorvastatin ≥ 40 mg daily or rosuvastatin ≥ 20 mg daily; moderate intensity: atorvastatin 10-20 mg daily, rosuvastatin 5-10 mg daily, simvastatin 20-40 mg daily, or pravastatin 40-80 mg daily; low intensity: simvastatin 10 mg daily or pravastatin 10-20 mg daily).
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
We conducted time-to-event analyses to evaluate the association between statin dose and the primary endpoint.
To adjust for baseline differences between patients who were treated and those who were not treated with statins at discharge, we performed a multivariable Cox regression analysis. The following covariates were selected: sex, CHA2DS2-VASc score, and surgery type (isolated CABG vs valve surgery with or without concomitant CABG). These variables were selected after a review of the differences in baseline characteristics between the 2 groups on univariable analysis; the covariates were selected if the P value was < 0.10 on univariable analysis. Results are reported as hazard ratio (HR) with associated 95% confidence interval (CI). A P value of < 0.05 was considered statistically significant. Statistical analyses were performed using STATA statistical software, version 17 (StataCorp, College Station, TX).
Results
Baseline characteristics
Of the 336 patients included in the SEARCH-AF CardioLink-1 trial, 260 (77.4%) received statin therapy at the time of discharge. These patients were more likely to be male (81.2% vs 68.4%, P = 0.018) and to have a lower CHA2DS2-VASc score (median [IQR]: 4.0 points [3.0, 4.0] vs 4.0 points [3.0, 4.5], P = 0.011) than those who were not discharged on statins. Of note, patients who underwent isolated CABG were more likely to be prescribed statins at discharge (78.1% vs 68.4%, P = 0.083). All other baseline characteristics were similar between the 2 groups (Table 1). The difference in POAF incidence during hospitalization between those discharged with vs without statins (2.6% vs 6.2%) was not statistically significant (P = 0.38). Among patients randomized to the enhanced cardiac rhythm monitoring arm (n = 163), statins were more likely to be prescribed to those who had undergone CABG surgery (P < 0.001). Baseline characteristics were otherwise similar between patients who were vs who were not prescribed statins at discharge (Supplemental Table S1).
Table 1Baseline demographics of the SEARCH-AF cohort, stratified by statin use
Characteristic
Statins not prescribed at discharge
Statins prescribed at discharge
P
N
76
260
Age, y
69.0 (65.0, 75.0)
68.5 (62.0, 73.0)
0.21
Sex
0.018
Female
24 (31.6)
49 (18.8)
Race
0.17
White
63 (82.9)
217 (83.5)
Asian
6 (7.9)
32 (12.3)
Other
7 (9.2)
11 (4.2)
Weight, kg
85.7 (74.8, 100.0)
88.1 (78.0, 100.8)
0.50
BMI
29.4 (26.3, 34.4)
30.8 (27.0, 34.2)
0.57
Obesity (BMI ≥ 30)
36 (47.4)
141 (54.2)
0.29
Hypertension
71 (93.4)
242 (93.1)
1.00
Hyperlipidemia
59 (77.6)
218 (83.8)
0.23
Smoking history
51 (67.1)
165 (63.5)
0.56
Alcohol (≥ 8 drinks per wk)
12 (15.8)
40 (15.4)
1.00
Sleep apnea
13 (17.1)
41 (15.8)
0.92
Heart failure
4 (5.3)
19 (7.3)
0.80
Stroke or TIA
4 (5.3)
31 (11.9)
0.13
Myocardial infarction
28 (36.8)
97 (37.3)
0.55
PCI
12 (15.8)
41 (15.8)
1.00
COPD
7 (9.2)
20 (7.7)
0.64
CHA2DS2-VASc score
4.0 (3.0, 4.5)
4.0 (3.0, 4.0)
0.011
HAS-BLED score
2.0 (2.0, 3.0)
2.0 (2.0, 3.0)
0.18
Isolated CABG
52 (68.4)
203 (78.1)
0.083
Isolated valve surgery
13 (17.1)
26 (10.0)
0.10
CABG + valve surgery
11 (14.5)
31 (11.9)
0.55
Ejection fraction, %
60.0 (53.0, 63.0)
58.0 (53.0, 62.0)
0.73
Atrial fibrillation occurring during hospitalization
2 (2.6)
16 (6.2)
0.38
Values are median (interquartile range), or n (%), unless otherwise indicated.
BMI, body mass index; CABG, coronary artery bypass grafting; CHA2DS2-VASc, Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke or transient ischemic attack or thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex Category; COPD, chronic obstructive pulmonary disease; HAS-BLED, Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly (> 65 Years), Drugs/Alcohol Concomitantly; INR, PCI, percutaneous coronary intervention; SEARCH-AF, Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation; TIA, transient ischemic attack.
