Biomedical subjects

David H Fitchett

Publications and source records attributed to David H Fitchett.

9 recordsLinked to original sources

PubMed2006

Age-related differences in the management and outcome of patients with acute coronary syndromes.

BACKGROUND: Age-related differences in patients with an acute coronary syndrome (ACS) have not been well characterized in prior observational studies that often included only certain age groups or subjects with myocardial infarction (MI). METHODS: We stratified 4627 patients admitted with an ACS across 9 provinces between 1999 and 2001 enrolled in the Canadian ACS Registry into 3 age groups (< 65, 65-74, and > or = 75 years) to evaluate differences in clinical characteristics, management, and 1-year outcome. RESULTS: Older patients more frequently had previous angina, MI, or heart failure and were less likely to have positive cardiac markers, ST elevation, and Q-wave MI or to receive thrombolytics, beta-blockers, and cholesterol-lowering and antiplatelet agents in hospital, at discharge, and at 1 year. In multivariable analyses controlling for patient factors, every decade increase in age was independently associated with reduced use of coronary angiography (odds ratio [OR] 0.79, 95% CI 0.74-0.84, P < .001) and percutaneous coronary intervention (OR 0.88, 95% CI 0.81-0.95, P = .001). When adjusted for validated clinical prognosticators and differences in management, every decade of age increment independently predicted an increased risk of death at 1 year (OR 1.87, 95% CI 1.66-2.12, P < .001). CONCLUSIONS: Across the broad spectrum of ACS, elderly patients had more complex comorbidities and worse outcome, yet they were less likely to undergo revascularization or to receive acute and long-term evidence-based medications. Our findings emphasize the ongoing need to better define and promote optimal therapeutic regimens for elderly patients with ACS.

Age Factors↗

PubMed2006

Randomized evaluation of the efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Long-term results of the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial.

BACKGROUND: Patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) benefit from the early administration of aspirin, a small molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin and eptifibatide, the use of enoxaparin compared with unfractionated heparin (UFH) was associated with less bleeding, less early myocardial ischemia, and improved 30-day outcomes. OBJECTIVE: The aim of our study was to determine whether the short-term benefits of enoxaparin compared with UFH observed in high-risk patients with NSTE ACS are maintained over a prolonged period of follow-up. METHODS: Six hundred thirty-nine patients that were representative of the total population of subjects in the INTERACT trial were followed up for a median period of 2.5 years. RESULTS: In this group, the early benefit of enoxaparin was maintained. The incidence of death or myocardial infarction at the time of long-term follow-up was 39% lower in patients receiving enoxaparin compared with those who received UFH (8.9% vs 14.7%, P = .024). There was no difference in the frequency of cardiac catheterization in the groups receiving either enoxaparin or UFH. CONCLUSIONS: The early treatment of high-risk patients with NSTE ACS receiving aspirin and eptifibatide with enoxaparin is associated with early outcome benefits that are sustained over a prolonged follow-up period. This trial supports the concept that early treatment directed against platelet and thrombin formation is associated with better short- and long-term outcomes.

Angina, Unstable↗

PubMed2006

ST-segment depression in non-ST elevation acute coronary syndromes: quantitative analysis may not provide incremental prognostic value beyond comprehensive risk stratification.

BACKGROUND: It is unclear whether quantitative ST-segment assessment can improve risk stratification of unselected acute coronary syndrome (ACS) patients using the validated Global Registry of Acute Cardiac Events (GRACE) risk model. METHODS: In the prospective, multicenter, Canadian ACS Registry, the admission electrocardiogram was evaluated centrally at a blinded core laboratory. Patients with ST-elevation myocardial infarction and other electrocardiogram confounders were excluded. ST depression (ST down) was measured and summed in all leads except aVR. Patients with ST down were divided into 3 groups based on tertiles of cumulative ST down. A multivariable model was developed to examine the independent prognostic value of ST down severity after adjusting for other known prognosticators in the GRACE risk model. RESULTS: Among 2590 patients with non-ST-elevation ACS, more severe ST down was associated with advanced age, higher heart rate and Killip class, elevated creatinine, abnormal biomarkers, higher GRACE risk score, and higher 1-year mortality (all P < .001). After adjusting for these confounding prognosticators, the presence of any ST down remained independently associated with higher 1-year mortality (odds ratio 1.78, 95% CI 1.21-2.63, P = .004). However, the gradient of risk with increasing magnitude of ST down was no longer evident (adjusted odds ratios 1.77, 1.77, 1.81, for ascending tertiles of cumulative ST down, respectively). Moreover, quantitative ST down did not improve the model discrimination for 1-year mortality. The results were similar when the number of leads with ST down or the maximum magnitude of ST down was analyzed, after adjusting for tertiles of GRACE risk score or inhospital revascularization, or using the composite end point of death or myocardial (re)infarction at 1 year. CONCLUSIONS: Greater ST down is associated with other adverse prognosticators across the broad spectrum of non-ST-elevation ACS. Although the presence of any ST down is an independent predictor of 1-year mortality, its quantitative assessment is not as important as its mere presence when studied on the background of comprehensive clinical and biomarker evaluation in a nonclinical trial-based ACS population.

Aged↗

PubMed2006

Underuse of evidence-based treatment partly explains the worse clinical outcome in diabetic patients with acute coronary syndromes.

