Amiodarone is associated with dysfunction of the thyroid. Concerns have arisen regarding the potential for adverse effects with generic formulations of amiodarone. We evaluated and compared the risk of thyroid dysfunction between patients using brand-name versus generic formulations of amiodarone and identified risk factors for thyroid dysfunction.
We conducted a retrospective cohort study of patients with atrial fibrillation aged 66 years and older. We used administrative databases that linked information on demographics and clinical characteristics, claims for prescription drugs and discharges from hospital. We estimated thyroid dysfunction using person-year incidence.
Of the 60,220 patients in the cohort, 2804 (4.7%) used the brand-name formulation of amiodarone and 6278 (10.4%) used the generic formulation. Baseline characteristics between these two groups were comparable. The median maintenance dose of amiodarone was 200 mg/d for both groups. The total incidence rate for thyroid dysfunction was 14.1 per 100 person-years for both formulations. The mean time to clinical dysfunction of the thyroid was 4.32 years for the brand-name formulation and 4.09 years for the generic formulation. In a multivariate analysis, there was no significant difference in the incidence rates of thyroid dysfunction between the generic and brand formulations (hazard ratio 0.97, 95% confidence interval 0.87-1.08). Factors associated with an increased risk of thyroid dysfunction were being a woman, increasing age and having chronic obstructive pulmonary disease.
In this population-based study, we saw no difference between brand-name and generic formulations of amiodarone in terms of incidence of thyroid dysfunction.
Several randomized controlled trials demonstrate that angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF). However, whether ACE inhibitors benefit both sexes is not adequately addressed.
Our objective was to determine the effectiveness of ACE inhibitors in women with CHF.
The Quebec hospital discharge database was linked with the physician and drug claims database to identify a cohort with a discharge diagnosis of CHF between January 1998 and March 2003. In this retrospective cohort study, subjects who filled a prescription for ACE inhibitors (19,220 exposed) were compared to those who never filled such prescription (8617 non-exposed). The primary outcome was survival by exposure to ACE inhibitors.
There were 14,693 women (67% exposed) and 13,144 men (72% exposed). The 1 year mortality was 19.5% and 30% in those exposed and non-exposed, respectively. A significant survival benefit was demonstrated in both sexes exposed to ACE inhibitors [adjusted hazard ratio (95% confidence interval): women 0.80 (0.76-0.85); men 0.71 (0.67-0.75)].
ACE inhibitors improve survival in both sexes with CHF, but the protective effect appears to be greater in men. Our results support the current recommendations for the management of women with CHF.
To examine the class effect of angiotensin II receptor blockers (ARBs) on mortality in patients with heart failure who were aged 65 years or older.
Retrospective population-based study.
Administrative database that stores information on hospital discharge summaries for the Canadian provinces of Quebec, Ontario, and British Columbia.
A total of 6876 patients aged 65 years or older who were discharged with a primary diagnosis of heart failure between January 1, 1998, and March 31, 2003, and who filled at least one prescription for an ARB within 90 days of discharge.
Times to all-cause death in patients receiving individual ARBs were compared. Models were adjusted for demographic, clinical, physician, and hospital characteristics; models were also adjusted for dosage categories, which were represented by time-dependent variables. The cohort of 6876 patients had a mean +/- SD age of 78 +/- 7 years, and most (62%) were women. Losartan was the most frequently prescribed ARB (61%), followed by irbesartan (14%), valsartan (13%), candesartan (10%), and telmisartan (2%). Irbesartan, valsartan, and candesartan were associated with better survival rates than losartan (adjusted hazard ratios [HRs] and 95% confidence intervals [CIs] 0.65 [0.53-0.79], 0.63 [0.51-0.79], and 0.71 [0.57-0.90], respectively). No difference was noted in mortality in patients prescribed telmisartan compared with those receiving losartan (HR 0.92 [95% CI 0.55-1.54]).
Elderly patients with heart failure who were prescribed losartan had worse survival rates compared with those prescribed other commonly used ARBs. The absence of a class effect for ARBs is consistent with data showing pharmacologic differences among the drugs.