In the overall cohort, statin prescription at discharge was associated with a 2-fold lower rate of the primary outcome (18.4% vs 8.1%, log-rank P = 0.076; Fig. 1). Similarly, in the subgroup of patients randomized to the enhanced cardiac rhythm monitoring arm, statin prescription at discharge was associated with a 2-fold lower rate of POAF (30.8% vs 16.1%, log-rank P = 0.036; Fig. 1). In the unadjusted analysis, statin prescription at discharge was associated with a 59% decrease in the risk of POAF within 30 days after randomization (HR 0.41, 95% CI: 0.21-0.81, P = 0.010; Table 2). The protective effect of statins was observed after adjustment of the baseline CHA2DS2-VASc score (HR, 0.46, 95% CI: 0.23, 0.91, P = 0.025), type of surgery (HR, 0.44, 95% CI: 0.22, 0.87, P = 0.018), or both the baseline CHA2DS2-VASc score and type of surgery (adjusted HR, 0.43, 95% CI: 0.25, 0.98, P = 0.043). Similar associations were observed in the sensitivity analysis, which excluded patients who had experienced POAF while hospitalized (Supplemental Fig. S1 and Supplemental Table S2).
Figure 1Association of statin therapy with cumulative incidence of postoperative atrial fibrillation within 30 days after randomization. In the overall cohort, statin prescription at discharge was associated with a 2-fold lower rate of the primary outcome (18.4% vs 8.1%, log-rank P = 0.076). In the subgroup of patients randomized to the enhanced cardiac rhythm monitoring arm, statin prescription at discharge was associated with a 2-fold lower rate of postoperative atrial fibrillation (30.8% vs 16.1%, log-rank P = 0.036).
Increasing intensity of statin therapy was associated with progressively lower rates of the primary outcome in both the entire cohort (log-rank trend P = 0.0087) and in the subgroup of the continuous cardiac rhythm monitoring arm (log-rank trend P = 0.020; Fig. 2). Due to the low number of patients treated with low-intensity statins in the continuous monitoring arm (n = 2), the data for these patients were merged with those from patients in the moderate intensity–statin arm.
Figure 2Association of statin intensity with the cumulative incidence of postoperative atrial fibrillation. Higher statin intensity was associated with lower rates of the primary outcome in the entire cohort (log-rank trend P = 0.0087) and in the subgroup of patients randomized to the continuous cardiac rhythm monitoring arm (log-rank trend P = 0.020).
No significant difference was present in the incidence of clinical outcomes (including stroke, systemic embolism, myocardial infarction, and major bleeding) based on use of statin therapy (Table 3). The total duration of AF and/or AFL was similar for patients prescribed statins at discharge (median: 310 minutes, IQR: 78.2, 674.9) and those who were not prescribed statins (median 409.3 minutes, IQR: 93.0, 1192.0, P = 0.45). The incidences of patients having a cumulative AF and/or AFL duration lasting for ≥ 6 hours and ≥ 24 hours within 30 days after discharge were similar for the 2 groups (7.3% vs 12.8%, P = 0.33) and (2.4% vs 5.1%, P = 0.59), respectively. In the continuous-monitoring arm, no difference in AF and/or AFL duration was present between the group discharged on statins and the group not discharged on statins (Supplemental Table S2).
Adjusted with the Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke, Vascular Disease, Age 65 to 74 Years, Sex Category (CHA2DS2-VASc) score and surgery type.
Reference
0.43 (0.25–0.98)
0.043
Parenthetical values are 95% confidence intervals.
∗ Adjusted with sex and surgery type.
† Adjusted with the Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke, Vascular Disease, Age 65 to 74 Years, Sex Category (CHA2DS2-VASc) score and surgery type.
This subanalysis of the SEARCH-AF CardioLink-1 Trial produced 2 major findings. First, statin prescription was associated with a 2-fold lower rate of POAF within 30 days after discharge post–cardiac surgery. Second, we observed a potential inverse dose–response relationship between the intensity of statin therapy and the incidence of POAF. Specifically, patients treated with higher statin doses had the lowest rates of POAF.
In spite of the wealth of preclinical data supporting the role of statins in decreasing inflammation, which is prominent in the postoperative period, clinical trials have yielded mixed results with respect to the role of statins on POAF.
Although smaller trials had shown reductions of in-hospital POAF with statin therapy, 2 large randomized trials failed to demonstrate the beneficial effect of statin therapy on the risk of developing POAF after cardiac surgery.
