Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study

Background

Atrial fibrillation is an important cause of morbidity and mortality worldwide, but scant data are available for long-term outcomes in individuals outside North America or Europe, especially in primary care settings.

Methods

We did a cohort study using a prospective registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis. 15 400 individuals were enrolled to determine the occurrence of death and strokes (the primary outcomes) in this cohort over eight geographical regions (North America, western Europe, and Australia; South America; eastern Europe; the Middle East and Mediterranean crescent; sub-Saharan Africa; India; China; and southeast Asia) 1 year after attending the emergency department. Patients from North America, western Europe, and Australia were used as the reference population, and compared with patients from the other seven regions

Findings

Between Dec 24, 2007, and Oct 21, 2011, we enrolled 15 400 individuals to the registry. Follow-up was complete for 15 361 (99·7%), of whom 1758 (11%) died within 1 year. Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis (377 [6%] of 6825 patients vs 1381 [16%] of 8536, p<0·0001). Twice as many patients had died by 1 year in South America (192 [17%] of 1132) and Africa (225 [20%] of 1137) compared with North America, western Europe, and Australia (366 [10%] of 3800, p<0·0001). Heart failure was the most common cause of death (519 [30%] of 1758); stroke caused 148 (8%) deaths. 604 (4%) of 15361 patients had had a stroke by 1 year; 170 (3%) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 (5%) of 8536 for whom it was a secondary diagnosis (p<0·0001). The highest number of strokes occurred in patients in Africa (89 [8%] of 1137), China (143 [7%] of 2023), and southeast Asia (88 [7%] of 1331) and the lowest occurred in India (20 [<1%] of 2536). 94 (3%) of 3800 patients in North America, western Europe, and Australia had a stroke.

Interpretation

Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important. Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation.

Funding

Boehringer Ingelheim.

The Lancet, Volume 388, No. 10050, p1161–1169, 17 September 2016

Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis

Objective To quantify the association between atrial fibrillation and cardiovascular disease, renal disease, and death.

Design Systematic review and meta-analysis.

Data sources Medline and Embase.

Eligibility criteria Cohort studies examining the association between atrial fibrillation and cardiovascular disease, renal disease, and death. Two reviewers independently extracted study characteristics and the relative risk of outcomes associated with atrial fibrillation: specifically, all cause mortality, cardiovascular mortality, major cardiovascular events, any stroke, ischaemic stroke, haemorrhagic stroke, ischaemic heart disease, sudden cardiac death, congestive heart failure, chronic kidney disease, and peripheral arterial disease. Estimates were pooled with inverse variance weighted random effects meta-analysis.

Results 104 eligible cohort studies involving 9 686 513 participants (587 867 with atrial fibrillation) were identified. Atrial fibrillation was associated with an increased risk of all cause mortality (relative risk 1.46, 95% confidence interval 1.39 to 1.54), cardiovascular mortality (2.03, 1.79 to 2.30), major cardiovascular events (1.96, 1.53 to 2.51), stroke (2.42, 2.17 to 2.71), ischaemic stroke (2.33, 1.84 to 2.94), ischaemic heart disease (1.61, 1.38 to 1.87), sudden cardiac death (1.88, 1.36 to 2.60), heart failure (4.99, 3.04 to 8.22), chronic kidney disease (1.64, 1.41 to 1.91), and peripheral arterial disease (1.31, 1.19 to 1.45) but not haemorrhagic stroke (2.00, 0.67 to 5.96). Among the outcomes examined, the highest absolute risk increase was for heart failure. Associations between atrial fibrillation and included outcomes were broadly consistent across subgroups and in sensitivity analyses.

Conclusions Atrial fibrillation is associated with an increased risk of death and an increased risk of cardiovascular and renal disease. Interventions aimed at reducing outcomes beyond stroke are warranted in patients with atrial fibrillation.

BMJ 2016;354:i4482

Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study

Objective To estimate the association between guideline recommended drugs and death in older adults with multiple chronic conditions.

