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Harvey White

Publications and source records attributed to Harvey White.

At least 19 recordsLinked to original sources
PubMed2005

Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both.

BACKGROUND: The risk of sudden death from cardiac causes is increased among survivors of acute myocardial infarction with reduced left ventricular systolic function. We assessed the risk and time course of sudden death in high-risk patients after myocardial infarction. METHODS: We studied 14,609 patients with left ventricular dysfunction, heart failure, or both after myocardial infarction to assess the incidence and timing of sudden unexpected death or cardiac arrest with resuscitation in relation to the left ventricular ejection fraction. RESULTS: Of 14,609 patients, 1067 (7 percent) had an event a median of 180 days after myocardial infarction: 903 died suddenly, and 164 were resuscitated after cardiac arrest. The risk was highest in the first 30 days after myocardial infarction--1.4 percent per month (95 percent confidence interval, 1.2 to 1.6 percent)--and decreased to 0.14 percent per month (95 percent confidence interval, 0.11 to 0.18 percent) after 2 years. Patients with a left ventricular ejection fraction of 30 percent or less were at highest risk in this early period (rate, 2.3 percent per month; 95 percent confidence interval, 1.8 to 2.8 percent). Nineteen percent of all sudden deaths or episodes of cardiac arrest with resuscitation occurred within the first 30 days after myocardial infarction, and 83 percent of all patients who died suddenly did so in the first 30 days after hospital discharge. Each decrease of 5 percentage points in the left ventricular ejection fraction was associated with a 21 percent adjusted increase in the risk of sudden death or cardiac arrest with resuscitation in the first 30 days. CONCLUSIONS: The risk of sudden death is highest in the first 30 days after myocardial infarction among patients with left ventricular dysfunction, heart failure, or both. Thus, earlier implementation of strategies for preventing sudden death may be warranted in selected patients.

Aged↗
PubMed2004

Management of patients admitted with an Acute Coronary Syndrome in New Zealand: results of a comprehensive nationwide audit.

AIMS: To audit all patients presenting to a New Zealand hospital with a myocardial infarction or unstable angina (an acute coronary syndrome [ACS]) over a 14-day period, to assess their number, presentation type and patient management during the hospital admission. METHODS: We formed a group of clinicians to lead the local audit process with one representative for each hospital (n=36) that admitted ACS patients. A comprehensive data form was used to record individual patient information for patients admitted between 0000 hours on 13 May 2002 to 2400 hours on 26 May 2002. RESULTS: 930 patients were admitted with a suspected or definite ACS: 11% with a ST-segment-elevation myocardial infarction (STEMI), 31% with a non-STEMI, 36% with unstable angina pectoris (UAP), and 22% with another cardiac or medical diagnosis. Cardiac investigations were limited: echocardiogram (20%), exercise treadmill test (20%), cardiac angiogram (21%). In-hospital revascularisation rates were low for those patients with a definite presentation with an ACS (STEMI, non-STEMI, UAP, n=721). Percutaneous coronary intervention (PCI) rates were 13%, 8%, and 4%--with coronary artery bypass grafting (CABG) rates being 4%, 3%, and 4% respectively. The use of discharge medications of proven benefit was also generally low (n=695): aspirin (82%), clopidogrel (8%), beta-adrenergic blockers (63%), angiotensin converting enzyme (ACE) inhibitors (43%), and statins (55%). CONCLUSIONS: A collaborative group of clinicians has performed a nationwide audit of acute coronary syndrome patients, which has demonstrated low levels of investigations, evidence-based treatments, and revascularisation. There is a need for a comprehensive national strategy--particularly for continuing audit of the treatment of patients presenting with a suspected or definite acute coronary syndrome to a New Zealand hospital.

Adult↗
PubMed2004

Acute Coronary Syndrome patients in New Zealand receive less invasive management when admitted to hospitals without invasive facilities.

