Gender-Related Differences In Treatment Patterns And Outcomes of Patients With Atrial Fibrillation: Insights From The MISOAC-AF Trial

Abstract PurposeTo assess the gender-related differences in the treatment patterns of patients with atrial fibrillation (AF), and their prognostic value.MethodsIn this post-hoc analysis of a randomized controlled trial, 1140 hospitalized patients with comorbid AF were followed-up for a median of 2.6 years. Kaplan-Meier and multivariable Cox-regression analyses assessed the adjusted hazard ratios (aHRs) for outcomes in males and females, according to oral anticoagulation (OAC) type (vitamin K antagonist or non-vitamin K antagonist oral anticoagulants), rhythm or rate control treatment. The primary outcome was all-cause mortality and the secondary outcomes were stroke and the composite of any hospitalization or cardiovascular death. ResultsAmong 622 males and 518 females, use of OAC (61% vs 62%), rate control (56% vs 57%), and rhythm control (31% vs 28%) treatments was similar (all p>0.05). In males, use of rate control, as compared with rhythm control, was independently associated with higher rates of all-cause mortality (aHR=2.06; 95% confidence interval [CI] 1.24-3.41) and the composite of hospitalization or cardiovascular death (aHR=1.34, 95% CI 1.01-1.85). In females, use of rhythm control was significantly associated with higher rates of hospitalization-or cardiovascular mortality (aHR=1.74, 95% CI 1.03-2.94). Among genders, stroke rates were similar regardless of OAC type, rate or rhythm control treatment.ConclusionsIn patients discharged from the hospital with comorbid AF, the use of OAC, rhythm or rate control treatment was similar among genders. However, males seemed to benefit more from rhythm, whereas females from rate control treatment.

Download Full-text

Impact of rate control medications on one-year outcomes with atrial fibrillation and heart failure

European Heart Journal ◽

10.1093/eurheartj/ehab724.0493 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

R Mo ◽

Y Yang ◽

L Yu

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Adverse Events ◽

Rate Control ◽

Cardiovascular Death ◽

Control Treatment ◽

All Cause Mortality ◽

One Year ◽

Cox Analysis ◽

The Impact

Abstract Purpose Atrial fibrillation (AF) and heart failure (HF) often coexist. The impact of rate-control regimens in AF and HF patients has not been well understood. Methods In this multicenter, prospective registry with one-year follow-up, 1359 persistent or permanent AF patients got enrolled. A 1:1 HF to non-HF propensity score matching was applied to adjust for confounding variables. The primary endpoint was all-cause mortality while the secondary endpoint was defined as cardiovascular death and stroke. Multivariate Cox analysis was performed to evaluate the association between different rate-control treatment and incidence of adverse events. Results Before matching, HF patients were much younger and more likely to be female. They had a much higher prevalence of previous myocardial infarction, chronic obstructive pulmonary disease and valvular heart disease. Among 1359 participants, we identified 1016 matched patients. The number of drugs did not affect the risk of all-cause mortality in both cohorts. For non-HF patients, using calcium channel blockers (CCBs) plus digoxin had a significant higher risk of all-cause death (HR=5.703, 95% CI 1.334–24.604, p=0.019) and cardiovascular death (HR=9.558, 95% CI 2.127–42.935, p=0.003) compared with patients not receiving rate-control treatment. The use of beta-blockers, CCBs, digoxin alone, other dual or triple combinations was not related to risk of adverse events in both groups. Conclusions The combined use of CCBs and digoxin was related to increase all-cause and cardiovascular mortality in AF patients without HF but not for those with HF. However, the ideal rate-control regimen for AF and HF patients has not been established and well-designed clinical trials are needed. FUNDunding Acknowledgement Type of funding sources: None. Results of multivariate Cox analysis Kaplan-Meier curves by drug numbers

Download Full-text

Sex differences in treatment strategy and adverse outcomes among patients 75 and older with atrial fibrillation in the MarketScan database

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02419-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Vinita Subramanya ◽

J’Neka S. Claxton ◽

Pamela L. Lutsey ◽

Richard F. MacLehose ◽

Lin Y. Chen ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Sex Differences ◽

Rate Control ◽

Treatment Strategy ◽

Cox Regression ◽

Rhythm Control ◽

Adverse Outcomes ◽

Control Treatment ◽

To Receive

Abstract Background Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed. Methods We studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. Results At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34–1.49; HR men = 1.21, 95% CI 1.15–1.28, p < 0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke. Conclusion Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

