Showing papers by "Eugene Braunwald published in 2004"
TL;DR: Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery, and a substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.
Abstract: ContextAbout 5% of the US population is morbidly obese. This disease remains
largely refractory to diet and drug therapy, but generally responds well to
bariatric surgery.ObjectiveTo determine the impact of bariatric surgery on weight loss, operative
mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia,
hypertension, and obstructive sleep apnea).Data Sources and Study SelectionElectronic literature search of MEDLINE, Current Contents, and the Cochrane
Library databases plus manual reference checks of all articles on bariatric
surgery published in the English language between 1990 and 2003. Two levels
of screening were used on 2738 citations.Data ExtractionA total of 136 fully extracted studies, which included 91 overlapping
patient populations (kin studies), were included for a total of 22 094
patients. Nineteen percent of the patients were men and 72.6% were women,
with a mean age of 39 years (range, 16-64 years). Sex was not reported for
1537 patients (8%). The baseline mean body mass index for 16 944 patients
was 46.9 (range, 32.3-68.8).Data SynthesisA random effects model was used in the meta-analysis. The mean (95%
confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%)
for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding;
61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and
70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative
mortality (≤30 days) in the extracted studies was 0.1% for the purely restrictive
procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion
or duodenal switch. Diabetes was completely resolved in 76.8% of patients
and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more
of patients. Hypertension was resolved in 61.7% of patients and resolved or
improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients
and was resolved or improved in 83.6% of patients.ConclusionsEffective weight loss was achieved in morbidly obese patients after
undergoing bariatric surgery. A substantial majority of patients with diabetes,
hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete
resolution or improvement.
6,373 citations
TL;DR: Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen.
Abstract: background Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. methods We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). results The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan–Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. conclusions Among patients who have recently had an acute coronary syndrome, an intensive lipidlowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.
4,203 citations
TL;DR: Among patients with ACS, the early initiation of an aggressive simvastatin regimen resulted in a favorable trend toward reduction of major cardiovascular events and the trial did not achieve the prespecified end point.
Abstract: ContextLimited data are available evaluating how the timing and intensity of
statin therapy following an acute coronary syndrome (ACS) event affect clinical
outcome.ObjectiveTo compare early initiation of an intensive statin regimen with delayed
initiation of a less intensive regimen in patients with ACS.Design, Setting, and ParticipantsInternational, randomized, double-blind trial of patients with ACS receiving
40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n = 2265)
compared with ACS patients receiving placebo for 4 months followed by 20 mg/d
of simvastatin (n = 2232), who were enrolled in phase Z of the A to Z trial
between December 29, 1999, and January 6, 2003.Main Outcome MeasureThe primary end point was a composite of cardiovascular death, nonfatal
myocardial infarction, readmission for ACS, and stroke. Follow-up was for
at least 6 months and up to 24 months.ResultsAmong the patients in the placebo plus simvastatin group, the median
low-density lipoprotein (LDL) cholesterol level achieved while taking placebo
was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8
months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin
only group, the median LDL cholesterol level achieved at 1 month while taking
40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L)
at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%)
in the placebo plus simvastatin group experienced the primary end point compared
with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio
[HR], 0.89; 95% confidence interval [CI] 0.76-1.04; P =
.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in
the 2 groups (HR, 0.75; 95% CI, 0.57-1.00; P = .05)
but no differences were observed in other individual components of the primary
end point. No difference was evident during the first 4 months between the
groups for the primary end point (HR, 1.01; 95% CI, 0.83-1.25; P = .89), but from 4 months through the end of the study the primary
end point was significantly reduced in the simvastatin only group (HR, 0.75;
95% CI, 0.60-0.95; P = .02). Myopathy (creatine kinase
>10 times the upper limit of normal associated with muscle symptoms) occurred
in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving
lower doses of simvastatin, and in 1 patient receiving placebo (P = .02).ConclusionsThe trial did not achieve the prespecified end point. However, among
patients with ACS, the early initiation of an aggressive simvastatin regimen
resulted in a favorable trend toward reduction of major cardiovascular events.Published online August 30, 2004 (doi:10.1001/jama.292.11.1307).
1,312 citations
TL;DR: In patients with stable coronary heart disease and preserved left ventricular function who are receiving "current standard" therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors, there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes, myocardial infarction, or coronary revascularization.