Design Population based cohort study. Setting Medicare Current Beneficiary Survey cohort, a nationally representative sample of Americans aged 65 years or more. Participants 8578 older adults with two or more study chronic conditions (atrial fibrillation, coronary artery disease, chronic kidney disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, and thromboembolic disease), followed through 2011.

Exposures Drugs included β blockers, calcium channel blockers, clopidogrel, metformin, renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazides; and warfarin.

Main outcome measure Adjusted hazard ratios for death among participants with a condition and taking a guideline recommended drug relative to participants with the condition not taking the drug and among participants with the most common combinations of four conditions.

Results Over 50% of participants with each condition received the recommended drugs regardless of coexisting conditions; 1287/8578 (15%) participants died during the three years of follow-up. Among cardiovascular drugs, β blockers, calcium channel blockers, RAS blockers, and statins were associated with reduced mortality for indicated conditions. For example, the adjusted hazard ratio for β blockers was 0.59 (95% confidence interval 0.48 to 0.72) for people with atrial fibrillation and 0.68 (0.57 to 0.81) for those with heart failure. The adjusted hazard ratios for cardiovascular drugs were similar to those with common combinations of four coexisting conditions, with trends toward variable effects for β blockers. None of clopidogrel, metformin, or SSRIs/SNRIs was associated with reduced mortality. Warfarin was associated with a reduced risk of death among those with atrial fibrillation (adjusted hazard ratio 0.69, 95% confidence interval 0.56 to 0.85) and thromboembolic disease (0.44, 0.30 to 0.62). Attenuation in the association with reduced risk of death was found with warfarin in participants with some combinations of coexisting conditions.

Conclusions Average effects on survival, particularly for cardiovascular study drugs, were comparable to those reported in randomized controlled trials but varied for some drugs according to coexisting conditions. Determining treatment effects in combinations of conditions may guide prescribing in people with multiple chronic conditions.

Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study by Mary E Tinetti, et al. BMJ 2015; 351 :h4984 (Published 02 October 2015)

Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation

Importance The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is used clinically for stroke risk stratification in atrial fibrillation (AF). Its usefulness in a population of patients with heart failure (HF) is unclear.

Objective To investigate whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in a cohort of patients with HF with and without AF.

Design, Setting, and Population Nationwide prospective cohort study using Danish registries, including 42,987 patients (21.9% with concomitant AF) not receiving anticoagulation who were diagnosed as having incident HF during 2000-2012. End of follow-up was December 31, 2012. Exposures Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk), stratified by concomitant AF at baseline. Analyses took into account the competing risk of death.

Main Outcomes and Measures Ischemic stroke, thromboembolism, and death within 1 year after HF diagnosis.

Results In patients without AF, the risks of ischemic stroke, thromboembolism, and death were 3.1% (n=977), 9.9% (n=3187), and 21.8% (n=6956), respectively; risks were greater with increasing CHA2DS2-VASc scores as follows, for scores of 1 through 6, respectively: (1) ischemic stroke with concomitant AF: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%; without concomitant AF: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7% and (2) all-cause death with concomitant AF: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%; without concomitant AF: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%. At high CHA2DS2-VASc scores (≥4), the absolute risk of thromboembolism was high regardless of presence of AF (for a score of 4, 9.7% vs 8.2% for patients without and with concomitant AF, respectively; overall P<.001 for interaction). C statistics and negative predictive values indicate that the CHA2DS2-VASc score performed modestly in this HF population with and without AF (for ischemic stroke, 1-year C statistics, 0.67 [95% CI, 0.65-0.68] and 0.64 [95% CI, 0.61-0.67], respectively; 1-year negative predictive values, 92% [95% CI, 91%-93%] and 91% [95% CI, 88%-95%], respectively).

Conclusions and Relevance Among patients with incident HF with or without AF, the CHA2DS2-VASc score was associated with risk of ischemic stroke, thromboembolism, and death. The absolute risk of thromboembolic complications was higher among patients without AF compared with patients with concomitant AF at high CHA2DS2-VASc scores. However, predictive accuracy was modest, and the clinical utility of the CHA2DS2-VASc score in patients with HF remains to be determined.

Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation by Line Melgaard, et al. JAMA. 2015;314(10):1030-1038