Download Full-text

Comparative Effectiveness of Early Rhythm Control Versus Rate Control for Cardiovascular Outcomes in Patients With Atrial Fibrillation

Journal of the American Heart Association ◽

10.1161/jaha.121.023055 ◽

2021 ◽

Author(s):

Daehoon Kim ◽

Pil‐Sung Yang ◽

Seng Chan You ◽

Eunsun Jang ◽

Hee Tae Yu ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Atrial Fibrillation ◽

Rate Control ◽

Cardiovascular Death ◽

Population Based ◽

Cardiovascular Outcomes ◽

Rhythm Control ◽

Control Treatment ◽

Control Rhythm

Background Rhythm control is associated with better cardiovascular outcomes than usual care among patients with recently diagnosed atrial fibrillation (AF). This study investigated the effects of rhythm control compared with rate control on the incidence of stroke, heart failure, myocardial infarction, and cardiovascular death stratified by timing of treatment initiation. Methods and Results We conducted a retrospective population‐based cohort study including 22 635 patients with AF newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control in 2011 to 2015 from the Korean National Health Insurance Service database. Propensity overlap weighting was used. Compared with rate control, rhythm control initiated within 1 year of AF diagnosis decreased the risk of stroke. The point estimates for rhythm control initiated at selected time points after AF diagnosis are as follows: 6 months (hazard ratio [HR], 0.76; 95% CI, 0.66–0.87), 1 year (HR, 0.78; 95% CI, 0.66–0.93), and 5 years (HR, 1.00; 95% CI, 0.45–2.24). The initiation of rhythm control within 6 months of AF diagnosis reduced the risk of hospitalization for heart failure: 6 months (HR, 0.84; 95% CI, 0.74–0.95), 1 year (HR, 0.96; 95% CI, 0.82–1.13), and 5 years (HR, 2.88; 95% CI, 1.34–6.17). The risks of myocardial infarction and cardiovascular death did not differ between rhythm and rate control regardless of treatment timing. Conclusions Early initiation of rhythm control was associated with a lower risk of stroke and heart failure–related admission than rate control in patients with recently diagnosed AF. The effects were attenuated as initiating the rhythm control treatment later.

Download Full-text

Sex Differences in Treatment Strategy and Adverse Outcomes Among Patients 75 and Older With Atrial Fibrillation in the MarketScan Database

10.21203/rs.3.rs-852138/v1 ◽

2021 ◽

Author(s):

Vinita Subramanya ◽

J’Neka S. Claxton ◽

Pamela L. Lutsey ◽

Richard F. MacLehose ◽

Lin Y. Chen ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Sex Differences ◽

Rate Control ◽

Treatment Strategy ◽

Cox Regression ◽

Rhythm Control ◽

Adverse Outcomes ◽

Control Treatment ◽

To Receive

Abstract Background: Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed.Methods: We studied 135,850 men and 139,767 women aged ≥75 years diagnosed with AF in the MarketScan Medicare database between 2007-2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. Results: At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95%CI 1.34-1.49; HR men= 1.21, 95%CI 1.15-1.28, p <0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke. Conclusion: Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

Download Full-text

Abstract 15090: Direct Oral Anticoagulation vs Vitamin K Antagonist in Atrial Fibrillation With Liver Disease: A Systematic Review and Meta-analysis

Circulation ◽

10.1161/circ.142.suppl_3.15090 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Mahmoud El Iskandarani ◽

Islam Shatla ◽

Muhammad Khalid ◽

Bara El Kurdi ◽

Timir Paul ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Ischemic Stroke ◽

Liver Disease ◽

Vitamin K ◽

Major Bleeding ◽

Lower Risk ◽

Meta Analysis ◽

Vitamin K Antagonist ◽

All Cause Mortality

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.

Download Full-text

Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study

Thrombosis Journal ◽

10.1186/s12959-019-0211-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Emma Kirstine Laugesen ◽

Laila Staerk ◽

Nicholas Carlson ◽

Anne-Lise Kamper ◽

Jonas Bjerring Olesen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

All Cause Mortality ◽

Comparable Population

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

Download Full-text

3153Rate versus rhythm control and mortality in atrial fibrillation patients: a Danish nationwide cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.0041 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

F Dalgaard ◽

S Al-Khatib ◽

J Pallisgaard ◽

C Torp-Pedersen ◽

T B Lindhardt ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Heart Disease ◽