Abstract: background Angiotensin-converting–enzyme (ACE) inhibitors are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure. ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure. methods In the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial, we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy. The trial was a doubleblind, placebo-controlled study in which 8290 patients were randomly assigned to receive either trandolapril at a target dose of 4 mg per day (4158 patients) or matching placebo (4132 patients). results The mean (±SD) age of the patients was 64±8 years, the mean blood pressure 133±17/78±10 mm Hg, and the mean left ventricular ejection fraction 58±9 percent. The patients received intensive treatment, with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs. The incidence of the primary end point — death from cardiovascular causes, myocardial infarction, or coronary revascularization — was 21.9 percent in the trandolapril group, as compared with 22.5 percent in the placebo group (hazard ratio in the trandolapril group, 0.96; 95 percent confidence interval, 0.88 to 1.06; P = 0.43) over a median follow-up period of 4.8 years. conclusions In patients with stable coronary heart disease and preserved left ventricular function who are receiving “current standard” therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease, there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes, myocardial infarction, or coronary revascularization.
1,079 citations
TL;DR: Clinical outcome by age in patients who were randomly assigned to an early invasive or conservative management strategy in the TACTICSTIMI 18 trial was analyzed to help resolve current uncertainties regarding appropriate management of elderly patients with nonST-segment elevation acute coronary syndromes.
Abstract: After acute coronary syndromes, older people have a larger risk for poor ischemic outcomes than younger people. Despite this increased risk, a routine early invasive strategy can significantly impr...
359 citations
TL;DR: Transient myocardial ischemia was associated with an immediate rise in circulating BNP levels, and the magnitude of rise was proportional to the severity of ischemIA, demonstrating an important link between the severityof an acute ischemic insult and the circulating levels of BNP.
326 citations
TL;DR: In a systematic overview of approximately 22 000 patients across the spectrum of ACS, enoxaparin is more effective than unfractionated heparin in preventing the combined end point of death or MI.
Abstract: ContextAntithrombin therapy has become a guidelines-recommended standard of
care in the treatment of acute coronary syndromes (ACS), but recent trials
comparing use of enoxaparin and unfractionated heparin in ACS have yielded
less robust efficacy and safety results than have earlier trials of these
antithrombin therapies.ObjectiveTo systematically evaluate the end points of all-cause death and nonfatal
myocardial infarction (MI), transfusion, and major bleeding observed in the
6 randomized controlled trials comparing enoxaparin and unfractionated heparin
in treatment of ACS.Data SourcesThe primary data sets for ESSENCE, A to Z, and SYNERGY were available
at the Duke Clinical Research Institute. Baseline characteristics and event
frequencies for TIMI 11B, ACUTE II, and INTERACT were provided by the principal
investigator of each study.Study SelectionAll 6 randomized controlled trials comparing enoxaparin and unfractionated
heparin in non–ST-segment elevation ACS were selected for analysis.Data ExtractionEfficacy and safety end points were extracted from the overall trial
populations and the subpopulation receiving no antithrombin therapy prior
to randomization.Data SynthesisSystematic evaluation of the outcomes for 21 946 patients was performed
using a random-effects empirical Bayes model. No significant difference was
found in death at 30 days for enoxaparin vs unfractionated heparin (3.0% vs
3.0%; odds ratio [OR], 1.00; 95% confidence interval [CI], 0.85-1.17). A statistically
significant reduction in the combined end point of death or nonfatal MI at
30 days was observed for enoxaparin vs unfractionated heparin in the overall
trial populations (10.1% vs 11.0%; OR, 0.91; 95% CI, 0.83-0.99; number needed
to treat, 107). A statistically significant reduction in the combined end
point of death or MI at 30 days was also observed for enoxaparin in the populations
receiving no prerandomization antithrombin therapy (8.0% vs 9.4%; OR, 0.81;
95% CI, 0.70-0.94; number needed to treat, 72). No significant difference
was found in blood transfusion (OR, 1.01; 95% CI, 0.89-1.14) or major bleeding
(OR, 1.04; 95% CI, 0.83-1.30) at 7 days after randomization in the overall
safety population or in the population of patients receiving no prerandomization
antithrombin therapy.ConclusionIn a systematic overview of approximately 22 000 patients across
the spectrum of ACS, enoxaparin is more effective than unfractionated heparin
in preventing the combined end point of death or MI.
303 citations
TL;DR: In patients receiving tirofiban and aspirin, enoxaparin is a suitable alternative to unfractionated heparin for treatment of non-ST-elevation ACS and is consistent with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors.