AIM: To compare differences in the presentation and management of acute coronary syndrome (ACS) patients presenting to interventional versus non-interventional New Zealand hospitals. METHODS: We assessed the data collected by the New Zealand Cardiac Society ACS Audit Group over 14 days from each hospital in New Zealand (n=36) that admits ACS patients. Patient management at intervention centres (5 public, 3 private) was compared with non-intervention centres (28 public). Investigations and revascularisation procedures performed on transferred patients were attributed to the referring centre. RESULTS: From 0000 hours on 13 May 2002 to 2400 hours on 26 May 2002, 930 patients were admitted to a New Zealand hospital with a suspected or definite ACS: ST-segment-elevation myocardial infarction [STEMI] (11%), non-STEMI (31%), unstable angina pectoris [UAP] (36%), or another cardiac or medical diagnosis (22%). Patients admitted to a non-intervention centre (n=612) were the same age (median 70 years) with similar risk factors, but were more likely to be Maori (8.2% vs 3.8%, p=0.0063) and were less likely to have a history of prior cardiac angiography (26% vs 28%, p=0.02) or percutaneous coronary intervention [PCI] (9.6% vs 14%, p=0.03) than patients admitted to an intervention centre (n=318). Patients admitted to a non-intervention centre were more likely to have a chest X-ray (88% vs 81%, p<0.0024), as likely to have an exercise treadmill test (20% vs 22%, p=0.39), but less likely to receive an echocardiogram (17% vs 26%, p<0.0005), a cardiac angiogram (17% vs 30%, p<0.0001), or neither a treadmill nor a cardiac angiogram (68% vs 53%, p<0.0001) for cardiac risk assessment. For patients with a definite ACS presentation (STEMI, Non-STEMI, UAP, n=721), PCI was performed less often for patients admitted to non-intervention centres: 3% vs 14% (p<0.0001), although the rate of coronary artery bypass grafting was similar: 3% vs 5% (p=0.16). CONCLUSION: Patients admitted to a hospital without cardiac interventional facilities receive fewer investigations and less revascularisation than patients admitted to Intervention Centres. Hence patients admitted with an acute coronary syndrome in New Zealand receive inequitable management. A comprehensive National strategy is needed to improve access to optimal cardiac care.

Adult↗
PubMed2004

Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial.

CONTEXT: Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. OBJECTIVES: To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. DESIGN, SETTING, AND PARTICIPANTS: The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. INTERVENTIONS: Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. MAIN OUTCOME MEASURES: The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. RESULTS: The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). CONCLUSIONS: Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.

Aged↗
PubMed2004

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.

Adult↗
PubMed2003

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. METHODS: Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. RESULTS: During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. CONCLUSIONS: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.

Aged↗
PubMed2003

Cardiogenic shock caused by right ventricular infarction: a report from the SHOCK registry.

OBJECTIVES: The purpose of this study was to determine the characteristics and outcomes of patients with acute myocardial infarction (MI) complicated by cardiogenic shock due to predominant right ventricular (RV) infarction. BACKGROUND: Although RV infarction has been shown to have favorable long-term outcomes, the influence of RV infarction on mortality in cardiogenic shock is unknown. METHODS: We evaluated 933 patients in cardiogenic shock due to predominant RV (n = 49) or left ventricular (LV) failure (n = 884) in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK? (SHOCK) trial registry. RESULTS: Patients with predominant RV shock were younger, with a lower prevalence of previous MI (25.5 vs. 40.1%, p = 0.047), anterior MI, and multivessel disease (34.8 vs. 77.8%, p < 0.001) and a shorter median time between the index MI and the diagnosis of shock (2.9 vs. 6.2 h, p = 0.003) in comparison to patients with LV shock. In-hospital mortality was 53.1% versus 60.8% (p = 0.296) for patients with predominant RV and LV shock, respectively, and the influence of revascularization on mortality was not different between groups. Multivariate analysis revealed that RV shock was not an independent predictor of lower in-hospital mortality (odds ratio 1.07, 95% confidence interval 0.54 to 2.13). CONCLUSIONS: Despite the younger age, lower rate of anterior MI, and higher prevalence of single-vessel coronary disease of RV compared with LV shock patients, and their similar benefit from revascularization, mortality is unexpectedly high in patients with predominant RV shock and similar to patients with LV shock.

