Biomedical subjects

Douglas S Lee

Publications and source records attributed to Douglas S Lee.

At least 19 recordsLinked to original sources

PubMed2006

Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study.

OBJECTIVE: To determine whether serum gamma-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP). METHODS AND RESULTS: In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22). CONCLUSIONS: An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.

Adult↗

PubMed2006

Outcome of heart failure with preserved ejection fraction in a population-based study.

BACKGROUND: The importance of heart failure with preserved ejection fraction is increasingly recognized. We conducted a study to evaluate the epidemiologic features and outcomes of patients with heart failure with preserved ejection fraction and to compare the findings with those from patients who had heart failure with reduced ejection fraction. METHODS: From April 1, 1999, through March 31, 2001, we studied 2802 patients admitted to 103 hospitals in the province of Ontario, Canada, with a discharge diagnosis of heart failure whose ejection fraction had also been assessed. The patients were categorized in three groups: those with an ejection fraction of less than 40 percent (heart failure with reduced ejection fraction), those with an ejection fraction of 40 to 50 percent (heart failure with borderline ejection fraction), and those with an ejection fraction of more than 50 percent (heart failure with preserved ejection fraction). Two groups were studied in detail: those with an ejection fraction of less than 40 percent and those with an ejection fraction of more than 50 percent. The main outcome measures were death within one year and readmission to the hospital for heart failure. RESULTS: Thirty-one percent of the patients had an ejection fraction of more than 50 percent. Patients with heart failure with preserved ejection fraction were more likely to be older and female and to have a history of hypertension and atrial fibrillation. The presenting history and clinical examination findings were similar for the two groups. The unadjusted mortality rates for patients with an ejection fraction of more than 50 percent were not significantly different from those for patients with an ejection fraction of less than 40 percent at 30 days (5 percent vs. 7 percent, P=0.08) and at 1 year (22 percent vs. 26 percent, P=0.07); the adjusted one-year mortality rates were also not significantly different in the two groups (hazard ratio, 1.13; 95 percent confidence interval, 0.94 to 1.36; P=0.18). The rates of readmission for heart failure and of in-hospital complications did not differ between the two groups. CONCLUSIONS: Among patients presenting with new-onset heart failure, a substantial proportion had an ejection fraction of more than 50 percent. The survival of patients with heart failure with preserved ejection fraction was similar to that of patients with reduced ejection fraction.

Aged↗

PubMed2006

Association of parental heart failure with risk of heart failure in offspring.

BACKGROUND: The association between heart failure in parents and the prevalence of left ventricular systolic dysfunction and the risk of heart failure in their offspring has not been investigated in a community-based setting. METHODS: We examined the cross-sectional association of heart failure in parents with the prevalence of left ventricular systolic dysfunction, as well as left ventricular mass, internal dimensions, and wall thickness, in 1497 participants of the Framingham Offspring Study (mean age, 57 years; 819 women) who underwent routine echocardiography. We also investigated prospectively whether heart failure in parents increased the risk of heart failure in 2214 offspring (mean age, 44 years; 1150 women). RESULTS: As compared with the 1039 participants whose parents did not have heart failure, the 458 participants in the cross-sectional cohort who had at least one parent with heart failure were more likely to have increased left ventricular mass (17.0 percent vs. 26.9 percent), left ventricular internal dimensions (18.6 percent vs. 23.4 percent), and left ventricular systolic dysfunction (3.1 percent vs. 5.7 percent); the multivariable-adjusted odds ratios were 1.35 (95 percent confidence interval, 0.99 to 1.84), 1.29 (95 percent confidence interval, 0.96 to 1.72), and 2.37 (95 percent confidence interval, 1.22 to 4.61), respectively. In the longitudinal cohort, heart failure developed in 90 offspring during follow-up (mean length of follow-up, 20 years). The age- and sex-adjusted 10-year incidence rates of heart failure were 2.72 percent among offspring with a parent with heart failure, as compared with 1.62 percent among those without a parent with heart failure. This increase in risk persisted after multivariable adjustment (hazard ratio, 1.70; 95 percent confidence interval, 1.11 to 2.60). CONCLUSIONS: Heart failure in parents is associated with an increased prevalence of left ventricular systolic dysfunction cross-sectionally and an elevated risk of heart failure longitudinally. Our data emphasize the contribution of familial factors to the heart-failure burden in the community.