Control Strategy ◽

Rate Control ◽

Channel Blocker ◽

Rhythm Control ◽

All Cause Mortality ◽

Control Therapy

Abstract Background Treatment of AF patients with rate or rhythm drug therapy have shown no difference in mortality in clinical trials. However, the generalizability of these trials to real-world populations can be questioned. Purpose We aimed to investigate the all-cause and cardiovascular (CV) mortality risk in a nationwide AF cohort by treatment strategy (rate vs. rhythm) and by individual drug classes. Methods We queried the Danish nationwide registries from 2000 to 2015 to identify patients with AF. A rate control strategy included the use of one or more of the following medications: beta-blocker, digoxin, and a class-4 calcium channel blocker (CCB). A rhythm control strategy included the use of an anti-arrhythmic drug (amiodarone and class-1C). Primary outcome was all-cause mortality. Secondary outcome was CV mortality. Adjusted incidence rate ratios (IRR) were computed using Poisson regression with time-dependent covariates allowing patients to switch treatment during follow-up. Results Of 140,697 AF patients, 131,793 were on rate control therapy and n=8,904 were on rhythm control therapy. At baseline, patients on rhythm control therapy were younger (71 yrs [IQR: 62–78] vs 74 [65–82], p<0.001) more likely male (63.5% vs 51.7% p<0.001), had more prevalent heart failure (31.1% vs 19.4%, p<0.001) and ischemic heart disease (40.1% vs. 23.3%, p<0.001), and had more prior CV-related procedures; PCI (7.4% vs. 4.0% p<0.001) and CABG (15.0% vs. 2.3%, p<0.001). During a median follow up of 4.0 (IQR: 1.7–7.3) years, there were 64,653 (46.0%) deaths from any-cause, of which 27,025 (19.2%) were CVD deaths. After appropriate adjustments and compared to rate control therapy, we found a lower IRR of mortality and CV mortality in those treated with rhythm control therapy (IRR: 0.93 [95% CI: 0.90–0.97] and IRR 0.84 [95% CI: 0.79–0.90]). Compared with beta-blockers, digoxin was associated with increased risk of all-cause and CV mortality (IRR: 1.26 [95% CI: 1.24–1.29] and IRR: 1.32 [95% CI: 1.28–1.36]), so was amiodarone: IRR for all-cause mortality: 1.16 [95% CI: 1.11–1.21] and IRR for CV mortality: 1.12 [95% CI: 1.05–1.19]. Class-1C was associated with lower all-cause (0.43 [95% CI: 0.37–0.49]) and CV mortality (0.35 [95% CI: 0.28–0.44]). Figure 1. Models were adjusted for age, sex, ischemic heart disease, stroke, chronic obstructive pulmonary disease, chronic kidney disease, valvular atrial fibrillation, bleeding, diabetes, ablation, pacemaker, implantable cardioverter defibrillator, hypertension, heart failure, use of loop diuretics, calendar year, and time on treatment. Abbreviations; CCB; calcium channel blocker, PY; person years. Conclusions In a real-world AF cohort, we found that compared with rate control therapy, rhythm control therapy was associated with a lower risk of all-cause and CV mortality. The reduced mortality risk with rhythm therapy could reflect an appropriate patient selection. Acknowledgement/Funding The Danish Heart Foundation

Download Full-text

P4792Dabigatran versus vitamin K antagonists in patients with atrial fibrillation and valvular heart disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.1168 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J E Strange ◽

C Sindet-Pedersen ◽

L Staerk ◽

E L Grove ◽

T A Gerds ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Vitamin K ◽

Valvular Heart Disease ◽

Cox Regression ◽

Absolute Risk ◽

Risk Difference ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

Abstract Background Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce. Objectives To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA). Methods All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk. Results In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%). Figure 1 Conclusions In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.

Download Full-text

Rhythm control in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials

European Heart Journal ◽

10.1093/eurheartj/ehab724.0890 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S.Z Ramos ◽

