The preventive effect of statin therapy on new-onset and recurrent atrial fibrillation in patients not undergoing invasive cardiac interventions

Bang, Casper N.; Greve, Anders M.; Abdulla, Jawdat; Køber, Lars; Gislason, Gunnar; Wachtell, Kristian

doi:10.1016/j.ijcard.2012.08.056

Cited by 30 publications

(22 citation statements)

References 58 publications

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“…For one, the increased use of statins in this patient group may contribute to the lower risk of inappropriate therapy, as previously described, 13,33,34 but our results were consistent even after adjustment for statin use in the multivariate analyses. In addition, statin use might generally be related to a lower risk of atrial fibrillation, a reduction in atherosclerotic progression, and effects on serum lipids 35,36 rather than a reduced risk of SVT and sinus tachycardia, as we observed in this trial in patients with diabetes mellitus. Second, patients with diabetes mellitus may be more immobile and sedentary because of ischemia of the lower extremities, peripheral neuropathy, and higher weight; consequently, exerciseinduced sinus tachycardia is less frequent among these patients.…”

Section: Discussionsupporting

confidence: 49%

Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial

et al. 2013

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T he Multicenter Automatic Defibrillator Implantation TrialReduce Inappropriate Therapy (MADIT-RIT) showed that innovative implantable cardioverter-defibrillator (ICD) programming was associated with a reduction in inappropriate therapy and mortality.1 The MADIT-RIT trial randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia (VT) zone of 170 to 199 bpm, high-rate cutoff with a VT zone ≥200 bpm, or 60-seconddelayed therapy during a VT zone of 170 to 199 bpm. Clinical Perspective on p 701Background-The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown. Methods and Results-The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio,1.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not. Conclusions-Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Ruwald et al Diabetes Mellitus and ICD Programming and Therapy 695Diabetes mellitus is a growing burden to the healthcare system. It affects 25.8 million of the US population (8.3%) and is a major cause of heart disease and stroke. In ICD patients, diabetes mellitus is associated with an increased risk of hospitalization for heart failure, sudden cardiac death, and all-cause mortality 2-6 ; however, the association between diabetes mellitus and inappropriate and appropria...

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Section: Discussionsupporting

confidence: 49%

Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial

et al. 2013

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“…Furthermore, the possibility that statins might have a beneficial anti-inflammatory effect on the genesis and persistence of AF/AFL has not been consistently borne out in multiple studies and meta-analyses. 20,21 …”

Section: Discussionmentioning

confidence: 99%

Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT

Haywood

Davis²,

Piller³

et al. 2017

Journal of the National Medical Association

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Aims Limited information is available on long-term antihypertensive and lipid-lowering therapy effects on hypertensive patients with atrial fibrillation/flutter (AF/AFL) compared to those without. AF/AFL at baseline or during the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (mean follow-up 4.9 years) markedly increased risk of stroke, heart failure, CHD, and all-cause mortality. We aimed to determine if AF/AFL continued to impact outcomes during post-trial follow-up (mean 3.8 years). Methods Patients were randomized to chlorthalidone, amlodipine, or lisinopril, and to pravastatin vs. placebo in the lipid-lowering trial (LLT). Of 31,473 available subjects, AF/AFL occurred in 854; 383/14,371 chlorthalidone (2.7%), 247/8,565 amlodipine (2.9%), and 224/8,537 lisinopril (2.6%). Post-hoc analyses utilized administrative databases for post-trial data. Individuals with AF/AFL were compared to those without during post-trial. Outcomes were analyzed by treatment groups for the antihypertensive and LLT trials. Results Among 854 AF/AFL participants, 491 (57.5%) died: 220 in-trial, 271 post-trial. Ten-year all-cause mortality rates for those with in-trial AF/AFL were similar for chlorthalidone and lisinopril, but lower for amlodipine (68, 66, and 49 per 100 persons, respectively); adjusted HR for amlodipine vs. chlorthalidone was 0.68 (95% Cl, 0.54–0.87). Ten-year all-cause mortality rates were 57 vs. 65 per 100 persons (pravastatin vs. usual care); non-CVD mortality rates, 18 vs. 39 per 100 persons (pravastatin vs. usual care) (adjusted HR=0.46, 95% CI, 0.24–0.86). Conclusion Post-trial follow-up revealed continued deleterious AF/AFL effects. The amlodipine (ALLHAT) and pravastatin (ALLHAT-LLT) treatment groups showed lower all-cause and non-CVD mortality compared to the chlorthalidone and usual-care groups, respectively.

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“…48,49 Statins also failed to prevent AF recurrence after cardioversion 47 and catheter ablation. 50 Nevertheless, the perioperative use of statins has reduced POAF incidence, lowered serum inflammatory biomarkers, and attenuated reperfusion myocardial injury after cardiac surgery.…”

Section: Anti-inflammatory Interventions In Afmentioning

confidence: 99%

Role of Inflammation in Atrial Fibrillation Pathophysiology and Management

Harada

Wagoner

Nattel

2015

Circ J

386

290

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Atrial fibrillation (AF) is the most common clinically relevant arrhythmia, but the methods available for treating AF and its complications (of which the most important is thrombogenesis), as well as for assessing AF risk and underlying pathophysiology, are largely limited. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. That evidence includes elevated serum levels of inflammatory biomarkers in AF subjects, the expression of inflammatory markers in cardiac tissues of AF patients and animal models of AF, and beneficial effects of anti-inflammatory drugs in experimental AF paradigms. Inflammation is suggested to be linked to various pathological processes, such as oxidative stress, apoptosis, and fibrosis, that promote AF substrate formation. Inflammation has also been associated with endothelial dysfunction, platelet activation, and coagulation cascade activation, leading to thrombogenesis. Thus, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. Here, we review the evidence for a role of inflammation and inflammatory biomarkers in the risk management and treatment of AF. We also summarize the current knowledge of inflammation-dependent cellular and molecular mechanisms in AF pathophysiology and their potential as therapeutic targets.

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The preventive effect of statin therapy on new-onset and recurrent atrial fibrillation in patients not undergoing invasive cardiac interventions

Cited by 30 publications

References 58 publications

Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial

Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial

Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT

Role of Inflammation in Atrial Fibrillation Pathophysiology and Management

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