Statin recapture therapy before coronary artery bypass grafting trial: rationale and study design of a multicenter, randomized, double-blinded controlled clinical trial.
In the STICS trial (n = 1922), high-intensity rosuvastatin was not associated with a significant reduction in the rate of POAF via Holter electrocardiographic monitoring within 5 days of surgery when compared with placebo (21.1% vs 20.5%, P = 0.72).
The Short-term Atorvastatin’s Effect on Acute Kidney Injury Following Cardiac Surgery (Statin AKI) trial demonstrated that high-dose atorvastatin did not reduce the risk of POAF when compared with placebo.
A fundamental difference between the SEARCH-AF trial and these studies is that it assessed for the occurrence of POAF over a considerably longer period of time. Specifically, our trial evaluated the occurrence of POAF within the first 30 days after discharge, an aspect not examined by other studies. This approach likely allowed us to demonstrate the beneficial effect of statins on the risk of POAF after cardiac surgery. This finding is important when designing future trials to examine novel therapies on POAF after cardiac surgery.
The dose–effect response of statin intensity and POAF risk is biologically plausible, as statins attenuate inflammation, thus potentially ameliorating outcomes driven by this pathophysiological process. The ongoing Statin Recapture Therapy Before Coronary Artery Bypass Grafting Trial (StaRT-CABG) will provide additional insight on the impact of statin dosing on clinical outcomes, including AF.
Prevention of atrial fibrillation and inflammatory response after on-pump coronary artery bypass using different statin dosages: a randomized, controlled trial.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
A small randomized trial comparing 2 dosages of atorvastatin in CABG patients suggested a trend toward less POAF among patients treated with high-dose statin therapy, although this trend did not reach statistical significance.18
This hypothesis-generating analysis has several limitations. First, this was a post hoc subanalysis of a randomized controlled trial. Patients were not randomized to statin therapy, and those not on statin therapy may have had a contraindication or been intolerant to statin use. The duration of treatment with statin therapy was not controlled by the study protocol, including preoperative use of statins. Baseline CHA2DS2-VASc score values and the type of surgery significantly differed according to statin prescription, although multivariable adjustment for these variables did not affect effect estimates. Furthermore, the number of outcomes was limited, and we were not able to include more than 2 covariables in multivariable models. Finally, this study was not powered to detect for clinical outcomes; the rates of stroke and mortality were low in SEARCH-AF.
Conclusions
Among patients who underwent cardiac surgery with risk factors for stroke and no history of preoperative AF, the use of statins was associated with a reduction in the risk of POAF within 30 days after discharge. The routine use of high-intensity statins to prevent subacute POAF after discharge warrants further study.
Funding Sources
The conduct of the SEARCH-AF study was made possible with the support from the Heart and Stroke Foundation of Canada (grant G-17-0018661) and the Canadian Stroke Prevention Intervention Network, as well as unrestricted investigator-initiated grants from Bristol-Myers Squibb-Pfizer Alliance and Boehringer Ingelheim. Medtronic provided in-kind support with SEEQ devices.
Disclosures
S.V. holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management Inc, and Sanofi. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. G.B. reports receiving speaking honoraria from Medtronic, Atricure, Corcym, Edwards Lifesciences, Pfizer, and HLS Therapeutics; reports receiving research grant support from Medtronic and Angiodynamics; and reports receiving royalties from Karl Storz. H.T. reports receiving personal fees from the Canadian Medical and Surgical Knowledge Translation Research Group and S & L Solutions Event Management Inc. T.M.Y. reports receiving consulting fees from Abbott, Medtronic, BlueRock Therapeutics, Gore, and Aziyo Biologics. A.C.T.H. reports receiving lecture fees from Bayer, Bristol Myers Squibb/Pfizer alliance, and Servier. C.D.M. reports receiving advisory board honoraria and/or consulting fees from Amgen, AstraZeneca, BioAge, Boehringer Ingelheim, and PhaseBio; and reports receiving stipends for serving on DSMB from Beth Israel Deaconess Medical Center, Cerus, and Takeda. The other authors have no conflicts of interest to disclose.
Effect of continuous electrocardiogram monitoring on detection of undiagnosed atrial fibrillation after hospitalization for cardiac surgery: a randomized clinical trial.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Statin recapture therapy before coronary artery bypass grafting trial: rationale and study design of a multicenter, randomized, double-blinded controlled clinical trial.
Prevention of atrial fibrillation and inflammatory response after on-pump coronary artery bypass using different statin dosages: a randomized, controlled trial.
Ethics Statement: Each study site received approval by the local research ethics board and all patients provided written informed consent. The research reported has adhered to the relevant ethical guidelines.
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