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M A Pfeffer

Publications and source records attributed to M A Pfeffer.

At least 19 recordsLinked to original sources
PubMed2001

Recovery of ventricular function after myocardial infarction in the reperfusion era: the healing and early afterload reducing therapy study.

BACKGROUND: Patients with reduced left ventricular function and ventricular enlargement after myocardial infarction are at significantly greater risk for congestive heart failure and death. Nevertheless, recovery of ventricular function occurs in a significant proportion of patients after myocardial infarction, and modern reperfusion strategies have been associated with increased recovery of function. OBJECTIVE: To determine the extent and predictors of recovery of ventricular function after anterior Q-wave myocardial infarction in the reperfusion era. DESIGN: Subgroup analysis of the Healing and Early Afterload Reducing Therapy study. SETTING: 35 medical centers in the United States and Canada. PATIENTS: 352 patients with Q-wave anterior myocardial infarction. INTERVENTION: Placebo for 14 days, followed by full-dose (10 mg) ramipril until day 90; low-dose (0.625 mg) ramipril for 90 days; or full-dose ramipril for 90 days. All patients underwent reperfusion therapy. MEASUREMENTS: Echocardiography was performed on day 1 (before randomization), day 14, and day 90 after myocardial infarction. Left ventricular volume and ejection fraction were measured and wall-motion analyses were performed at all three time points in 249 patients and at baseline in an additional 12 patients who died during follow-up. Echocardiographic and nonechocardiographic predictors of ventricular recovery were examined. RESULTS: By day 90, 55 of 252 (22%) patients who had abnormal ejection fraction and wall-motion abnormalities on day 1 demonstrated complete recovery of function (ejection fraction in the normal range and infarct segment length of 0%), and an additional 36% (91 of 252 patients) demonstrated partial recovery of function. At 90 days, 53% (132 of 249) of patients had greater than 5% improvement in ejection fraction, whereas only 16% (39 of 249) had a decrease in ejection fraction of more than 5%. The majority of functional improvement occurred by day 14 after infarction. Of various clinical and echocardiographic measures obtained on day 1, peak creatine kinase level was the strongest independent predictor of subsequent recovery of ventricular function in multivariate analysis. Each 100-unit increase in peak creatine kinase was associated with a 4.3% decreased odds of recovery (P < 0.001) after adjustment for ejection fraction on day 1, extent of akinesis or dyskinesis, treatment regimen, Killip class, age, and sex. CONCLUSION: Significant myocardial stunning with subsequent improvement of ventricular function occurred in the majority of patients after Q-wave anterior myocardial infarction. A lower peak level of creatine kinase, an estimate of the extent of necrosis, is independently predictive of recovery of function. Early functional assessment (day 1 after acute myocardial infarction) had limited ability to predict recovery of ventricular function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Statins: a brief summary.

Despite a totality of evidence indicating clear benefits of statin therapy in secondary and primary prevention of cardiovascular disease (CVD), a large number of additional trials are currently planned or in progress to help us better understand, treat, and prevent CVD. Both monotherapy and combination statin regimens are being studied to optimize treatment of the total patient and to assess mechanisms and benefits of various components of the total lipid profile.

Cardiovascular Diseases↗
PubMed2001

Regional wall stress predicts ventricular remodeling after anteroseptal myocardial infarction in the Healing and Early Afterload Reducing Trial (HEART): an echocardiography-based structural analysis.

BACKGROUND: Increased left ventricular (LV) wall stress after myocardial infarction (MI) has been implicated in LV remodeling. However, the relationship between LV wall stress and LV remodeling is incompletely defined. METHOD: We prospectively studied the relationship between regional wall stress and LV remodeling by application of the finite element method to end-systolic LV models from patients enrolled in the Healing and Early Afterload Reducing Therapy (HEART) Trial. Individual LV models were constructed from orthogonal apical echocardiographic views obtained at day 14 after anteroseptal MI in 64 patients. Of these, 31 patients received low-dose (0.625 mg) ramipril and 33 patients received full-dose (10 mg) ramipril. LV wall stress was calculated by the finite element method and correlated with change in LV volume from day 14 to day 90 after MI. RESULTS: Among all patients, increases in apical regional wall stress were associated with LV volume changes (P -trend =.015). The relationship between apical regional wall stress and change in LV volume was strongest in the low-dose ramipril group (r = 0.53, P =.002) and remained significant after adjustment for end-diastolic volume, infarct size, ejection fraction, and systolic blood pressure yet was attenuated in the full-dose ramipril group. CONCLUSIONS: Apical regional wall stress is an independent predictor of subsequent LV remodeling after MI. The relationship between increased apical wall stress and LV dilatation appears to be attenuated by full-dose angiotensin-converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Activation of cardiac c-Jun NH(2)-terminal kinases and p38-mitogen-activated protein kinases with abrupt changes in hemodynamic load.