Clinical studies have shown the benefit of statin use after acute myocardial infarction (AMI). However, it is uncertain how this benefit relates to the timing of statin initiation after AMI. We created a retrospective cohort (from 1996 to 2001) using health care databases in Quebec, Canada, to study patients (> or =65 years of age) who had AMI and differed in time of statin initiation within the first 90 days after discharge. Rates of recurrent AMI and mortality were compared between patients who initiated statins at discharge (early group) and those who initiated statins 1 month later and up to 90 days after discharge (delayed group). A multivariate Cox's regression model was used in the comparison. We used prescription time distribution matching to control for survival difference between groups. The early and delayed groups consisted of 3,075 and 1,187 patients, respectively. During the 1-year follow-up, there was no evidence to suggest a difference in outcome between groups. Adjusted hazard ratios for early versus delayed initiation were 1.03 (95% confidence interval 0.56 to 1.87) at 3 months and 1.24 (95% confidence interval 0.96 to 1.62) at 1 year. Analyses that were restricted to first-time statin users or excluded patients who had severe co-morbidity or were > or =85 years old did not change the results. Our findings were not affected by changing the definition of delayed use within the 90-day period. In conclusion, delay of statin initiation up to 30 to 90 days after discharge after AMI does not appear to lead to a difference in the rates of recurrent AMI and mortality compared with statin initiation at discharge.
Geographical variations in the use of invasive cardiac procedures have been documented. It remains unclear to what extent these variations exist across the Canadian provinces.
To describe variation in the use of invasive cardiac procedures and waiting times for these procedures across nine Canadian provinces.
Using longitudinal, de-identified patient data from the Canadian Institute for Health Information, records of patients who had suffered an acute myocardial infarction (AMI) in each of nine Canadian provinces between 1997/1998 and 1999/2000 were selected. Rates and median waiting times for percutaneous coronary intervention and coronary artery bypass graft surgery were calculated by age, sex and health region.
There was a large variation in the use of and waiting times for invasive cardiac procedures across the Canadian provinces studied. In general, cardiac procedure rates in Western provinces were higher than in Eastern provinces, most notably higher than in the Maritime provinces and Ontario. In addition to interprovincial variation, there was also significant regional variation in the rates of revascularization and waiting times. Rates of percutaneous coronary intervention increased over the study period, whereas rates of bypass surgery remained relatively stable.
Significant variation in the use of cardiac procedures after AMI exists across Canada and this April represent potential inequalities in the treatment of AMI across Canada.
Studies from the early 1990s have documented greater intensity of treatment for patients with acute myocardial infarction (AMI) in the United States compared with Canada, with little difference in health outcomes. Little is known about whether treatments and outcomes are changing differently over time in the two countries, and whether the differences vary with patient age.
We conducted a retrospective cohort study of trends in cardiac procedure use, mortality, and recurrent AMI for patients 65 years or older hospitalized with AMI in the United States and Quebec. We examined Medicare claims and enrollment data from the United States (1.5 million) and provincial claims data from Quebec (35,000) between 1988 and 1994.
Use of cardiac procedures grew more rapidly between 1988 and 1994 in the United States, particularly for patients 75 years or older; unlike in Quebec, these cardiac procedures were performed soon after AMI. Both countries experienced significant declines in 1-year mortality: the decline averaged 1.27% points per year in the United States and 1.05% points in Quebec (P = ns). For AMI patients 75 years or older, 30-day and 1-year mortality declined approximately twice as rapidly in the United States as in Quebec (P
This study sought to characterize temporal trends in all-cause mortality in patients with congenital heart disease (CHD).
Historically, most deaths in patients with CHD occurred in early childhood. Notable advances have since been achieved that may impact on mortality trends.
We conducted a population-based cohort study of patients with CHD in Quebec, Canada, from July 1987 to June 2005. A total of 8,561 deaths occurred in 71,686 patients with CHD followed for 982,363 patient-years.
The proportion of infant and childhood deaths markedly declined from 1987 to 2005, with a reduction in mortality that exceeded that of the general population. Distribution of age at death transitioned from a bimodal to unimodal, albeit skewed, pattern, more closely approximating the general population. Overall, mortality decreased by 31% (mortality rate ratio: 0.69, 95% confidence interval [CI]: 0.61 to 0.79) in the last (2002 to 2005) relative to the first (1987 to 1990) period of observation. Mortality rates decreased in all age groups below 65 years, with the largest reduction in infants (mortality rate ratio: 0.23, 95% CI: 0.12 to 0.47). In adults 18 to 64 years, the mortality reduction (mortality rate ratio: 0.84, 95% CI: 0.73 to 0.97) paralleled the general population. Gains in survival were mostly driven by reduced mortality in severe forms of CHD, particularly in children (mortality rate ratio: 0.33, 95% CI: 0.19 to 0.60), and were consistent across most subtypes.
