Charlotte Mérie

Association of Warfarin Therapy Duration After Bioprosthetic Aortic Valve Replacement With Risk of Mortality, Thromboembolic Complications, and Bleeding

CONTEXT The need for anticoagulation after surgical aortic valve replacement (AVR) with biological prostheses is not well examined. OBJECTIVE To perform a nationwide study of the association of warfarin treatment with the risk of thromboembolic complications, bleeding incidents, and cardiovascular deaths after bioprosthetic AVR surgery. DESIGN, SETTING, AND PARTICIPANTS Through a search in the Danish National Patient Registry, 4075 patients were identified who had bioprosthetic AVR surgery performed between January 1, 1997, and December 31, 2009. Concomitant comorbidity and medication were retrieved. Poisson regression models were used to determine risk. MAIN OUTCOME MEASURES Incidence rate ratios (IRRs) of strokes, thromboembolic events, cardiovascular deaths, and bleeding incidents by discontinuing warfarin as opposed to continued treatment 30 to 89 days, 90 to 179 days, 180 to 364 days, 365 to 729 days, and at least 730 days after surgery. RESULTS The median duration of follow-up was 6.57 person-years. Estimated rates of events per 100 person-years in patients not treated with warfarin compared with those treated with warfarin with comparative absolute risk were 7.00 (95% CI, 4.07-12.06) vs 2.69 (95% CI, 1.49-4.87; adjusted IRR, 2.46; 95% CI, 1.09-5.55) for strokes; 13.07 (95% CI, 8.76-19.50) vs 3.97 (95% CI, 2.43-6.48; adjusted IRR, 2.93; 95% CI, 1.54-5.55) for thromboembolic events; 11.86 (95% CI, 7.81-18.01) vs 5.37 (95% CI, 3.54-8.16; adjusted IRR, 2.32; 95% CI, 1.28-4.22) for bleeding incidents; and 31.74 (95% CI, 24.69-40.79) vs 3.83 (95% CI, 2.35-6.25; adjusted IRR, 7.61; 95% CI, 4.37-13.26) for cardiovascular deaths within 30 to 89 days after surgery; and 6.50 (95% CI, 4.67-9.06) vs 2.08 (95% CI, 0.99-4.36; adjusted IRR, 3.51; 95% CI, 1.54-8.03) for cardiovascular deaths within 90 to 179 days after surgery. CONCLUSION Discontinuation of warfarin treatment within 6 months after bioprosthetic AVR surgery was associated with increased cardiovascular death.

Association of β-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery: a Danish nationwide cohort study.

IMPORTANCE Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death). OBJECTIVE To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy. MAIN OUTCOMES AND MEASURES Thirty-day risk of MACE and all-cause mortality. RESULTS Of 28,263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20,273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years), with HRs of 0.54 (95% CI, 0.37-0.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P < .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score-matched analyses. CONCLUSIONS AND RELEVANCE Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.

Risk of Stroke After Coronary Artery Bypass Grafting: Effect of Age and Comorbidities

Background and Purpose— The risk of stroke after coronary artery bypass grafting (CABG) is known to increase dramatically with age. During recent years, the age of patients operated on has increased and concomitant therapy has changed. Therefore, we have re-evaluated the risk of stroke after CABG. Methods— Through the Danish National Hospital Register, we identified all 25 159 patients with isolated CABG from 1997 through 2006. Stroke, comorbidities, and medication were further obtained. Risk factors of stroke were determined through regression models. Results— Overall, 1901 patients (7.6%) suffered a stroke after surgery, 477 patients (2.0%) within 30 days after CABG. Rates of stroke per 100 person-years (95% CI) within 30 days after surgery increased with age: <60 years, 10.1 (7.8–13.0); 60 to 64 years, 18.4 (14.3–23.5); 65 to 69 years, 27.7 (23.0–33.3); 70 to 74 years, 36.0 (30.4–42.6); 75 to 79 years, 36.1 (29.1–44.7); ≥80 years, 38.0 (25.2–57.1). Risks of stroke within 30 days after surgery adjusted for age (reference: age <60 years), sex, relevant comorbidities, and selected medication included: 60 to 64 years: HR, 1.7 (P=0.005; 95% CI, 1.2–2.4), 65 to 69 years: HR, 2.4 (P=0.001; 95% CI, 1.7–3.3), 70 to 74 years: HR, 2.8 (P=0.001; 95% CI, 2.1–3.8), 75 to 79 years: HR, 2.8 (P=0.001; 95% CI, 2.0–4.0), ≥80 years: HR, 3.0 (P=0.001; 95% CI, 1.8–4.9), previous stroke: HR, 4.2 (P=0.001; 95% CI, 3.3–5.4), diabetes: HR, 1.3 (P=0.019; 95% CI, 1.1–1.7), hypertension: HR, 1.4 (P=0.003; 95% CI, 1.1–1.7), peripheral vascular disease: HR, 1.6 (P=0.001; 95% CI, 1.3–2.1), renal failure: HR, 1.7 (P=0.012; 95% CI, 1.1–2.5), statins: HR, 0.8 (P=0.049; 95% CI, 0.7–1.0), clopidogrel: HR, 0.6 (P=0.032; 95% CI, 0.4–1.0). Conclusions— The increase in stroke with age after CABG is moderate and the relation uncertain in ages older than 70 years. Declining CABG in elderly patients because of risk of stroke purely on the basis of high age is debatable.

