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Biomedical subjects

D D Waters

Publications and source records attributed to D D Waters.

At least 19 recordsLinked to original sources
PubMed2001

Early pharmacologic intervention and plaque stability in acute coronary syndromes.

Remarkable therapeutic advances in the treatment of acute coronary syndromes (ACS) have been made with antiplatelet and antithrombotic therapy. However, these therapies alone do not appear to completely stabilize culprit lesions. Evidence from a variety of sources suggests that intensive cholesterol lowering with statins favorably influences culprit lesion stabilization in patients with ACS. Potential mechanisms of benefit include improvements in endothelial function, decreased propensity for platelet thrombus formation, and reduction in inflammation at the site of the lesion. The Myocardial Ischemia with Aggressive Cholesterol Lowering (MIRACL) study is the first large-scale clinical trial to examine whether these mechanisms translate into clinical-event reduction in patients with ACS as well as the substantial proved benefits in the chronic coronary syndromes. In this trial, early initiation of atorvastatin after an episode of unstable angina or non-Q-wave myocardial infarction reduced events over the ensuing 16 weeks. It is hoped that a growing awareness of the benefits of early statin therapy to stabilize culprit lesions in ACS will lead to an increase in the proportion of coronary patients who will receive this beneficial therapy.

Angina, Unstable↗
PubMed2001

What is the role of intensive cholesterol lowering in the treatment of acute coronary syndromes?

Cholesterol lowering with statins reduces coronary events in a primary-prevention setting and in patients with stable coronary disease. However, where the risk of a coronary event is highest, in the early months after an episode of unstable angina or non-Q-wave infarction, the effect of statin therapy has not been evaluated until recently. The lack of an early benefit in the 3 main statin trials in stable coronary disease may have discouraged this type of investigation. Yet, evidence suggests that intensive cholesterol lowering can rapidly influence several mechanisms intimately related to the pathogenesis of acute coronary syndromes; specifically, improvement in endothelial function, decreased propensity for platelet thrombus formation, and reduced inflammation. Furthermore, 3 nonrandomized, observational studies have recently reported an improved outcome in statin-treated compared with untreated patients after acute coronary syndromes.

Angina, Unstable↗
PubMed2001

Are we aggressive enough in lowering cholesterol?

To date, 5 major randomized, placebo-controlled statin trials--the Scandinavian Simvastatin Survival Study, West of Scotland Coronary Prevention Study, Cholesterol and Recurrent Events trial, Long-term Intervention with Pravastatin in Ischaemic Disease, and Air Force/Texas Coronary Atherosclerosis Prevention Study--have convincingly shown that total mortality and major coronary events can be significantly reduced by lowering levels of low-density lipoprotein cholesterol (LDL-C) with statin therapy. These results were achieved in a broad range of patients including those with and without a history of coronary artery disease and with elevated or average LDL-C levels. The results also support the large body of epidemiologic evidence demonstrating that the lower the cholesterol level, the lower the cardiovascular risk. Evidence now substantially supports the urgency of physicians to aggressively target the lowering of LDL-C levels for the primary and secondary prevention of coronary disease.

Anticholesteremic Agents↗
PubMed2001

What do the statin trials tell us?

The results of five large-scale, randomized, placebo-controlled trials, involving nearly 31,000 subjects, attest to the benefits of statins in the prevention of coronary events. Several key observations can be made on the basis of the evidence from these investigations. Of primary importance is the fact that statins reduce coronary event rates in patients with or without coronary heart disease. The percentage reduction in risk increases with each successive year of statin therapy. Moreover, the risk reduction is proportional to the reduction in low-density lipoprotein cholesterol. Subgroup analyses have demonstrated that the efficacy of statins extends to specific subgroups of patients, including women, people with diabetes, and older individuals. These agents also reduce the risk of stroke and transient ischemic attacks in patients with coronary disease. Both the randomized trials and widespread clinical experience have confirmed that statins are safe and do not increase the risk of cancer or mortality. Several markers of atherosclerotic risk are ameliorated by statins, although the clinical significance of this observation remains under investigation. The broad range of the therapeutic effects of statins yields safe, effective management of hypercholesterolemia in current practice while also providing a foundation for additional therapeutic refinements in the future.

Age Factors↗
PubMed2001

What do the statin trials tell us?

