Ole Ahlehoff

Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study

It was the aim of this study to determine the efficacy and safety of vitamin K antagonists (VKAs) and acetylsalicylic acid (ASA) in patients with non-valvular atrial fibrillation (AF), with separate analyses according to predicted thromboembolic and bleeding risk. By individual level-linkage of nationwide registries, we identified all patients discharged with non-valvular AF in Denmark (n=132,372). For every patient, the risk of stroke and bleeding was calculated by CHADS₂, CHA₂DS₂-VASc, and HAS-BLED. During follow-up, treatment with VKA and ASA was determined time-dependently. VKA consistently lowered the risk of thromboembolism compared to ASA and no treatment; the combination of VKA+ASA did not yield any additional benefit. In patients at high thromboembolic risk, hazard ratios (95% confidence interval) for thromboembolism were: 1.81 (1.73-1.90), 1.14 (1.06-1.23), and 1.86 (1.78-1.95) for ASA, VKA+ASA, and no treatment, respectively, compared to VKA. The risk of bleeding was increased with VKA, ASA, and VKA+ASA compared to no treatment, the hazard ratios were: 1.0 (VKA; reference), 0.93 (ASA; 0.89-0.97), 1.64 (VKA+ASA; 1.55-1.74), and 0.84 (no treatment; 0.81-0.88), respectively. There was a neutral or positive net clinical benefit (ischaemic stroke vs. intracranial haemorrhage) with VKA alone in patients with a CHADS₂ score of ≥ 0, and CHA₂DS₂-VASc score of ≥ 1. This large cohort study confirms the efficacy of VKA and no effect of ASA treatment on the risk of stroke/thromboembolism. Also, the risk of bleeding was increased with both VKA and ASA treatment, but the net clinical benefit was clearly positive, in favour of VKA in patients with increased risk of stroke/thromboembolism.

The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study

Objectives To examine in a nationwide cohort whether the risk of myocardial infarction (MI) in patients with rheumatoid arthritis (RA) is comparable to the risk in patients with diabetes mellitus (DM). Methods The study included the entire Danish population followed from 1 January 1997 until 31 December 2006. Through individual level-linkage of nationwide administrative registers, the authors identified subjects who developed RA and DM. The risk of MI was analysed using multivariable Poisson regression models including data on cardioprotective drugs, comorbidity and socioeconomic status. Results From a total of 4 311 022 individuals included in the cohort, 10 477 and 130 215 individuals developed RA and DM respectively. The overall incidence rate ratio (IRR) of MI in RA was 1.7 (95% CI 1.5 to 1.9), which was similar to the risk in DM (1.7 (1.6 to 1.8); p=0.64 for difference). The risk was significantly increased in all groups when stratifying on age and gender, with higher RRs in younger patients. This was especially pronounced in women <50 years with RA or DM, who were subject to a sixfold increase in RR. The RA-related risk of MI was unaffected by the duration of pharmacological RA treatment and corresponded to the overall risk of MI observed in non-RA subjects, who were on the average 10 years older. Conclusions RA is associated with the same risk of MI as DM, and the risk of MI in RA patients generally corresponded to the risk in non-RA subjects 10 years older.

Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use: A Nationwide Cohort Study

BACKGROUNDnControversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel.nnnOBJECTIVEnTo examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction.nnnDESIGNnA nationwide cohort study based on linked administrative registry data.nnnSETTINGnAll hospitals in Denmark.nnnPATIENTSnAll patients discharged after first-time myocardial infarction from 2000 to 2006.nnnMEASUREMENTSnThe primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year.nnnRESULTSnOf 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72).nnnLIMITATIONSnUnmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible.nnnCONCLUSIONnProton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.

Risk of atrial fibrillation and stroke in rheumatoid arthritis: Danish nationwide cohort study