A.L.D Te-Rosano

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Risk Ratio ◽

Control Strategy ◽

Rate Control ◽

Meta Analysis ◽

Rhythm Control ◽

Forest Plot ◽

Randomized Controlled ◽

All Cause Mortality

Abstract Background Atrial fibrillation (AF) is a common arrhythmia that can promote or worsen heart failure (HF). Limited data exist to guide treatment for patients with AF with HF regarding rate versus rhythm control. Purpose To perform a meta-analysis of randomized controlled trials (RCT) in the determination of the efficacy of rhythm control as compared to rate control among patients with AF and HF. Methods Extensive search of PubMed, Cochrane Library, Ovid, EMBASE, Google scholar, and Medline was done up to October 2020. Studies were limited to RCTs comparing rhythm control in patients with atrial fibrillation and heart failure with rate control. Outcome measures include all-cause mortality and cardiovascular mortality. Statistical analysis was done using Review manager V5.3. Results A total of 9800 patients were included in the pooled analysis of the comparison of rhythm control versus rate control strategy in patients with AF and HF. All pooled analyses were done using random effects model. The pooled risk ratio for all-cause mortality of rate control vs rhythm control did not achieve significance at 1.15, with 95% CI 0.91 to 1.45, and p=0.24. There was statistically significant heterogeneity across the two studies with I2 of 54% and p=0.02 (Figure 1A). The pooled risk ratio for cardiovascular mortality in rate control strategy vs rhythm control is 1.19, with 95% CI 0.94 to 1.50, and p=0.15 (Figure 1B). Eight trials with 9987 participants reported stroke. The pooled risk ratio of stroke in rate control vs rhythm control is 1.11, with 95% CI 0.84 to 1.46, and p=0.47 (Figure 1C). The 95% CI for the pooled risk ratio cross 1.00, indicating an equivocal result. Our results do not indicate statistical heterogeneity across the studies with I2 of 28% and p=0.27. Seven trials with 8311 participants reported bleeding. The pooled risk ratio of hospitalization for bleeding in rate control vs rhythm control is 1.18, with 95% CI 0.81 to 1.73, and p=0.39 (Figure 1D). Thus, we have insufficient evidence to demonstrate whether rate or rhythm control have significantly higher or lower risk for bleeding. Four trials with 8468 participants reported hospitalization rate. The pooled risk ratio of hospitalization in rate control compared to rhythm control is 0.96, with 95% CI 0.86 to 1.07, and p=0.42 (Figure 1E). None of the studies individually showed statistically significant differences but AF–CHF showed benefit of rate control in the first year after enrolment (p=0.001) and a tendency favouring rate control (p=0.06) when the study was analysed in full length except for AF-CHF. Conclusion Among patients with AF and concomitant HF, there is no sufficient evidence between rate and rhythm control strategies in their effects to rates of mortality and major clinical outcomes; therefore, choosing an appropriate therapeutic strategy should consider individual variations such as patient preferences, comorbidities, and treatment cost. FUNDunding Acknowledgement Type of funding sources: None. Forest Plot A–C Forest Plot D–E

Download Full-text

Bleeding and thromboembolism due to drug-drug interactions with non-vitamin K antagonist oral anticoagulants—a Swedish, register-based cohort study in atrial fibrillation outpatients

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-03015-7 ◽

2020 ◽

Author(s):

Johan Holm ◽

Buster Mannheimer ◽

Rickard E Malmström ◽

Erik Eliasson ◽

Jonatan D Lindh

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Ischemic Stroke ◽

Vitamin K ◽

Cox Regression ◽

Oral Anticoagulants ◽

Outcome Data ◽

Vitamin K Antagonist ◽

Drug Register ◽

Increased Risk

Abstract Purpose To study the association between interacting drugs and bleeding or thromboembolism in atrial fibrillation outpatients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods Population-based cohort study of outpatients treated with NOACs in Sweden from 2008 to 2017. Patients with atrial fibrillation and newly initiated NOAC treatment were identified in the Prescribed Drug Register. Comorbidities and outcome data were retrieved from the Patient Register and the Cause of Death Register. Cox-regression analyses were performed to evaluate the primary endpoints any severe bleed and ischemic stroke/transient ischemic attack/stroke unspecified during the first six months of treatment. Secondary endpoints were gastrointestinal bleeding, intracranial bleeding, ischemic stroke, and venous thromboembolism. Results Increased risk of any severe bleed was found when NOAC treatment, and drugs with pharmacodynamic effect on bleeding were combined, compared to NOAC only. An increased risk with these combinations was evident for apixaban (hazard ratio (HR) 1.47; 95% CI 1.33–1.63), rivaroxaban (HR 1.7; 95% CI 1.49–1.92), and dabigatran (HR 1.26; 95% CI 1.05–1.52). For apixaban, there was an increased risk of any severe bleed when combined with CYP3A4 and/or P-glycoprotein (P-gp) inhibitors (HR 1.23; 95% CI 1.01–1.5). The use of inducers of CYP3A4 and/or P-gp was low in this cohort, and effects on ischemic stroke/TIA/stroke unspecified could not be established. Conclusion Increased risk of bleeding was seen for pharmacodynamic and pharmacokinetic interactions with NOACs. Prescribers need to be vigilant of the effect of interacting drugs on the risk profile of patients treated with NOACs.

Download Full-text