Abstract: ContextEnoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban
with unfractionated heparin independently have shown superior efficacy over
unfractionated heparin alone in patients with non–ST-elevation acute
coronary syndromes (ACS) It is not clear if combining enoxaparin with glycoprotein
IIb/IIIa inhibitors is as safe or as effective as the current standard combination
of unfractionated heparin with glycoprotein IIb/IIIa inhibitorsObjectiveTo assess efficacy and safety of the combination of enoxaparin and tirofiban
compared with unfractionated heparin and tirofiban in patients with non–ST-elevation
ACSDesign, Setting, and ParticipantsA prospective, international, open-label, randomized, noninferiority
trial of 1 mg/kg of enoxaparin every 12 hours (n = 2026) compared with weight-adjusted
intravenous unfractionated heparin (n = 1961) in patients with non–ST-elevation
ACS receiving tirofiban and aspirin Phase A of the A to Z trial was conducted
between December 1999 and May 2002Main Outcome MeasuresDeath, recurrent myocardial infarction, or refractory ischemia at 7
days in the intent-to-treat population with boundaries set for superiority
and noninferiority Safety based on measures of bleeding using the Thrombolysis
in Myocardial Infarction (TIMI) classification systemResultsA total of 169 (84%) of 2018 patients randomized to enoxaparin experienced
death, myocardial infarction, or refractory ischemia at 7 days compared with
184 (94%) of 1952 patients randomized to unfractionated heparin (hazard ratio
[HR], 088; 95% confidence interval [CI], 071-108) This met the prespecified
criterion for noninferiority All components of the composite primary and
secondary end points favored enoxaparin except death, which occurred in only
1% of patients (23 for enoxaparin and 17 for unfractionated heparin) Rates
for any TIMI grade bleeding were low (30% for enoxaparin and 22% for unfractionated
heparin; P = 13) Using a worst-case approach that
combined 2 independent bleeding evaluations, use of enoxaparin was associated
with 1 additional TIMI major bleeding episode for each 200 patients treatedConclusionsIn patients receiving tirofiban and aspirin, enoxaparin is a suitable
alternative to unfractionated heparin for treatment of non–ST-elevation
ACS The 12% relative and 1% absolute reductions in the primary end point
in favor of enoxaparin met criterion for noninferiority and are consistent
with prior trials performed without the use of glycoprotein IIb/IIIa inhibitors
231 citations
TL;DR: Increased concentrations of BNP at initial presentation of patients with STEMI are associated with impaired reperfusion after fibrinolysis and higher short-term risk of mortality, and support the value of combining markers of hemodynamic stress with traditional approaches to risk assessment in acute myocardial infarction.
213 citations
TL;DR: In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide, which suggests that a multimarker approach may aid the initial risk assessment of UA-N STEMI, especially in women.
Abstract: Background— Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI). Methods and Results— In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women ...
TL;DR: Among patients who have recently had an acute coronary syndrome, an intensive lipidlowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen.
Abstract: background Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. methods We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). results The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan–Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. conclusions Among patients who have recently had an acute coronary syndrome, an intensive lipidlowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.
TL;DR: CKD was associated with a heightened risk for all major CV events after MI, particularly among subjects with an estimated glomerular filtration rate <45 mL · min−1 · 1.73 m−2, and Randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function.
Abstract: Background— Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease (CKD) have an increased risk of death after myocardial infarction (MI) that is not fully explained by associated comorbidities. Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized. Methods and Results— We calculated the estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days after MI) with left ventricular ejection fraction ≤40% and serum creatinine <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR. Subjects with reduced eGFR were older and had more extensive comorbidities. The multivariable adjusted risk ratio for total morta...
TL;DR: In patients who survived myocardial infarction with left ventricular dysfunction, diabetes increased risk of death from all causes even after controlling for differences in other risk factors.