Objectives To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke. Design Longitudinal nationwide register based cohort study. Setting Inpatient and outpatient hospital care in Denmark from 1997 to 2009. Participants Entire Danish population aged over 15 years without rheumatoid arthritis, atrial fibrillation, or stroke before 1997. Participants with rheumatoid arthritis were identified by individual level linkage of diagnoses and rheumatoid arthritis treatment. Main outcome measures Rates of atrial fibrillation and stroke. Results Of 4u2009182u2009335 participants included in the cohort, 18u2009247 were identified as having rheumatoid arthritis during follow-up, with a mean age at disease onset of 59.2 years and a median follow-up of 4.8 years. A total of 156u2009484 people, including 774 with rheumatoid arthritis, were diagnosed as having atrial fibrillation (age and sex matched event rates of 8.2 per 1000 person years in rheumatoid arthritis patients and 6.0 per 1000 person years in the general population), with an adjusted incidence rate ratio of 1.41 (95% confidence interval 1.31 to 1.51). In addition, 165u2009343 people, including 718 with rheumatoid arthritis, had a stroke (7.6 per 1000 person years in rheumatoid arthritis and 5.7 per 1000 person years in the general population), with a resultant rate ratio of 1.32 (1.22 to 1.42). For both atrial fibrillation and stroke, relative risks were increased in all strata based on thirds of sex and age, with higher relative risks in younger patients but higher absolute risk differences in older patients. Conclusions Rheumatoid arthritis was associated with an increased incidence of atrial fibrillation and stroke. The novel finding of increased risk of atrial fibrillation in rheumatoid arthritis suggests that this arrhythmia is relevant in cardiovascular risk assessment of these patients.

Initiation and adherence to secondary prevention pharmacotherapy after myocardial infarction in patients with rheumatoid arthritis: a nationwide cohort study

Objectives To examine whether rheumatoid arthritis (RA) is associated with less optimal secondary prevention pharmacotherapy after first-time myocardial infarction (MI). Methods The authors identified all patients with first-time MI in the Danish National Patient Register from 2002 to 2009 and gathered individual level information including pharmacy records from nationwide registers. Initiation of standard care post-MI secondary prevention drugs, that is, aspirin, β-blockers, clopidogrel, renin angiotensin system (RAS) blockers and statins, was determined after discharge. In addition, adherence to each drug was evaluated as the proportion of patients on treatment during follow-up and time to first treatment gap. Results A total of 66 107 MI patients (37% women) were discharged alive; 877 were identified as RA patients (59% women). Thirty days after discharge, RA was associated with significantly lower initiation of aspirin (OR 0.80 (0.67–0.96)), β-blockers (0.77 (0.65–0.92)) and statins (0.69 (0.58–0.82)), while initiation of RAS blockers (0.80 (0.57–1.11)) and clopidogrel (0.88 (0.75–1.02)) was non-significantly reduced. These estimates were virtually unchanged at day 180 and the results were corroborated by Cox regression analyses. Adherence to statins was lower in RA patients relative to non-RA patients (HR for treatment gap of 90 days: 1.26 (1.07–1.48)), while no significant differences were found in adherence to the other drugs. Conclusions In this nationwide study of unselected patients with first-time MI, a reduced initiation of secondary prevention pharmacotherapy was observed in RA patients. This undertreatment may contribute to the increased cardiovascular disease burden in RA and the underlying mechanisms warrant further study.

Psoriasis and New-onset Depression: A Danish Nationwide Cohort Study.

Psoriasis is associated with an increased risk of depression, but results are inconsistent. This study examined the risk of new-onset depression in patients with psoriasis in a nationwide Danish cohort including some 5 million people in the period 2001-2011. A total of 35,001 patients with mild psoriasis and 7,510 with severe psoriasis were identified. Incidence rates per 1,000 person-years and incidence rate ratios (IRRs) were calculated. Incidence rates for depression were 20.0 (95% confidence interval 19.9-20.0), 23.9 (23.1-24.7) and 31.6 (29.5-33.8) for the reference population, mild, and severe psoriasis, respectively. Adjusted for age, sex, and inclusion year, IRRs were 1.08 (1.04-1.12) in mild and 1.36 (1.27-1.46) in severe psoriasis. After adjustment for comorbidity, the IRR was significant in only patients <u200950 years with severe psoriasis (IRR 1.23 (1.03-1.46)). In conclusion, the risk of new-onset depression in psoriasis is mediated primarily by comorbidities, except in younger individuals with severe psoriasis, in whom psoriasis itself may be a risk factor.

Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events: nationwide cohort study

Objective To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue. Design Nationwide register based cohort study. Setting All hospitals in Denmark. Population All 3322 women aged 40 years or over who survived 30 days after a myocardial infarction and were prescribed hormone replacement therapy at the time of myocardial infarction in the period 1997 to 2008. Main outcome measures Reinfarction, cardiovascular mortality, and all cause mortality 30 to 360 days after discharge. Results A total of 282 (8.5%) women had a reinfarction, 218 (6.6%) died of cardiovascular causes, and 357 (10.7%) died of any cause during follow-up. Women who discontinued overall hormone replacement therapy in the first year after myocardial infarction did not have a significantly different risk of reinfarction (hazard ratio 0.90, 95% confidence interval 0.68 to 1.19), cardiovascular mortality (1.21, 0.90 to 1.62), or all cause mortality (1.22, 0.97 to 1.53) than women who continued use. However, discontinuation of vaginal oestrogen was associated with a lower risk of reinfarction (hazard ratio 0.54, 0.34 to 0.86). Conclusion No certain conclusions can be drawn regarding increased or decreased risk of adverse cardiovascular events with continuing hormone replacement therapy after myocardial infarction. The results rule out neither a modest benefit nor a worrisome increase in risk. These figures may be valuable when a possible cardiovascular risk of hormone replacement therapy needs to be balanced with menopausal symptoms for the individual patient.

Prognosis After First-Time Myocardial Infarction in Patients With Inflammatory Bowel Disease According to Disease Activity Nationwide Cohort Study

Background—Inflammatory bowel disease (IBD) is associated with increased cardiovascular risk. We examined the effect of active IBD on major adverse cardiovascular outcomes after myocardial infarction (MI). Methods and Results—In nationwide registries, we identified 86 790 patients with first-time MI from the period 2002 to 2011. A total of 1030 patients had IBD, and we categorized their disease activity stages into either flare (120 days), persistent (>120 days) activity, or remission. Short-term mortality was estimated in a logistic regression-model, whereas risk of recurrent MI, all-cause mortality, and a composite of recurrent MI, cardiovascular death, and stroke were estimated by Cox regression-models. Odds ratio of death during hospitalization or within 30 days of discharge (n=13 339) corresponded to 3.29 (95% confidence interval [CI], 1.98–5.45) for patients in IBD flares, 1.62 (95% CI, 0.95–2.77) for persistent activity, and 0.97 (95% CI, 0.78–1.19) for remission when compared with the non-IBD group. Among 73 451 patients, including 863 with IBD, alive 30 days after discharge, IBD was associated with hazard ratios of 1.21 (95% CI, 0.99–1.49) for recurrent MI, 1.14 (95% CI, 1.01–1.28) for all-cause mortality, and 1.17 (95% CI, 1.03–1.34) for the composite end point. When compared with the non-IBD group, IBD flares, in particular, were associated with increased risks of recurrent MI (hazard ratio, 3.09; 95% CI, 1.79–5.32), all-cause mortality (hazard ratio, 2.25; 95% CI, 1.61–3.15), and the composite end point (hazard ratio, 2.04; 95% CI, 1.35–3.06), whereas no increased risk was identified in remission. Conclusions—Active inflammatory bowel disease worsens prognosis after MI, in particular, in relation with flares.

Psoriasis and cardiovascular events: updating the evidence

So far, systematic reviews have suggested an increased risk of cardiovascular diseases (CVD) in psoriatic patients, though some results have been conflicting. The aim of this study was to update the current level of evidence through a systematic search in MEDLINE, EMBASE and Cochrane Central Register databases. In total, 13 high-quality observational studies estimating the incidence of CVD were included. Patients with mild psoriasis had an increased risk of stroke [Hazard ratio (HR)u2009=u20091.10, 95% CI: 1.0–1.19] and myocardial infarction (MI) (HRu2009=u20091.20, 95% CI: 1.06–1.35), but not cardiovascular death. The risks of both stroke (HRu2009=u20091.38, 95% CI: 1.20–1.60), MI (HRu2009=u20091.70, 95% CI: 1.18–2.43) and cardiovascular death (HRu2009=u20091.37, 95% CI: 1.13–1.67) were increased in patients with severe psoriasis. In conclusion, this updated meta-analysis confirmed that patients with psoriasis have an increased risk of CVD, especially those with severe psoriasis.

Anthracycline-induced cardiomyopathy: Favourable effects of cardiac resynchronization therapy

We report a case of severe refractory congestive heart failure after anthracycline chemotherapy in a patient with a narrow QRS interval on the electrocardiogram and echocardiographic evidence of left ventricular dyssynchrony, where cardiac resynchronization therapy resulted in normalization of left ventricular ejection fraction and marked symptomatic relief.