The results of 5 major placebo-controlled trials evaluating the effects of statins in approximately 31,000 individuals with and without known coronary disease have demonstrated the following: statins reduce the incidence of coronary events, the reduction in relative risk for coronary events increases with the duration of therapy, the reduction in coronary events is proportional to the reduction in low-density lipoprotein cholesterol (LDL-C) levels, and lower LDL-C levels are associated with lower event rates. The studies have also shown that statins are safe and effective in reducing the incidence of coronary events in women, individuals with diabetes, and patients older than 65 years of age and in reducing the risk of stroke and transient ischemic attacks in patients with coronary disease. Finally, studies indicate that statins ameliorate a variety of pathophysiologic processes that are associated with increased risk for atherosclerosis.

Anticholesteremic Agents↗
PubMed2000

Should intensive cholesterol lowering play a role in the management of acute coronary syndromes?

Although several large, well-controlled trials with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) demonstrate the benefits of cholesterol lowering on cardiovascular morbidity and mortality, these trials excluded patients with recent unstable angina or myocardial infarction. Thus, the potentially beneficial effects that may accrue from early statin therapy have not been apparent. Mechanistic and experimental studies show that benefits from statin therapy may include improved endothelial function, a decrease in platelet thrombus deposition, and a reduction in inflammation at the site of the lesion. Large-scale clinical trials are now under way to determine the effect of aggressive cholesterol lowering in patients with acute coronary syndromes. If the findings of the smaller studies are confirmed, statin therapy should be considered early after infarction or unstable angina.

Acute Disease↗
PubMed2000

Synergy between intracoronary stenting and abciximab in improving angiographic and clinical outcomes of primary angioplasty in acute myocardial infarction.

This study examined 650 consecutive patients who presented with an acute myocardial infarction and were treated with primary angioplasty within 12 hours of symptom onset between August 1995 and December 1998. Patients were placed into 4 treatment groups depending on the adjunctive therapy they received: group 1, percutaneous transluminal coronary angioplasty (PTCA) ("balloon PTCA alone"; n = 220); group 2, PTCA plus intracoronary stent placement ("stent"; n = 128); group 3, PTCA plus abciximab therapy ("abciximab"; n = 104); and group 4, PTCA plus intracoronary stent placement plus abciximab therapy ("stent/abciximab"; n = 198). The patients' clinical characteristics, severity of disease, and total ischemia time on presentation were similar. At baseline, abciximab and stent/abciximab groups had a higher incidence of thrombus on coronary angiography. Postprocedural quantitative coronary analysis showed a significantly larger minimum luminal diameter in the stent and stent/abciximab groups than PTCA alone. Overall, stents were most efficacious in reducing target vessel revascularization rate, whereas abciximab was associated with a higher postprocedural Thrombolysis In Myocardial Infarction-3 trial flow and less "no reflow." The best angiographic result was achieved in the stent/abciximab group. Similarly, the primary combined end point of death, myocardial infarction, and target vessel revascularization at 30 days was the lowest (6.1%) in the stent/abciximab group. The combination of abciximab and stenting in primary angioplasty for acute myocardial infarction is thus synergistic and is associated with improved angiographic and clinical results at 30-day follow-up.

Abciximab↗
PubMed2000

Short- and medium-term outcome differences in women and men after primary percutaneous transluminal mechanical revascularization for acute myocardial infarction.

Women presenting with acute myocardial infarction (AMI) have a higher mortality with conventional medical and thrombolytic therapy when compared with men. The outcome after primary percutaneous transluminal mechanical revascularization has not yet been fully investigated. This study was performed to compare the characteristics and the short- and medium-term outcomes of women and men with AMI treated with primary percutaneous revascularization. A total of 182 consecutive patients (62 women and 120 men) were included. Baseline clinical characteristics were similar except that women were older than men, presented more often in cardiogenic shock, and had smaller reference vessel diameters. Stents and abciximab were used equally, but abciximab was stopped more often in women before completion of the 12-hour infusion because of higher bleeding rates. Acute procedural success rates were similar (92% and 97%) but mortality was much higher in women, both at 30-day follow-up (100% vs 0.9%; p <0.05) and during a mean follow-up of 6.9 +/- 4.1 months (15% vs 4.4%; p <0.05). Women also experienced more unfavorable cardiovascular events (recurrent unstable angina or AMI, target vessel revascularization) than men. However, after control for baseline clinical differences in a multivariate analysis, gender was not an independent predictor of survival, whereas age, cardiogenic shock, and completion of a 12-hour abciximab infusion were.