Deaths in CHD have shifted away from infants and towards adults, with a steady increase in age at death and decreasing mortality.
Aortic coarctation (CoA) is reported to predispose to coronary artery disease (CAD). However, our clinical observations do not support this premise. Our objectives were to describe the prevalence of CAD among adults with CoA and to determine whether CoA is an independent predictor of CAD or premature CAD.
The study population was derived from the Quebec Congenital Heart Disease Database. We compared patients with CoA and those with a ventricular septal defect, who are not known to be at increased risk of CAD. The prevalence of CAD in patients with CoA compared with those with ventricular septal defect was determined. We then used a nested case-control design to determine whether CoA independently predicted for the development of CAD. Of 756 patients with CoA who were alive in 2005, 37 had a history of CAD compared with 224 of 6481 patients with ventricular septal defect (4.9% versus 3.5%; P=0.04). Male sex (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.62-2.80), hypertension (OR, 1.95; 95% CI, 1.44-2.64), diabetes mellitus (OR, 1.68; 95% CI, 1.09-2.58), age (OR per 10-year increase, 2.28; 95% CI, 2.09-2.48), and hyperlipidemia (OR, 11.58; 95% CI, 5.75-23.3) all independently predicted for the development of CAD. CoA did not independently predict for the development of CAD (OR, 1.04; 95% CI, 0.68-1.57) or premature CAD (OR for CoA versus ventricular septal defect, 1.44; 95% CI, 0.79-2.64) after adjustment for other factors.
Although traditional cardiovascular risk factors independently predicted for the development of CAD, the diagnosis of CoA alone did not. Our findings suggest that cardiovascular outcomes of these patients may be improved with tight risk factor control.
Controversy continues concerning the choice of rhythm control vs rate control treatment strategies for atrial fibrillation (AF). A recent clinical trial showed no difference in 5-year mortality between the 2 treatments. We aimed to determine whether the 2 strategies have similar effectiveness when applied to a general population of patients with AF with longer follow-up.
We used population-based administrative databases from Quebec, Canada, from 1999 to 2007 to select patients 66 years or older hospitalized with an AF diagnosis who did not have AF-related drug prescriptions in the year before the admission but received a prescription within 7 days of discharge. Patients were followed until death or administrative censoring. Mortality was analyzed by multivariable Cox regression.
Among 26,130 patients followed for a mean (SD) period of 3.1 years (2.3 years), there were 13,237 deaths (49.5%). After adjusting for covariates, we found that the effect of rhythm vs rate control drugs changed over time: after a small increase in mortality for patients treated with rhythm control in the 6 months following treatment initiation (hazard ratio [HR], 1.07; 95% CI, 1.01-1.14), the mortality was similar between the 2 groups until year 4 but decreased steadily in the rhythm control group after year 5 (HR, 0.89; 95% CI, 0.81-0.96; and HR, 0.77; 95% CI, 0.62-0.95, after 5 and 8 years, respectively).
In this population-based sample of patients with AF, we found little difference in mortality within 4 years of treatment initiation between patients with AF initiating rhythm control therapy vs those initiating rate control therapy. However, rhythm control therapy seems to be superior in the long-term.
Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada; Division of Cardiology, Department of Medicine, Jewish General Hospital, Montreal, Quebec, Canada; Division of Clinical Epidemiology, Department of Medicine, Jewish General Hospital, Montreal, Quebec, Canada.
Patients with cardiovascular disease are increasingly exposed to low-dose ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous studies have suggested that the malignancy risk associated with LDIR may be greatest in women and in young patients. We sought to compare the effect of LDIR on incident cancer across gender and age strata in a population-based cohort of patients with myocardial infarction (MI). All initially cancer-free patients with MI from 1996 to 2006 were identified in a province-wide administrative database. Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac LDIR exposure variable. Time-dependent multivariate Cox regression was used to determine the relation between cardiac LDIR and incident cancer. A time-lag covariate of 3 years was used wherein a de novo cancer could only be attributed to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR-associated risk of cancer was evaluated with stratified models and the addition of interaction terms. The study cohort consisted of 56,606 men and 26,255 women. For each millisievert of cardiac LDIR, women were more likely to develop a cancer (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age, noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the range studied (predominantly patients aged >50 years), age was not a determinant of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from cardiac imaging and therapeutic procedures after MI are at a greater risk of incident cancer compared with men after similar exposure. The extrapolated absolute risk from LDIR exposure would nonetheless be expected to be low.