Abstract: Background Diabetes is a major risk factor for developing coronary heart disease. In patients with diabetes who survived myocardial infarction (MI), less is known about subsequent morbidity and mortality. We evaluated the effects of diabetes in post-MI patients with left ventricular dysfunction on cardiovascular events and death. Methods The Survival and Ventricular Enlargement, a randomized, double-blind, placebo-controlled multicenter trial, evaluated the efficacy of captopril vs placebo in 2231 patients following acute MI with left ventricular dysfunction defined as an ejection fraction less than or equal to 40%. Patients were randomly assigned to captopril or placebo 3 to 16 days following MI and were followed up for 2 to 5 years (mean, 3.5 years). Results Among the 2231, 496 (22.2%) were patients with a history of diabetes, of which 168 (33.9%) were treated with insulin. Patients with diabetes were significantly older; more likely to be women; have a history of prior MI or hypertension; be obese or manifest Killip class II or greater; and have higher systolic blood pressure, pulse pressure, and heart rate, as well as lower ejection fraction. During follow-up, 31.3% of patients with diabetes and 20.1% of nondiabetic patients died (P Conclusions In patients who survived MI with left ventricular dysfunction, diabetes increased risk of death from all causes even after controlling for differences in other risk factors. Patients with diabetes treated with insulin have a particularly higher mortality risk. Patients with diabetes who survived MI with left ventricular dysfunction, in particular those receiving insulin, are at high risk of subsequent mortality and cardiovascular events and thus require intensive risk factor modification, as well as evaluation for novel therapies.
TL;DR: In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS.
Abstract: Aims To determine the association of glomerular filtration rate (GFR) with clinical outcomes in the setting of non-ST-segment elevation acute coronary syndromes (NSTE-ACS).
Methods and results Data were pooled from five NSTE-ACS TIMI trials (TIMI 11A and B, TIMI 12, OPUS-TIMI 16 and TACTICS-TIMI 18) and were available in 13 307 patients. GFR was assessed as a continuous and a categorical variable (normal: ⩾90 mL/min/1.73 m2, n =4952; mildly decreased: 60-89 mL/min/1.73 m2, n =6262; and moderately to severely decreased GFR: <60 mL/min/1.73 m2, n =2093). There was an independent association between decreasing GFR and mortality at 30 days (OR 1.19, 95% CI 1.12–1.27, p <0.001) and at 6 months (OR 1.16, 95% CI 1.11–1.22, p <0.001). The combination of TIMI risk score (TRS) and decreasing GFR provided further mortality risk stratification with highest 30-day and 6-month mortality rates among patients with the lowest GFR who also had a TRS⩾5 (9.1% and 15.4%, respectively). Decreasing GFR was also independently associated with stroke and recurrent ischaemia at 30-days as well as with major bleeding ( p <0.001).
Conclusion In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS.
TL;DR: Among patients with UA/NSTEMI, elevated BNP levels are associated with tighter culprit stenosis, higher CTFC, and LAD involvement, and may partly explain the association between Elevated BNP and adverse outcomes.
TL;DR: The investigators concluded that the A to Z trial did not achieve the prespecified end point of benefit with early high-dose simvastatin therapy, but it demonstrated that aggressive LDL cholesterol lowering following ACS prevents death and major cardiovascular events.
Abstract: Study Question: Phase Z of the A to Z trial was designed to evaluate a strategy of early initiation of intensive treatment with simvastatin (80 mg) in ACS patients compared with a delayed, less intensive strategy. Methods: The study was a randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n=2265) compared with placebo for 4 months followed by 20 mg/d of simvastatin (n=2232). The primary end point was a composite of cardiovascular death, nonfatal MI, readmission for ACS, and stroke. Follow-up was at least 6 months and up to 24 months. Results: Among the patients in the placebo plus simvastatin group, the median low-density lipoprotein (LDL) cholesterol level achieved while taking placebo was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin-only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%) in the placebo plus simvastatin group experienced the primary end point compared with 309 (14.4%) in the simvastatin-only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95% confidence interval [CI] 0.76–1.04; p=0.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in the two groups (HR, 0.75; 95% CI, 0.57–1.00; p =0.05) but no differences were observed in other individual components of the primary end point. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95% CI, 0.83–1.25; p =0.89), but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin-only group (HR, 0.75; 95% CI, 0.60–0.95; p =0.02). Myopathy (creatine kinase >10 times the upper limit of normal associated with muscle symptoms) occurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving lower doses of simvastatin, and in 1 patient receiving placebo ( p =0.02). Conclusions: The investigators concluded that the trial did not achieve the prespecified end point of benefit with early high-dose simvastatin therapy. Perspective: Early initiation of an intensive simvastatin regimen when compared with the delayed initiation of a less intensive simvastatin regimen did not show significant clinical benefit. The findings from the MIRACL and PROVE-IT studies, however, demonstrated that aggressive LDL cholesterol lowering following ACS prevents death and major cardiovascular events. The unfavorable risk-benefit relationship observed in the A to Z trial should not diminish the value of intensive statin treatment in secondary prevention, including ACS patients. For now, though, the 80-mg/d dose of simvastatin should be used with caution, particularly because other effective agents are available. DM
TL;DR: A simple risk index from baseline clinical variables routinely obtained at the first patient encounter predicted mortality in a large unselected heterogeneous group of patients with STEMI.
