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Biomedical subjects

Daniel G Hackam

Publications and source records attributed to Daniel G Hackam.

At least 19 recordsLinked to original sources
PubMed2006

Antithrombotic treatment for peripheral arterial disease.

CONTEXT: Patients with peripheral arterial disease (PAD) bear a substantial risk for vascular events in the coronary, cerebral and peripheral circulations. In addition, this disorder is associated with a systemic milieu characterised by ongoing platelet activation and heightened thrombogenesis. OBJECTIVE: To determine the optimal antithrombotic prophylaxis for patients with PAD. DATA SOURCES: Using terms related to PAD and antithrombotic agents, we searched the following databases for relevant articles: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the National Institutes of Health Clinical Trials Database, Web of Science, and the International Pharmaceutical Abstracts Database (search dates: 1 January 1990 to 1 January 2007). Additional articles were identified from cardiovascular and vascular surgery conference proceedings, bibliographies of review articles, and personal files. STUDY SELECTION: We focused on randomised trials, systematic reviews and consensus guidelines of antithrombotic therapies for PAD. DATA EXTRACTION: Detailed study information was abstracted by each author working independently. RESULTS: Multiple studies show that patients with PAD manifest platelet hyperaggregability, increased levels of soluble platelet activation markers, enhanced thrombin generation and altered fibrinolytic potential. Many of these markers predict subsequent cardiovascular events. Available randomised trials and meta-analyses show that most available antithrombotic agents prevent major cardiovascular events and death in patients with PAD, including aspirin, aspirin/dipyridamole, clopidogrel, ticlopidine, picotamide and oral anticoagulants. CONCLUSIONS: Although the most favourable risk-benefit profile, cost-effectiveness and overall evidence base supports aspirin in this setting, we provide scenarios in which alternatives to aspirin should be considered.

Anticoagulants↗
PubMed2006

Supporting a call to action for peripheral artery disease: insights from two prospective clinical registries.

BACKGROUND: Patients affected by peripheral arterial disease (PAD) incur a heightened risk of adverse cardiovascular events, including stroke, myocardial infarction, and vascular mortality. We examined risk factors, medications, and prognosis of outpatients with PAD enrolled in two national, prospective, practice-based Canadian registries that encompassed 484 physician practices: the Vascular Protection and Guideline Oriented Approach in Lipid Lowering registries. METHODS: The 2 registries were combined to analyze 9810 patients with vascular disease, diabetes mellitus, or age 65 years or older plus at least 2 additional cardiovascular risk factors. Risk factors, medications, and major cardiovascular events were recorded at baseline and again at 6 months' follow-up. RESULTS: Compared with patients without PAD (n = 8303), those with PAD (n = 1507) had substantially worse risk factor profiles and were more likely to have coexisting coronary or cerebrovascular disease. Both groups received high rates of treatment with evidence-based therapies, including antiplatelet drugs, statins, and angiotensin-converting enzyme inhibitors. Despite this, patients with PAD had a nearly twofold higher risk of major cardiovascular events at 6 months than non-PAD patients (7.3% vs 4.1%; P < .0001). After adjustment for multiple confounding factors, the presence of PAD at baseline continued to predict a heightened risk of adverse vascular sequelae (odds ratio, 1.54; 95% confidence interval, 1.18-2.01; P < .0001). CONCLUSIONS: These data support a strong relationship between PAD and worsened vascular prognosis that is independent of both conventional vascular risk factors and concomitant cardiovascular disease. The presence of PAD should therefore provide a clear impetus for intensive risk factor modification and use of preventive medical therapy in affected patients.

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PubMed2006

Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS: We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS: Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION: ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

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PubMed2006

Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis.

BACKGROUND: Atherosclerosis and sepsis share several pathophysiological similarities, including immune dysregulation, increased thrombogenesis, and systemic inflammation. The relation between statins and risk of sepsis in patients with atherosclerosis is unknown. METHODS: We did a population-based cohort analysis through linked administrative databases in Ontario, Canada, with accrual from 1997 to 2002. We identified 141,487 patients older than 65 years who had been hospitalised for an acute coronary syndrome, ischaemic stroke, or revascularisation, who survived for at least 3 months after discharge. 46,662 (33%) were prescribed a statin within 90 days of discharge, 94,825 (67%) were not. Propensity-based matching, which accounted for each individual's likelihood of receiving a statin, yielded a cohort of 69,168 patients, of whom half (34,584) received a statin and half (34,584) did not. FINDINGS: Incidence of sepsis was lower in patients receiving statins than in controls (71.2 vs 88.0 events per 10,000 person-years; hazard ratio [HR] 0.81; 95% CI 0.72-0.91). Adjustment for demographic characteristics, sepsis risk factors, comorbidities, and health-care use gave similar results (HR 0.81; 95% CI 0.72-0.90). The protective association between statins and sepsis persisted in high-risk subgroups, including patients with diabetes mellitus, chronic renal failure, or a history of infections. Significant reductions in severe sepsis (HR 0.83; 95% CI 0.70-0.97) and fatal sepsis (0.75; 0.61-0.93) were also observed. No benefit was noted with non-statin lipid-lowering agents (0.95; 0.75-1.22). IMPLICATIONS: Use of statins in patients with atherosclerosis is associated with a reduced risk of subsequent sepsis. Randomised trials of statins for prevention of sepsis are warranted.