BACKGROUND: Diabetes-related differences in treatment and clinical outcome of patients across the entire spectrum of acute coronary syndromes (ACSs) have potential clinical implications but have not been well studied. METHODS: The multicenter, prospective, Canadian ACS Registry enrolled 4578 patients hospitalized for ACS between 1999 and 2001 across 9 provinces in Canada. We compared baseline characteristics, in-hospital and post-discharge treatments, and clinical outcome of diabetic and non-diabetic patients. The impact of diabetes on use of thrombolytic therapy and coronary revascularization; and the independent association between diabetes, treatments, and diabetes-treatment interactions on outcome were examined. RESULTS: Diabetic patients with ACS had more cardiovascular risk factors and higher-risk clinical presentation. They paradoxically received less evidence-based medications in-hospital, at discharge, and at 1-year. Although diabetes independently predicted higher 1-year mortality (OR 1.47, 95% CI 1.15-1.87; P = .002) after adjustment for validated prognosticators, it was also an independent predictor of not receiving thrombolytic therapy (OR 0.72, 95% CI 0.54-0.95; P = .021) and coronary revascularization (OR 0.69, 95% CI 0.59-0.82; P < .001). These underused therapies were all independently associated with reduced 1-year mortality, with no significant diabetes-related treatment-outcome heterogeneity. Importantly, diabetes remained an independent adverse prognosticator even after further adjustment for these differences in treatment. CONCLUSIONS: Evidence-based therapies are underused in the contemporary management of diabetic patients with ACS, which partly explains their worse outcome. Diabetes should be considered a high-risk feature in ACS risk stratification that encourages more intensive treatments. Continued efforts to promote adherence to existing proven therapies and to develop novel treatment strategies targeting diabetes-specific cardiovascular pathophysiology are imperative to improve their adverse prognosis.

Acute Disease↗

PubMed2006

Contemporary management of dyslipidemia in high-risk patients: targets still not met.

PURPOSE: Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients. METHODS: Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol<2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70 mg/dL]) for very high-risk patients. RESULTS: Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD (P<.0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P<.0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P<.0001). CONCLUSION: Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.

Aged↗

PubMed2006

Lower is better: implications of the Treating to New Targets (TNT) study for Canadian patients.

Recent clinical trials have indicated that lowering low-density lipoprotein cholesterol (LDL-C) levels below currently recommended targets results in favourable surrogate and clinical end points. The Treating to New Targets (TNT) study now confirms that aggressive cholesterol lowering to a mean LDL-C of 2.0 mmol/L with atorvastatin 80 mg daily, compared with the previous target of 2.5 mmol/L with atorvastatin 10 mg daily, results in improved clinical outcomes in high-risk patients with coronary artery disease. A lower LDL-C target of less than 2.0 mmol/L will present therapeutic challenges, because approximately only one-half of high-risk patients will achieve this target using monotherapy with the newer and more powerful statins. Furthermore, registry data show that one-half of these patients are not even achieving the current LDL-C target of 2.5 mmol/L. Causes of the care gap are discussed and possible remedies to achieve the new lower targets are suggested.

Atorvastatin↗

PubMed2006

Non ST segment elevation acute coronary syndromes: A simplified risk-orientated algorithm.

Non-ST segment elevation acute coronary syndromes (NSTE ACS) include a clinical spectrum that ranges from unstable angina to NSTE myocardial infarction. Management goals aim to prevent recurrent ACS and improve long-term outcomes by choosing a treatment strategy according to an estimate of the risk of an adverse outcome. Recent registry data suggest that patients with NSTE ACS frequently do not receive recommended treatment, and that risk stratification is not used to determine either the choice of treatment or the speed of access to coronary angiography. The present article evaluates the evidence for recommended treatment using information from recent trials and guidelines published by the major cardiac organizations in Europe and North America. Using this information, a multidisciplinary group developed a simplified algorithm that uses risk stratification to select an optimal early management strategy. Long-term outcomes are improved by a multi-faceted vascular protection strategy that is initiated at the time of hospitalization for NSTE ACS.

Acute Disease↗

PubMed2006

Bedtime administration of graded-release diltiazem in patients with inadequate BP control: a tolerability and efficacy study.

BACKGROUND: Achievement of target BP is a challenge in patients attending family practice. The long duration between administration of the last bedtime dose of antihypertensive medication and the physiologic early morning surge in BP makes it difficult to achieve satisfactory BP control. OBJECTIVE: To determine whether a new graded-release preparation of diltiazem (diltiazem XC), taken once daily at bedtime, will show an acceptable adverse-effect profile as well as improved BP control. STUDY DESIGN/SETTING: This is an open label, observational study in an ambulatory care setting. PATIENTS: 954 patients with mild to moderate hypertension and BP not at target levels were attended by 85 physicians. Group 1 patients were receiving a diltiazem preparation and group 2 patients were not receiving any diltiazem preparation at baseline. INTERVENTION: Group 1 patients were given diltiazem XC at the same dose as the prestudy diltiazem. Treatment with diltiazem XC 180 mg was initiated in group 2 patients. Diltiazem XC was taken once daily at bedtime in both groups. MAIN OUTCOME MEASURE: The predetermined main outcome measure was the development of adverse events with diltiazem XC when changing or adding the study medication. The secondary outcome measure was the proportion of patients who achieved target BP levels. RESULTS: Moderate or severe adverse events occurred in 8.7% of patients. Although 21.8% of patients reported either new or worsening adverse events after starting diltiazem XC, the large majority of adverse events were mild in severity. The most frequent moderate or severe adverse events were headache (2.0%) and constipation (1.7%). More patients in group 2 reported adverse events compared with patients in group 1. Target BP levels were achieved in 47.8% (95% CI 44.3, 51.3) of patients completing the 8- to 12-week treatment. No difference was found in the proportion of patients at target BP levels in groups 1 and 2. CONCLUSION: Diltiazem XC, when used in an ambulatory care setting for patients who have not achieved BP targets, shows an acceptable adverse-effect profile and results in an important improvement of BP control.

Aged↗

PubMed2005

Are Canadian guidelines for cholesterol lowering in high-risk patients optimal?

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.

Atorvastatin↗