Abciximab↗
PubMed2000

Comparison of electrocardiographic-gated technetium-99m sestamibi single-photon emission computed tomographic imaging and rest-redistribution thallium-201 in the prediction of myocardial viability.

Although the combined assessment of perfusion and function using rest electrocardiographic (ECG)-gated technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) imaging has been shown to improve sensitivity and accuracy over perfusion alone in the prediction of myocardial viability, no data are available comparing this technique with rest-redistribution thallium-201. Thirty patients with coronary artery disease and left ventricular dysfunction (ejection fraction < or = 40%) underwent rest-redistribution thallium-201 and rest ECG-gated Tc-99m sestamibi SPECT imaging before revascularization and rest ECG-gated Tc-99m sestamibi SPECT imaging at 1 or 6 weeks after revascularization. All thallium-201 and Tc-99m sestamibi images were interpreted by a consensus agreement of 3 experienced readers without knowledge of patient identity or time of imaging with Tc-99m sestamibi (before or after revascularization) using a 17-segment model. Concordance between techniques for the prediction of viability was 89% (kappa 0.556 +/- 0.109). With rest-redistribution thallium-201, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 95%, 59%, 88%, 78%, and 86%, respectively. With rest ECG-gated Tc-99m sestamibi SPECT imaging, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 96%, 55%, 87%, 80%, and 86%, respectively (p = NS vs rest-redistribution thallium-201). Although both techniques are comparable for detecting viable myocardium, rest ECG-gated Tc-99m sestamibi SPECT imaging allows direct assessment of both myocardial perfusion and ventricular function, which may be clinically useful in patients who require assessment of myocardial viability.

Coronary Disease↗
PubMed2000

A randomized placebo-controlled trial to assess the efficacy of antiinflammatory therapy with methylprednisolone in unstable angina (MUNA trial).

AIMS: The purpose of this study was to assess the efficacy of antiinflammatory therapy with methylprednisolone during the acute phase of unstable angina. METHODS: This is a randomized 'prospective' double-blind, placebo-controlled trial. Patients with the diagnosis of unstable angina were randomized to a 48-h course of methylprednisolone (n=81) or placebo (n=85). Patient care and therapy were otherwise decided by their attending cardiologist. The primary end-point was a composite of in-hospital recurrence of angina, silent ischaemia on Holter recording, emergency coronary revascularization, readmission with unstable angina, and myocardial infarction or death during the 30-day follow-up. RESULTS: The two groups were well balanced and had similar clinical characteristics at baseline. Forty-eight hours after randomization, mean C-reactive protein levels decreased by 2.6 mg. l(-1)in the methylprednisolone group, but increased by 1.6 mg. l(-1)in the placebo group (P=0.03). The primary end-point occurred in 44% of the methylprednisolone patients and in 33% of the placebo patients (P=0.12). Coronary revascularization rates were equal between the two groups (38% and 40%). When adjustment was made for the difference in revascularization times, a trend towards better event-free survival was seen in the control group (67% vs 57%;P=0.09). CONCLUSION: A 48 h course of antiinflammatory therapy with methylprednisolone given at the doses of this study did not improve the short-term outcome of patients with unstable angina.

Angina, Unstable↗
PubMed2000

Medical therapy versus revascularization: the atorvastatin versus revascularization treatment AVERT trial.

Although previous studies have shown that angioplasty improves exercise performance and reduces symptoms better than standard medical therapy in low risk, stable patients with coronary disease, none of these studies used aggressive cholesterol-lowering medical therapy. In addition, the event rate of death from myocardial infarction and other coronary events was found to be slightly higher in patients who had undergone angioplasty. The Atorvastatin versus Revascularization Treatment (AVERT) trial was the first study designed to compare the efficacy of aggressive cholesterol-lowering therapy versus percutaneous transluminal coronary angioplasty in low risk, stable patients with coronary artery disease. Results favour the use of aggressive lipid lowering over percutaneous transluminal coronary angioplasty in patients with mild to moderate coronary disease. Treatment with atorvastatin significantly reduced low density lipoprotein cholesterol levels, and was associated with a 36% reduction in ischemic events and a significant delay in time to first ischemic event.

Angioplasty, Balloon, Coronary↗