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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.

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PubMed2006

Perioperative beta-blocker therapy in vascular surgery: clinical update.

Patients undergoing vascular surgery comprise a group at elevated risk of fatal and nonfatal perioperative cardiovascular events. In four recent longitudinal studies, the 30-day incidence of death in such patients was 3% to 6%, and the incidence of myocardial infarction was 5% to 14%. Growing evidence suggests that beta-adrenergic receptor antagonists prevent cardiovascular morbidity and mortality in high-risk patients undergoing noncardiac surgery, including those undergoing vascular surgery. This article reviews the available evidence concerning beta-blockers and provides guidance for their use in the perioperative setting.

Adrenergic beta-Antagonists↗
PubMed2006

Statins: panacea for sepsis?

Sepsis occurs when the immune system responds to a localised infection at a systemic level, thereby causing tissue damage and organ dysfunction. Statins have proven health benefits in many diseases involving vascular inflammation and injury. Recent animal data suggest that the administration of a statin before a sepsis-inducing insult reduces morbidity and improves survival. The immunomodulatory and anti-inflammatory effects of statins, collectively referred to as pleiotropic effects, lend biological plausibility to such findings. Limited human data hint at reduced mortality rates in bacteraemic patients, and a reduced risk of sepsis in patients with bacterial infections concurrently taking statins. These lines of evidence point to a potential new treatment and prevention modality for sepsis. The stage is set for randomised controlled clinical trials that will determine whether statins represent a safe and beneficial treatment in critically ill, septic patients and whether statins are effective at preventing sepsis in high-risk clinical settings.

Animals↗
PubMed2006

Intensive reduction of low-density lipoprotein-cholesterol: implications of recent trials.

Strong evidence supports the use of HMG-CoA reductase inhibitors (statins) for preventing ischemic events in a variety of clinical settings. Benefits have been documented in primary and secondary prevention, across a range of baseline cholesterol levels, in the young and old, and in patients with varying manifestations of cardiovascular disease. Epidemiologic evidence suggests that risk is associated with serum cholesterol in a continuous, graded fashion with no clear threshold below which further reductions in risk do not occur. In aggregate, the placebo-controlled statin trials strongly suggest that the magnitude of risk reduction is related to the degree of cholesterol lowering achieved. However, until recently, it was unknown whether intensified cholesterol lowering with higher doses of newer, more potent statins could bring further gains over a policy of moderate or conventional lipid lowering. This article summarizes the results of randomized trials comparing these two strategies in patients with a history of coronary artery disease.

Anticholesteremic Agents↗
PubMed2005

Prognostic implications of warfarin cessation after major trauma: a population-based cohort analysis.

BACKGROUND: Warfarin therapy is often withheld from elderly patients who fall or otherwise experience injury because of concerns regarding the long-term risk of hemorrhage in these individuals. We studied whether stopping warfarin after trauma is associated with a higher risk of subsequent adverse cardiovascular events. METHODS AND RESULTS: We conducted a retrospective, population-based, cohort study using linked administrative databases in the province of Ontario, Canada for the years 1992 to 2001. A total of 8450 elderly patients (age >65 years) who survived an incident of major trauma and were receiving warfarin before injury were followed up for a mean of 3.3 years. During the 6-month interval after trauma, 1827 (22%) patients discontinued warfarin, whereas 6623 (78%) patients continued warfarin. Warfarin cessation was not associated with an increased risk of subsequent stroke (hazard ratio [HR] 0.99, 95% CI 0.82 to 1.21) or myocardial infarction (HR 0.94, 95% CI 0.74 to 1.20) but was associated with a lower risk of major hemorrhage (HR 0.69, 95% CI 0.54 to 0.88) and a higher risk of venous thromboembolism (HR 1.59, 95% CI 1.07 to 2.36). Adjustment for baseline demographics, stroke risk factors, other comorbidities, and characteristics of the trauma did not materially change these findings. On-treatment analyses yielded similar results. CONCLUSIONS: Cessation of warfarin in elderly patients after major trauma was not associated with an increased risk of arterial thrombotic events but was associated with a significantly increased risk of venous thromboembolism.