Age-dependent trends in postoperative mortality and preoperative comorbidity in isolated coronary artery bypass surgery: a nationwide study.

OBJECTIVES An increasing number of octogenarians are being subjected to coronary artery bypass grafting (CABG). The purpose of this study was to examine age-dependent trends in postoperative mortality and preoperative comorbidity over time following CABG. METHODS All patients who underwent isolated CABG surgery between January 1996 and December 2012 in Denmark were included. Patients were identified through nationwide administrative registers. Age was categorized into five different groups and time into three periods to see if mortality and preoperative comorbidity had changed over time. Predictors of 30-day mortality were analysed in a multivariable Cox proportional-hazard models and survival at 1 and 5 years was estimated by Kaplan-Meier curves. RESULTS A total of 38 830 patients were included; the median age was 65.4 ± 9.5 years, increasing over time to 66.6 ± 9.5 years. Males comprised 80%. The number of octogenarians was 1488 (4%). The median survival was 14.7 years (60-69 years), 10.7 years (70-74 years), 8.9 years (75-79 years) and 7.2 years (≥80 years). The 30-day mortality rate was 3%, increasing with age (1% in patients <60 years, 8% in octogenarians). The long-term mortality rate at 1 and 5 years was 2 and 7% (age <60 years) and 14 and 36% (age >80 years), respectively. The proportion of patients >75 years increased from 10 to 20% during the study period as well as the proportion of patients undergoing urgent or emergency surgery. The burden of comorbidities increased over time, e.g. congestive heart failure 13-17%, diabetes 12-21%, stroke 9-11%, in all age groups. Age and emergency surgery were the main predictors of 30-day mortality: age >80 years [hazard ratio (HR): 5.75, 95% confidence interval (CI): 4.41-7.50], emergency surgery (HR: 5.23, 95% CI: 4.38-6.25). CONCLUSION Patients are getting older at the time of surgery and have a heavier burden of comorbidities than before. The proportion of patients undergoing urgent or emergency surgery increased with age and over time. Despite this, the 30-day mortality decreased over time and long-term survival increased, except in octogenarians where it was stable. Octogenarians had substantially higher 30-day mortality compared with younger patients but surgery can be performed with acceptable risks and good long-term outcomes.

Age-Specific Performance of the Revised Cardiac Risk Index for Predicting Cardiovascular Risk in Elective Noncardiac Surgery