Aged↗
PubMed2003

The evolving role of direct thrombin inhibitors in acute coronary syndromes.

The central role of thrombin in the initiation and propagation of intravascular thrombus provides a strong rationale for direct thrombin inhibitors in acute coronary syndromes (ACS). Direct thrombin inhibitors are theoretically likely to be more effective than indirect thrombin inhibitors, such as unfractionated heparin or low-molecular-weight heparin, because the heparins block only circulating thrombin, whereas direct thrombin inhibitors block both circulating and clot-bound thrombin. Several initial phase 3 trials did not demonstrate a convincing benefit of direct thrombin inhibitors over unfractionated heparin. However, the Direct Thrombin Inhibitor Trialists' Collaboration meta-analysis confirms the superiority of direct thrombin inhibitors, particularly hirudin and bivalirudin, over unfractionated heparin for the prevention of death or myocardial infarction (MI) during treatment in patients with ACS, primarily due to a reduction in MI (odds ratio, 0.80; 95% confidence interval, 0.70 to 0.91) with little impact on death. The absolute risk reduction in the composite of death or MI at the end of treatment (0.8%) was similar at 30 days (0.7%), indicating no loss of benefit after cessation of therapy. Supportive evidence for the superiority of direct thrombin inhibitors over heparin derives from the recently reported Hirulog and Early Reperfusion or Occlusion (HERO)-2 randomized trial with ST-segment elevation ACS, which demonstrated a similar benefit of bivalirudin over heparin for the prevention of death or MI at 30 days (absolute risk reduction 1.0%), again primarily due to a reduction in MI during treatment (odds ratio, 0.70; 95% confidence interval, 0.56 to 0.87), with little impact on death. Further evaluation of hirudin and bivalirudin in the antithrombotic management of patients with ACS is warranted.

Acute Disease↗
PubMed2002

Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?

BACKGROUND: The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that pravastatin significantly reduced mortality and coronary heart disease (CHD) events in 9014 patients with known CHD and total cholesterol 4.0 to 7.0 mmol/L at baseline. Secondary objectives included assessment of CHD event reduction according to lipid levels. METHODS AND RESULTS: We investigated the relationships of baseline and on-study lipids with subsequent CHD events in separate Cox models. Treatment effect on CHD event reduction was examined by baseline lipids and after adjustment for on-study lipid levels. Baseline lipids were significant predictors of CHD events. The adjusted relative risk per mmol/L (on placebo) was 1.24 (P=0.004) for total cholesterol, 1.28 (P=0.002) for low-density lipoprotein cholesterol, and 0.52 (P=0.004) for high-density lipoprotein cholesterol. Apolipoproteins A1 and B were strong predictors (each P=0.001). Pravastatin reduced the risk of the composite outcome of fatal CHD or nonfatal myocardial infarction by 24% (95% confidence interval [CI], 15% to 32%) and the expanded end point of fatal CHD, nonfatal myocardial infarction, unstable angina, or coronary revascularization by 17% (95% CI, 10% to 24%). Similar relative effects were observed for different categories of baseline lipids. The proportion of treatment effect explained by on-study lipid levels was 67% (95% CI, 27% to 106%) for the composite and 97% (95% CI, 49% to 145%) for the expanded end point. The most important lipids associated with event reduction were apolipoprotein B, low-density lipoprotein cholesterol, and the combination of total and high-density lipoprotein cholesterol. CONCLUSIONS: Changes in lipid levels can explain all or most of the observed benefit of pravastatin. Some treatment effect may also be mediated through nonlipid changes.

Adult↗
PubMed2002

Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials.