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PubMed2005

Management of risk in peripheral artery disease: recent therapeutic advances.

Peripheral artery disease (PAD) is a problem frequently encountered by physicians who care for patients with coronary heart disease, diabetes mellitus, renal insufficiency, congestive heart failure, or stroke. Patients with PAD are at heightened risk of myocardial infarction and stroke and are 6 times more likely to die of cardiovascular causes than persons without the disease. There is an urgent need for therapies that reduce the incidence of vascular complications among patients with PAD. In recent years, a number of risk-lowering therapies have been validated by randomized controlled trials enrolling large numbers of patients with PAD. The available evidence supports aggressive lifestyle modification as well as the provision of an antiplatelet agent, an HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor, and an angiotensin-converting enzyme inhibitor for cardiovascular protection in patients with PAD. As a result of their high baseline risk and the proven effectiveness of these interventions, most patients with PAD will benefit substantially from aggressive medical therapy.

Arteries↗
PubMed2005

Cardiovascular risk prevention in peripheral artery disease.

Patients with peripheral arterial disease are at greatly elevated risk for stroke and myocardial infarction and are six times more likely to die from cardiovascular causes than those without the disease. The available evidence supports the provision of an antiplatelet agent, a statin, and an angiotensin-converting enzyme inhibitor for cardiovascular protection in these patients. When used together, these approaches are expected to produce a cumulative relative risk reduction of approximately 80%. Given the high baseline risk of this population and the effectiveness of these interventions, a combination of multiple drug therapies, in concert with aggressive lifestyle change and revascularization (where appropriate), can substantially reduce the burden of morbidity and mortality in patients with peripheral arterial disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

How does the prognosis of diabetes compare with that of established vascular disease? Insights from the Canadian Vascular Protection (VP) Registry.

BACKGROUND: Diabetes mellitus is a major risk factor for atherosclerotic cardiovascular disease. In a large, prospective, practice-based registry (the Vascular Protection Registry), we enrolled patients with vascular disease and/or diabetes, and compared the following features between diabetic and non-diabetic participants: (1) risk factor profiles, (2) utilization of cardioprotective medications, and (3) cardiovascular outcomes in short-term follow-up. METHODS: Patients were enrolled by participating physicians practicing in family medicine or specialty practices across Canada. The primary outcome was a composite of the first occurrence of any of the following vascular events: myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, or death. Patients were stratified according to the presence or absence of cardiovascular disease and diabetes. RESULTS: In all, 3297 patients were available for analysis (972 [30%] with diabetes but no cardiovascular disease; 899 [27%] with both diabetes and cardiovascular disease; and 1425 [43%] with cardiovascular disease but no diabetes). Most of the measured risk factors were worse for patients with diabetes. Compared to non-diabetic patients, diabetes was associated with substantial undertreatment with cardioprotective medications, including antiplatelet agents, beta blockers, and statins. During a mean follow-up of 10 (SD 3.3) months, patients with both diabetes and cardiovascular disease had the worst prognosis, with the primary outcome occurring at a rate of 16.3 per 100 person-years of follow-up. CONCLUSIONS: Patient registries provide a powerful tool for examining treatment patterns, risk factors, and outcomes. Patients with both cardiovascular disease and diabetes had the highest rates of adverse vascular outcomes. Possible reasons include relatively worse risk factor profiles and undertreatment with proven cardiovascular medications.

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PubMed2004

Progress in clinical neurosciences: pharmacotherapies for the secondary prevention of stroke.

Stroke is a leading cause of mortality and long-term disability worldwide. Survivors of a previous stroke or transient ischemic attack are vulnerable to further cerebrovascular events, as well as myocardial infarction, peripheral vascular disease, congestive heart failure and vascular death. Traditional approaches to the secondary prevention of stroke have included aspirin after ischemic stroke, warfarin for stroke associated with cardioembolic sources, and carotid endarterectomy for eligible candidates with significant carotid artery stenosis. In recent years, much evidence has emerged to support a broader array of pharmacotherapies, including newer antiplatelet agents, lipid lowering drugs, and several classes of blood pressure lowering therapies. Also under study are B vitamins for patients with cerebrovascular disease and hyper-homocysteinemia, and oral direct thrombin inhibitors for high-risk patients with atrial fibrillation. We review the literature to determine the clinical significance of these therapies, and provide recommendations regarding their use in the prevention of recurrent stroke.

Anticoagulants↗