TL;DR: The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI.
TL;DR: The TIMI IIIB and TACTICS-TIMI 18 trials as mentioned in this paper were two trials of an early invasive strategy in unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI) that were conducted nearly a decade apart but with virtually identical enrollment criteria and designs, except that upstream glycoprotein IIb/IIIa inhibition was mandated and coronary artery stenting was routinely used in TACS-TMI 18.
Abstract: Background— TIMI IIIB and TACTICS-TIMI 18 were 2 trials of an early invasive strategy in unstable angina (UA)/non–ST-elevation myocardial infarction (NSTEMI) that were conducted nearly a decade apart but with virtually identical enrollment criteria and designs, except that upstream glycoprotein IIb/IIIa inhibition was mandated and coronary artery stenting was routinely used in TACTICS-TIMI 18. We sought to examine the effect of these advances on clinical outcomes and the benefits of an early invasive strategy in UA/NSTEMI. Methods and Results— Patients were stratified on the basis of their TIMI risk score into low-, intermediate-, and high-risk categories. Within each risk category, the rates of clinical outcomes and the benefit of an early invasive strategy were compared. Compared with patients in TIMI IIIB and adjusting for baseline risk, patients in TACTICS-TIMI 18 had lower rates of death, MI, or rehospitalization for acute coronary syndromes (OR, 0.62; P<0.0001). Across both trials, the benefit of an...
TL;DR: A prolonged symptom to treatment time among STEMI patients is associated with impaired myocardial perfusion independent of epicardial flow both immediately after fibrinolytic administration and after rescue/adjunctive PCI, and these data provide a pathophysiologic link between prolonged symptoms due to vessel occlusion, impaired my cardiac perfusion, and poor clinical outcomes.
TL;DR: When a conservative approach to catheterisation and PCI was planned for ACS patients receiving tirofiban and aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs UFH.
Abstract: Aims In high risk patients with non-ST elevation acute coronary syndromes (ACS), enoxaparin is generally preferred to unfractionated heparin (UFH). However, less is known about the relative merits of these two forms of heparin in patients receiving concomitant glycoprotein IIb/IIIa inhibitors.
Methods and results The A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987 patients with non-ST elevation ACS were randomised to receive either enoxaparin or UFH in combination with aspirin and tirofiban. Inclusion required either ST depression or cardiac biomarker elevation. While the selection of an early management strategy (invasive or conservative) was at the discretion of the local investigator, investigators were asked to designate their plans for an invasive or conservative strategy on the case record form. An early conservative strategy was specified for 1778 patients (45%); this subgroup forms the population for the present analyses. Among patients with a planned conservative strategy, baseline characteristics were similar between those randomised to UFH ( n =872) and those randomised to enoxaparin ( n =906). The primary endpoint of death, new MI, or documented refractory ischaemia within 7 days of randomisation occurred in 10.6% of patients randomised to UFH and 7.7% of patients randomised to enoxaparin (HR 0.72; 95% CI 0.53–0.99; p =0.04). The combined rate of TIMI major, minor, or loss no-site bleeding was 1.3% in patients treated with UFH and 1.8% in those treated with enoxaparin ( p = ns ).
Conclusions When a conservative approach to catheterisation and PCI was planned for ACS patients receiving tirofiban and aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs UFH.
TL;DR: A new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography, and attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI.
Abstract: The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the "trifecta," defined as the presence of TFG 3, MPG 3, and complete (> or =70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography.
TL;DR: This study links restoration of epicardial flow, normal myocardial perfusion, and complete ST-segment resolution with higher levels of platelet glycoprotein IIb/IIIa receptor occupancy after therapy with eptifibatide administered with tenecteplase.