Adult Children↗

PubMed2006

Screening for ventricular remodeling.

Current guidelines emphasize the importance of preventing heart failure (HF) by targeting people with preclinical forms of the disease. Accordingly, there is considerable interest in identifying left ventricular (LV) remodeling, the fundamental substrate for HF, in asymptomatic individuals in the community. Increased LV mass and asymptomatic LV systolic and LV diastolic dysfunction are the remodeling phenotypes that could be potentially considered for population-wide screening. Plasma levels of natriuretic peptides (NP) have been extensively investigated for such screening purposes. However, a majority of investigations suggest that their performance characteristics are suboptimal for identifying LV remodeling phenotypes unless high-risk individuals (eg, older men with hypertension) are targeted. In general, the prevalence of LV systolic dysfunction in women is too low to justify screening. In recent reports, sequential screening strategies combining urine and plasma NP or plasma NP and hand-held portable echocardiography have been advocated as potential approaches to identify asymptomatic LV systolic dysfunction in a cost-effective manner. Additional studies are warranted to confirm these findings.

Biomarkers↗

PubMed2006

Goals and guidelines for treating hypertension in a patient with heart failure.

Hypertension promotes left ventricular (LV) hypertrophy and myocardial remodeling and is frequently present in patients with systolic or diastolic heart failure. Control of hypertension in both of these settings may attenuate progressive LV hypertrophy and remodeling and improve clinical outcomes. Guidelines for the management of heart failure recommend that hypertension should be treated in all patients with preclinical heart failure as well as in those with heart failure with reduced or preserved LV systolic function. Consistent with national hypertension guidelines, the goal for blood pressure control in hypertensive patients with heart failure is less than 140/90 mm Hg, but lower targets (< 130/80 mm Hg) may be desirable in those with concomitant diabetes mellitus or renal disease. Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and beta-adrenoreceptor antagonists are first-line options for hypertension treatment in heart failure. Calcium channel antagonists and the alpha blocker doxazosin should be avoided. Episodes of recurrent pulmonary edema and hypertension may also indicate underlying severe renovascular disease that may respond to percutaneous renal artery intervention.

Journal Article↗

PubMed2006

Do case-generic measures of queue performance for bypass surgery accurately reflect the waiting-list experiences of those most urgent?

BACKGROUND: Queue performance is typically assessed using generic measures, which capture the queue in aggregate. The objective of this study was to examine whether case-generic measures of queue performance appropriately reflected the waiting-list experiences of those patients with greatest disease severity. METHODS: We examined the queue for isolated coronary artery bypass grafting (CABG) in Ontario between April 1993 and March 2000 using data obtained from the Cardiac Care Network. Our primary measure of queue performance was the proportion of patients who received their bypass surgery within their recommended maximum waiting times (%RMWTs) in any given month. We compared case-generic measures of queue performance to case-specific measures of queue performance stratified by urgency level. RESULTS: The queue was largely comprised of elective cases ranging from 73% (1993) to 57%(1999). Urgent patients comprised the minority of the queue ranging from 14% (1993) to 20% (1999). Case-generic month-to-month variations in the percentage of cases completed within RMWTs (an aggregated waiting list measure encompassing the characteristics of all patients in the queue) closely resembled the experiences of elective patients (R2 = 0.81), but conversely, bore little relationship to the waiting-list experiences of those most urgent (R2 = 0.15). INTERPRETATION: Case-generic measures of queue performance for bypass surgery in Ontario were not reflective of the waiting-list experiences of those most urgent. Our results reinforce the concept that urgency-specific waiting list monitoring systems are required to best evaluate and appropriately respond to fluctuations in queue performance.

Coronary Artery Bypass↗

PubMed2005

Quality of care and outcomes of older patients with heart failure hospitalized in the United States and Canada.