BACKGROUND: Platelet glycoprotein IIb/IIIa inhibitors have been shown to reduce cardiac complications in patients undergoing percutaneous coronary intervention. The clinical efficacy of these drugs in acute coronary syndromes, however, is still unclear. We did a meta-analysis of all large randomised trials designed to study the clinical efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. METHODS: Inclusion criteria were: randomisation of patients with acute coronary syndromes but without persistent ST elevation; comparison of a glycoprotein IIb/IIIa inhibitor with placebo or control therapy; non-recommendation of early coronary revascularisation during study-drug infusion; and enrollment of at least 1000 patients. Data on individual patients were obtained from all participants in these trials. FINDINGS: Six trials, enrolling 31402 patients, fulfilled the inclusion criteria. 30 days after randomisation, 3530 (11.2%) patients died or developed a myocardial infarction. At 30 days, a 9% reduction in the odds of death or myocardial infarction was seen with glycoprotein IIb/IIIa inhibitors compared with placebo or control (10.8% [1980/18297] vs 11.8% [1550/13105] events; odds ratio 0.91 [95% CI 0.84-0.98]; p=0.015). The relative treatment benefit was similar in subgroups of patients according to important clinical baseline characteristics; hence, the absolute treatment benefit was largest in high-risk patients. An unexpected and significant interaction was seen between sex and allocated treatment, with a treatment benefit in men (0.81 [0.75-0.89] but not in women (1.15 [1.01-1.30]). However, once patients were stratified according to troponin concentration, there was no evidence of a sex difference in treatment response, and a risk reduction was seen in men and women with raised troponin concentrations. Major bleeding complications were increased by glycoprotein IIb/IIIa inhibitors (2.4% [445/18297] vs 1.4% [180/13105]; p<0.0001), but intracranial bleeding was not (16 [0.09%] vs 8 [0.06%]; p=0.40). INTERPRETATION: Glycoprotein IIb/IIIa inhibitors reduce the occurrence of death or myocardial infarction in patients with acute coronary syndromes not routinely scheduled for early revascularisation. The event reduction is greatest in patients at high risk of thrombotic complications. Treatment with a glycoprotein IIb/IIIa inhibitor might therefore be considered especially in such patients early after admission, and continued until a decision about early coronary revascularisation has been made.

Aged↗
PubMed2002

Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender.

BACKGROUND: These studies were conducted to determine whether bivalirudin clearance and pharmacodynamics are dependent on dose, renal function, or gender. METHODS: Two studies were performed. The first comprised 25 patients who were undergoing percutaneous coronary intervention-8 with normal renal function, 11 with mild renal impairment, and 6 with moderate renal impairment. Each patient received a bolus dose of bivalirudin (1 mg/kg) followed by an infusion (2.5 mg/kg per hour for 4 of 6 hours, then 0.5 mg/kg per hour for 4 of 6 hours). The second study enrolled 8 volunteers with severe renal impairment who received a bivalirudin bolus of 1 mg/kg, followed by an infusion of 0.5 mg/kg per hour for 10 hours. Bivalirudin in plasma and urine was assayed with a newly developed, highly specific liquid chromatography-mass spectrometry assay. RESULTS: Clearances at the two infusion doses did not differ significantly (3.23 mL/min per kilogram and 3.16 mL/min per kilogram). There was no statistically significant difference in area under the concentration-time curve (AUC) and in plasma clearance between patients with normal renal function and those with mild renal impairment. Patients with moderate and severe renal impairment had reductions in plasma clearance of 21% and 24%, respectively. The level of anticoagulation(activated clotting time) was similar between groups. There was no difference between male and female patients. CONCLUSION: The clearance of bivalirudin is dependent on renal function but independent of dose and gender. Approximately 20% of unchanged drug is cleared via the kidney, and the remainder presumably undergoes proteolysis intracellularly. The pharmacodynamics of bivalirudin are dose-dependent and gender-independent. Bivalirudin kinetics are linear in the dose ranges that are used in percutaneous coronary intervention and that are under investigation for use in acute coronary syndromes.

Aged↗