Abstract: Background— Paradoxically, fibrinolytic agents may systemically activate platelets, which in turn secrete plasminogen activator inhibitor (PAI-1), an antagonist of the fibrinolytic process in proportion to total body platelet mass. We hypothesized that improved epicardial patency, myocardial perfusion, and ST-segment resolution would be associated with higher levels of platelet receptor occupancy (RO) by a glycoprotein IIb/IIIa antagonist in ST-elevation MI (STEMI). Methods and Results— Patients were drawn from the low-dose tenecteplase plus eptifibatide arm of the INTEGRITI study. Angiographic and platelet RO data were analyzed at 2 independent core laboratories. To take into account the absolute platelet count and receptors available for cross-linking, absolute platelet count was multiplied by percent of available receptors to obtain the index of the absolute number of receptors available (IANRA). Percent RO was higher among patients with a patent artery (TIMI flow grade 2/3; 78.2±9.2, n=63 versus 63.9±...
TL;DR: A novel risk score based on admission clinical variables can be used to estimate the likelihood of in-hospital coronary artery bypass graft surgery (CABG) and may assist in the identification of patients who might derive optimal benefit from early initiation of clopidogrel therapy.
TL;DR: Despite a higher risk profile, patients with more severe HF were treated less aggressively than patients without HF, and angiotensin-inhibitors and beta-blockers were not optimally utilised in patients with HF following MI.
Abstract: Aims To define the clinical characteristics, co-morbidities, treatment, and clinical outcomes of patients with varying degrees of heart failure (HF) complicating ST-elevation myocardial infarction (STEMI), and to identify patients at high risk for HF following fibrinolysis.
Methods and results 15,078 STEMI patients enrolled in a worldwide fibrinolytic trial (InTIME-II) were categorised into one of four hierarchical, mutually exclusive groups of HF: shock (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=719\) \end{document}, 5%); severe HF (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=1082\) \end{document}, 7%); mild HF (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=1619\) \end{document}, 11%); no HF (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=11,658\) \end{document}, 77%). In a multivariable model, anterior MI (OR 1.8, 95% CI [1.6; 1.9]), age ⩾65 (OR 1.8 [1.6; 2.0]), prior HF (OR 3.3 [2.6; 4.2]), and creatinine clearance \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({<}\) \end{document}60 mL/min (OR 1.8 [1.6; 2.1]) were the four most powerful correlates of HF. Although 30-day mortality was sixfold higher for patients with HF (18.9% vs. 3.1%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{<}0.0001\) \end{document}), these patients were less likely to undergo angiography (30% vs. 40%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{<}0.0001\) \end{document}) and revascularisation (19% vs. 25%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{<}0.0001\) \end{document}), than patients without HF. Likewise, angiotensin-inhibitors and β-blockers were not optimally utilised in patients with HF following MI.
Conclusions During the index admission following fibrinolysis 23% of patients had HF. Despite a higher risk profile, patients with more severe HF were treated less aggressively than patients without HF.
TL;DR: A higher platelet count is independently associated with the presence of residual thrombus in the infarct-related artery after administration of fibrinolytic therapy, even after multivariate adjustment.
Abstract: A higher platelet count is independently associated with the presence of residual thrombus in the infarct-related artery after administration of fibrinolytic therapy, even after multivariate adjustment.
TL;DR: It is demonstrated that more rapid ST res on continuous ECG monitoring is associated with improved myocardial perfusion after thrombolytic administration.
Journal Article•
TL;DR: Management of suspected UA/NSTEMI has four components: initial evaluation and management; hospital care; coronary revascularization; and hospital discharge and post-hospital care.
Abstract: Each year, more than 1 million patients are admitted to U.S. hospitals because of unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). To help standardize the assessment and treatment of these patients, the American College of Cardiology and the American Heart Association convened a task force to formulate a management guideline. This guideline, which was published in 2000 and updated in 2002, highlights recent medical advances and is a practical tool to help physicians provide medical care for patients with UA/NSTEMI. Management of suspected UA/NSTEMI has four components: initial evaluation and management; hospital care; coronary revascularization; and hospital discharge and post-hospital care. Part I of this two-part article discusses the first two components of management. During the initial evaluation, the history, physical examination, electrocardiogram, and cardiac biomarkers are used to determine the likelihood that the patient has UA/NSTEMI and to aid in risk assessment when the diagnosis is established. Hospital care consists of appropriate initial triage and monitoring. Medical treatment includes anti-ischemic therapy (oxygen, nitroglycerin, beta blocker), antiplatelet therapy (aspirin, clopidogrel, platelet glycoprotein IIb/IIIa inhibitor), and antithrombotic therapy (heparin, low-molecular-weight heparin).