BACKGROUND: Health care expenditure per person is significantly higher in the United States compared with Canada, but whether there are differences in quality of care of many conditions is unknown. We compared the process of care and outcomes of patients with heart failure, the most common cause of hospitalization for individuals 65 years and older in both countries. METHODS: We compared processes of care and 30-day and 1-year risk-standardized mortality rates among 28,521 US Medicare beneficiaries and 8180 similarly aged patients in Ontario, Canada, hospitalized with heart failure from 1998 to 2001. RESULTS: More US patients underwent left ventricular ejection fraction assessment during hospitalization compared with Canadian patients (61.2% vs 41.7%, P<.001). At discharge, patients in the United States were prescribed beta-blockers more frequently (28.7% vs 25.4%, P<.001) but angiotensin-converting enzyme inhibitors less frequently (54.3% vs 63.4%, P<.001). Among ideal candidates, prescription of beta-blockers (32.5% vs 29.7%, P = .08) or angiotensin-converting enzyme inhibitors (78.3% vs 77.6%, P = .68) was not significantly different between the 2 countries. The US patients had lower risk characteristics on admission and lower crude mortality rates at 30 days and 1 year. Thirty-day risk-standardized mortality was significantly lower for the US patients (8.9% vs 10.7%, P<.001), but 1-year risk-standardized mortality was no longer significantly different (32.2% vs 32.3%, P = .98). CONCLUSION: Patients with heart failure who are hospitalized in the United States had lower short-term mortality at 30 days, but 1-year mortality rates were not significantly different between the United States and Canada.

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PubMed2005

Risk-treatment mismatch in the pharmacotherapy of heart failure.

CONTEXT: Patients with heart failure have a wide spectrum of mortality risks. To maximize the benefit of available pharmacotherapies, patients with high mortality risk should receive high rates of drug therapy. OBJECTIVE: To examine patterns of drug therapy and underlying mortality risk in patients with heart failure. DESIGN, SETTING, AND PATIENTS: In the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) population-based cohort (1999-2001) of 9942 patients with heart failure hospitalized in Ontario, Canada, we evaluated 1418 patients with documented left ventricular ejection fraction of 40% or less and aged 79 years or younger with low-, average-, and high-predicted risk of death within 1 year; all patients survived to hospital discharge. Administration of angiotensin-converting enzyme (ACE) inhibitors, ACE inhibitors or angiotensin II receptor blockers (ARBs), and beta-adrenoreceptor antagonists was evaluated according to predicted risk of death. MAIN OUTCOME MEASURE: Heart failure drug administration rates at time of discharge and 90 days after hospital discharge. RESULTS: At hospital discharge, prescription rates for patients in the low-, average-, and high-risk groups were 81%, 73%, 60%, respectively, for ACE inhibitors; 86%, 80%, 65%, respectively, for ACE inhibitors or ARBs; and 40%, 33%, 24%, respectively, for beta-adrenoreceptor antagonists (all P<.001 for trend). Within 90 days following hospital discharge, the rates were 83%, 76%, and 61% for ACE inhibitors; 89%, 83%, and 67% for ACE inhibitors or ARBs; and 43%, 36%, and 28% for beta-adrenoreceptor antagonists for the 3 risk groups, respectively (all P<.001 for trend). The pattern of lower rates of drug administration in those patients at increasing risk was maintained up to 1 year postdischarge (P<.001). After accounting for varying survival time and potential contraindications to therapy, low-risk patients were more likely to receive ACE inhibitors or ARBs (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.49-1.74) and beta-adrenoreceptor antagonists (HR, 1.80; 95% CI, 1.60-2.01) compared with high-risk patients (both P<.001). CONCLUSIONS: Patients with heart failure at greatest risk of death are least likely to receive ACE inhibitors, ACE inhibitors or ARBs, and beta-adrenoreceptor antagonists. Understanding the reasons underlying this mismatch may facilitate improvements in care and outcomes for patients with heart failure.

Adrenergic beta-Antagonists↗

PubMed2005

How many patients with heart failure are eligible for cardiac resynchronization? Insights from two prospective cohorts.

AIMS: To determine what proportion of patients with heart failure are eligible for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Eligibility criteria from the trials establishing the efficacy of CRT were applied to two prospective cohorts: the first enrolled patients with newly diagnosed heart failure discharged from 103 hospitals between April 1999 and March 2001 ('the hospital discharge cohort'); the second enrolled patients seen in a specialized clinic between August 2003 and January 2004 ('the specialty clinic cohort'). In the hospital discharge cohort, 73 patients (3% of the 2640 patients with ischaemic or dilated cardiomyopathy and 1% of all 9096 patients with heart failure discharged alive) met trial eligibility criteria: LVEF< or =0.35, QRS > or =120 ms, sinus rhythm, and NYHA class III or IV symptoms despite the treatment with ACE-inhibitor/angiotensin receptor blocker and beta-blocker. In the specialty clinic cohort, 54 patients (21% of the 263 patients with ischaemic or dilated cardiomyopathy and 17% of all 309 patients with heart failure) met these criteria. If persistent symptoms despite taking spironolactone were required for CRT eligibility, then the proportions qualifying dropped to 1% in the hospital discharge cohort and 18% in the specialty clinic cohort. CONCLUSION: Few heart failure patients meet trial eligibility criteria for CRT.