Background— The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratification in noncardiac surgery. Its performance in unselected populations, including different age groups, has, however, not been systematically investigated. We assessed the relationship of RCRI with major adverse cardiovascular events in an unselected cohort of patients undergoing elective, noncardiac surgery overall and in different age groups. Methods and Results— We followed up all individuals ≥25 years who underwent major elective noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30-day risk of major adverse cardiovascular events (ischemic stroke, myocardial infarction, or cardiovascular death). There were 742 of 357 396 (0.2%), 755 of 74 889 (1.0%), 521 of 11 921 (4%), and 257 of 3146 (8%) major adverse cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence interval, 2.96–3.69), high-risk surgery 2.70 (2.46–2.96), congestive heart failure 2.65 (2.29–3.06), cerebrovascular disease 10.02 (9.08–11.05), insulin therapy 1.62 (1.37–1.93), and kidney disease 1.45 (1.33–1.59). Modeling RCRI classes as a continuous variable, C statistic was highest among age group 56 to 65 years (0.772) and lowest for those aged >85 years (0.683). Sensitivity of RCRI class >I (ie, having ≥1 risk factor) for capturing major adverse cardiovascular events was 59%, 71%, 64%, 66%, and 67% in patients aged ⩽55, 56 to 65, 66 to 75, 76 to 85, and >85 years, respectively; the negative predictive values were >98% across all age groups. Conclusions— In a nationwide unselected cohort, the performance of the RCRI was similar to that of the original cohort. Having ≥1 risk factor was of moderate sensitivity, but high negative predictive value for all ages.

Long-Term Prognostic Importance of Diabetes After a Myocardial Infarction Depends on Left Ventricular Systolic Function

OBJECTIVE This study was performed to understand how left ventricular function modulates the prognostic importance of diabetes after myocardial infarction (MI). RESEARCH DESIGN AND METHODS Consecutively hospitalized MI patients screened for three clinical trials were followed for a median of 7 years. Multivariable Cox regression models were used to assess the risk of mortality associated with diabetes, and the importance of diabetes was examined independently within defined left ventricular ejection fraction (LVEF) subgroups. RESULTS A total of 16,912 patients were included; 1,819 (11%) had diabetes. Diabetes and 15% unit depression in LVEF were of similar prognostic importance: hazard ratios (HRs) were 1.45 (95% CI 1.37–1.54) and 1.41 (1.37–1.45) for diabetes and LVEF depression, respectively. LVEF modified the outcomes associated with diabetes, with HRs being 1.29 (1.19–1.40) and 1.61 (1.49–1.74) in patients with LVEF <40% and LVEF ≥40%, respectively (P = 0.03). CONCLUSIONS Patients within the higher LVEF categories have a greater mortality risk attributable to diabetes than patients within the lower LVEF categories.

New-Onset Atrial Fibrillation Is a Predictor of Subsequent Hyperthyroidism: A Nationwide Cohort Study

Aims To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism. Methods and Results All patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done. Conclusion New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

Use of quinine and mortality-risk in patients with heart failure—a Danish nationwide observational study†

Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure.

Association of β-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery

IMPORTANCE Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death). OBJECTIVE To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy. MAIN OUTCOMES AND MEASURES Thirty-day risk of MACE and all-cause mortality. RESULTS Of 28,263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20,273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years), with HRs of 0.54 (95% CI, 0.37-0.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P < .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score-matched analyses. CONCLUSIONS AND RELEVANCE Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.

Risk of death and stroke associated with anticoagulation therapy after mitral valve repair

Objective Guidelines generally recommend oral anticoagulation to be considered the first 3 months after mitral valve repair based on small studies and consensus. However, in several studies no benefit of anticoagulation has been found. Methods From the national registries we identified all Danish patients who underwent mitral valve repair during the period between 1997 and 2012. Medication, hospitalisation and mortality data were studied. The association of use of vitamin K antagonists (VKAs) at discharge and risk of stroke/death was evaluated by means of Cox regression, landmark analyses and propensity matched models. Results 2188 patients without prior VKA use, stroke or death day 7 after discharge were included and median follow-up was 4.9 years (0–13.7). 859 (39%) were discharged on VKAs and 523 (24%) experienced death or stroke, 60 of these occurred within the first 3 months and 24 between 3 and 6 months. Compared with patients without post-discharge VKA, patients on VKA had a lower risk of death/stroke at 3 months (HR=0.28, CI (0.13 to 0.62), p=0.002) and in the time period from 3 to 6 months (HR=0.85, CI (0.35 to 2.07), p=0.72). Risk of significant bleeding complications within 3 months were comparable in the two groups with 23 (2%) among patients without VKA and 6 (1%) among VKA-treated. Conclusion VKA treatment after mitral valve repair is associated with a markedly lower risk of adverse events as stroke or death without excess major bleeding risk during the first 3 months following surgery.