Adrenergic beta-Antagonists↗

PubMed2005

Pharmacological treatment of congestive heart failure in Canada: a description of care in five provinces.

INTRODUCTION: Congestive heart failure (CHF) is responsible for significant morbidity, mortality and health resource consumption. There have been major advances in the treatment of this condition over the past two decades, yet little information is currently available regarding the current status of CHF management in Canada. OBJECTIVE: To describe the pharmacological management of patients hospitalized with CHF in five provinces: Alberta, British Columbia, Nova Scotia, Ontario and Quebec. DESIGN AND METHODS: Administrative data sources were used to identify all consecutive patients hospitalized with a principal diagnosis of CHF and discharged alive in the provinces of Alberta, British Columbia, Quebec and Ontario. Rates of use of prespecified medications at 30 days after hospital discharge were obtained for patients 65 years of age and older by linkage of their hospital records with drug benefit plans in these provinces. For Nova Scotia, the disease-specific registry of the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) study was used to obtain discharge medications of individuals consecutively hospitalized with a diagnosis of CHF. Where available, data were acquired from 1997 to 2002. RESULTS: Data were obtained for a total of 115,037 patients in the five provinces over the five-year period. Overall, 54.9% of patients received an angiotensin-converting enzyme inhibitor at or 30 days after hospital discharge, with minimal change in prescription rates over the five-year period. Beta-blocker prescription rates increased steadily during the study, more than doubling from 15.0% in 1997/1998 to 32.0% in 2001/2002. Spironolactone use increased dramatically, with only 2.2% of patients receiving this medication in 1997/1998 compared with 18.7% in 2001/2002. The rates of digoxin prescription decreased each year, while the use of angiotensin receptor blockers increased slightly throughout the observation period. CONCLUSIONS: While the use of evidence-based treatment for CHF in Canada is increasing and is currently at levels similar to those reported in other developed countries, there is still the potential in every province for further improvement.

Adrenergic beta-Antagonists↗

PubMed2005

Electrocardiographic prediction of the severity of posterior wall perfusion defects on rest technetium-99m Sestamibi myocardial perfusion imaging.

To identify electrocardiogram (ECG) variables predicting the severity of previous posterior wall myocardial infarction as measured by technetium-99m-Sestamibi rest single-photon emission computed tomography, we assessed agreement between ECG criteria and posterior wall perfusion defects (PWPDs) in 236 patients. Established ECG criteria for posterior and posterolateral infarctions were present in 22% and 19% of patients, respectively, and did not predict severity of PWPD ( P = NS). Univariate predictors of severity were the Selvester QRS score (SQS) ( P = .001) and an upright T wave in V 1 (UTV 1 ) greater than 0.2 mV ( P = .001). Regression analysis demonstrated that SQS ( P = .0001) and UTV 1 greater than 0.2 mV ( P = .006) were highly predictive of severity ( c statistic = 0.793). All severe PWPDs had an SQS of 2 or higher. Established ECG patterns for diagnosis of posterior infarction are insensitive and poor predictors of severity. The SQS and UTV 1 are effective for the diagnosis of posterior infarction and useful for the estimation of infarct severity.

Coronary Circulation↗

PubMed2005

Comparison of coding of heart failure and comorbidities in administrative and clinical data for use in outcomes research.

BACKGROUND: Despite the potential usefulness of administrative databases for evaluating outcomes, coding of heart failure and associated comorbidities have not been definitively compared with clinical data. OBJECTIVE: To compare the predictive value of heart failure diagnoses and secondary conditions identified in a large administrative database with chart-based records. METHODS: The authors studied 1808 patient records sampled from 14 acute care hospitals and compared clinically recorded data with administrative records from the Canadian Institute for Health Information. The impact of comorbidity coding in the administrative data set according to the Charlson classification was examined in models of 30-day mortality. RESULTS: The positive predictive value (PPV) of a primary diagnosis ICD-9 428 was 94.3% using the Framingham criteria and 88.6% using criteria previously validated with pulmonary capillary wedge pressure. There was reduced prevalence of secondary comorbid conditions in administrative data in comparison with clinical chart data. The specificities and PPV/negative predictive values of administratively identified index comorbidities were high. The sensitivities of index comorbidities were low, but were enhanced by examination of hospitalizations within 1 year prior to the index heart failure admission. Using information from prior hospitalizations modestly enhanced 30-day mortality model performance; however, the odds ratio point estimates of the index and enhanced administrative data sets were consistent with the clinical model. CONCLUSION: The ICD-9 428 primary diagnosis is highly predictive of heart failure using clinical criteria. Examination of hospitalization data up to 1 year prior to the index admission improves comorbidity detection and may provide enhancements to future studies of heart failure mortality.

Aged↗

PubMed2005

Novel markers for heart failure diagnosis and prognosis.

PURPOSE OF REVIEW: This paper reviews recent advances in heart failure biomarkers for identification of disease precursors, subclinical disease, and onset or progression of overt disease. RECENT FINDINGS: Heart failure biomarkers can be categorized empirically as neurohormonal mediators, markers of myocyte injury and remodeling, and indicators of systemic inflammation. Brain natriuretic peptide is the most widely studied, with a potentially important but evolving role for determining prognosis and as a surrogate endpoint in clinical trials. Strong evidence exists for use of brain natriuretic peptide in the diagnosis of acute heart failure and for improved clinical outcomes with a brain natriuretic peptide-guided approach to heart failure care. The use of brain natriuretic peptide as a screening tool for asymptomatic left ventricular systolic dysfunction, or to distinguish systolic from diastolic heart failure, is not supported by current data. Markers of myocyte injury, including troponins, heart-type fatty acid binding protein, and myosin light chain-1, may further improve heart failure prognostication in conjunction with plasma brain natriuretic peptide. Biomarkers of matrix remodeling and inflammation have emerged as potential preclinical indicators to identify individuals at risk of developing clinical heart failure. A role for cellular adhesion molecules may also emerge in identifying those at risk for cardiovascular thrombotic complications, such as stroke. SUMMARY: The spectrum of heart failure biomarkers and their potential clinical applications continues to grow. Ongoing research on multimarker strategies will likely identify biomarker combinations that are optimal at various stages during the evolution of heart failure, ranging from their use for screening, diagnosis, determining prognosis, and guiding management.

Biomarkers↗

PubMed2005

Potential gaps in congestive heart failure management in a rural hospital.

INTRODUCTION: Congestive heart failure (CHF) is increasingly recognized as an important cause of morbidity and mortality. Previous studies in urban settings have shown that patients frequently are not receiving recommended therapy. There is a paucity of studies that have evaluated CHF management in a rural setting. We therefore reviewed hospital and outpatient care in this setting as an initial step toward improving CHF care. METHOD: A retrospective chart review was used to examine the care of all 34 patients hospitalized for CHF from 2000-2001 in a small rural hospital, to assess the need for improved CHF management. RESULTS: The median age of the patients was 78 yr, and a number of them had many co-morbid cardiovascular risks. Similar to other studies, only 23% of patients were prescribed recommended doses of angiotensin-converting enzyme (ACE) inhibitors. Use of beta-blockers was far below expected rates. Although there was follow-up care for nearly all patients (97%), few patients had echocardiography performed (38%) or had their medications altered in the outpatient setting. CONCLUSION: There is a need for improved management of CHF in the rural setting. Approaches to improving CHF care should use the continuity of care advantage provided by primary care physicians to optimize outpatient medical treatment regimens and improve access to diagnostic services such as echocardiography.

Adult↗

PubMed2004

Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials.

Strategies to decrease sudden cardiac death in patients with left ventricular systolic dysfunction are evolving. Recent clinical trials have evaluated the role of prophylactic implantable cardioverter-defibrillators (ICDs) in patients with and without additional risk stratifiers. We pooled studies comparing treatment with and without ICDs from published data and presented abstracts, irrespective of QRS duration and etiology of systolic dysfunction. On the basis of the available clinical trials, implantation of an ICD for primary prevention of death provides a 7.9% absolute mortality reduction (p = 0.003) in patients with left ventricular (LV) systolic dysfunction who were receiving optimized medical therapy. This finding was not sensitive to the exclusion of any individual trial. The ICD is an effective primary preventative measure in patients who are at risk for death; however, the application of this therapy needs to be individualized for the patient, similar to drug therapies in LV systolic dysfunction. In health care settings without unlimited resources, optimal use of this therapy will require better risk stratification methods or lowering of the initial device cost.

Confounding Factors, Epidemiologic↗

PubMed2004

A systematic review and meta-analysis of studies comparing readmission rates and mortality rates in patients with heart failure.

BACKGROUND: Heart failure is the leading cause of hospitalization and readmission in many hospitals worldwide. We performed a meta-analysis to evaluate the effectiveness of multidisciplinary heart failure management programs on hospital admission rates. METHODS: We identified studies through an electronic search and mortality using 8 distinct methods. Eligible studies met the following criteria: (1) randomized controlled clinical trials of adult inpatients hospitalized for heart failure enrolled either at the time of discharge or within 1 week after discharge; (2) heart failure-specific patient education intervention coupled with a postdischarge follow-up assessment; and (3) unplanned readmission reported. Four reviewers independently assessed each study for eligibility and quality, achieving a weighted kappa of 0.73 for eligibility and 0.77 for quality. For each study we calculated the relative risk for readmissions and mortality for patients receiving enhanced education relative to patients receiving usual care. RESULTS: A total of 529 citation titles were identified, of which 8 randomized trials proved eligible. The pooled relative risk for hospital readmission rates using a random-effects model was 0.79 (95% confidence interval, 0.68-0.91; P<.001; heterogeneity P = .25). There was no apparent effect on mortality (relative risk, 0.98; 95% confidence interval, 0.72-1.34; P = .90; heterogeneity P = .20). Data were insufficient to meaningfully pool intervention effects on quality of life or compliance. CONCLUSION: This systematic review suggests that specific heart failure-targeted interventions significantly decrease hospital readmissions but do not affect mortality rates.

Aged↗

PubMed2004

Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.

BACKGROUND: The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together. METHODS: We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001. RESULTS: Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P<0.001). The rate of hospitalization for hyperkalemia rose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patients in 2001 (P<0.001), and the associated mortality rose from 0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As compared with expected numbers of events, there were 560 (95 percent confidence interval, 285 to 754) additional hyperkalemia-related hospitalizations and 73 (95 percent confidence interval, 27 to 120) additional hospital deaths during 2001 among older patients with heart failure who were treated with ACE inhibitors in Ontario. Publication of RALES was not associated with significant decreases in the rates of readmission for heart failure or death from all causes. CONCLUSIONS: The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication.

Adrenergic beta-Antagonists↗

PubMed2004

Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study.

BACKGROUND: Non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of congestive heart failure, but little is known about the cardiovascular effects of a newer group of NSAIDS called selective cyclo-oxygenase (COX)-2 inhibitors. We aimed to compare rates of admission for congestive heart failure in elderly patients who were newly dispensed COX-2 inhibitors or non-selective NSAIDs. METHODS: In this population-based retrospective cohort study we identified NSAID-naive individuals aged 66 years or older, who were started on rofecoxib (n=14,583), celecoxib (n=18,908), and non-selective NSAIDs (n=5,391), and randomly selected non-NSAID users as controls (n=100,000). FINDINGS: Relative to non-NSAID users, patients on rofecoxib and non-selective NSAIDS had an increased risk of admission for congestive heart failure (adjusted rate ratio 1.8, 95% CI 1.5-2.2, and 1.4, 1.0-1.9, respectively), but not celecoxib (1.0, 0.8-1.3). Compared with celecoxib users, admission was significantly more likely in users of non-selective NSAIDs (1.4, 1.0-1.9) and rofecoxib (1.8, 1.4-2.4). Risk of admission for rofecoxib users was higher than that for non-selective NSAID users (1.5, 1.1-2.1). Of patients with no admission in the past 3 years, only rofecoxib users were at increased risk of subsequent admission relative to controls (1.8, 1.4-2.3). INTERPRETATION: These findings suggest a higher risk of admission for congestive heart failure in users of rofecoxib and non-selective NSAIDs, but not celecoxib, relative to non-NSAID controls.

Aged↗