The role of mitogen-activated protein kinase (MAPK) pathways as signal transduction intermediates of hemodynamic stress leading to cardiac hypertrophy in the adult heart is not fully established. In a rat model of pressure-overload hypertrophy, we examined whether activation of MAPK pathways, namely, the extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and the p38-MAPK pathways, occurs during rapid changes in hemodynamic load in vivo. A slight activation of ERK2 and marked increases in JNK1 and p38-MAPK activities were observed 30 minutes after aortic banding. The increase in p38-MAPK activity was accompanied by an increase in the phosphorylation of the p38 substrate MAPK-activated protein kinases 2 and 3. Activation of these kinases was coincident with an increase in phosphorylation of c-Jun and activating transcription factor-2 (ATF-2) and enhanced DNA binding of activator protein-1 factors. Thus, hemodynamic stress of the adult rat heart in vivo results in rapid activation of several parallel MAPK kinase cascades, particularly stress-activated MAPK and p38-MAPK and their target transcription factors c-Jun and ATF-2.

Activating Transcription Factor 2↗
PubMed2000

VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. METHODS AND RESULTS: We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL-apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P:=0.04), apoCIII in VLDL+LDL (RR 2.3, P:=0.04), and apoE in HDL (RR 1.8, P:=0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P:=0.03), was not related to coronary events (RR 1.3, P:=0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. CONCLUSIONS: The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.

Apolipoprotein C-III↗
PubMed2000

Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.

BACKGROUND: We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome. METHODS: We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure. FINDINGS: Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included. INTERPRETATION: Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.

Angiotensin II↗
PubMed2000

Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.

BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

Aged↗
PubMed2000

Endothelin-A receptor antagonism during acute myocardial infarction in rats.

Endothelin levels are increased in rats with experimentally induced myocardial infarction. The purpose of this study was to determine whether endothelin-A (ET(A)) receptor antagonism alters ventricular remodeling and the development of heart failure after myocardial infarction (MI). We administered 10 mg/kg/day of A-127722 to rats post-MI for 6 weeks. A hemodynamic study was performed and passive pressure-volume curves obtained. In rats without infarcts, ET(A) receptor antagonist (n = 8; vehicle, n = 5) had no effect. However, in rats with infarcts ET(A) antagonism (n=14, MI = 35%; vehicle: n = 19, MI = 32%) reduced systemic arterial and LV systolic (but not end-diastolic) pressures and shifted the pressure-volume relationship to the right. Because LV mass was not changed, the volume-to-mass ratio was increased and was correlated inversely with the ability of the LV to maximally develop pressure. This increase in volume at low distending pressures was also coupled with a tendency (P < 0.06) for reduced scar thickness, suggesting that early initiation of an ET(A) receptor antagonism increased infarct expansion. The reduction in blood pressure offset the increase in volume such that wall stresses were unchanged, as was LV mass. The early use of ET(A) receptor antagonism in the rat model of myocardial infarction did not beneficially alter LV remodeling.

Animals↗
PubMed2000

Enhancing cardiac protection after myocardial infarction: rationale for newer clinical trials of angiotensin receptor blockers.

Treatment of acute myocardial infarction (MI) has been advanced considerably in the past 20 years with the advent of acute reperfusion strategies such as thrombolytic therapy or primary angioplasty and the use of adjunctive medical therapies such as aspirin, beta-blockers, and HMG-CoA reductase inhibitors (statins); each has been proven to reduce morbidity and mortality rates after MI. Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in this list of winners, particularly in patients clinically assessed as being at higher risk for cardiovascular death. The benefits of treating such patients with an ACE inhibitor have clearly shown significant improvements in survival that are both complementary and additive to the other proven therapies. However, a significant subset of patients treated with ACE inhibitors will die or have worsening congestive heart failure despite adequate therapy. Appropriate risk stratification can help guide the clinician in identifying patients at greatest risk for cardiovascular events after MI. Fortunately, investigators are currently exploring the potential benefits of more specific and selective blockade of the renin-angiotensin system with AT(1) receptor blockers (ARBs) in the hope of enhancing survival beyond that evidenced with ACE inhibition alone. These agents pharmacologically inhibit the renin-angiotensin system at the angiotensin (Ang) II type 1 receptor level. Although there are theories postulating why blocking the harmful effects of Ang II at this receptor would be more effective than inhibiting ACE-mediated conversion from inactive Ang I to Ang II, extrapolation to the clinical setting remains highly speculative. These hypotheses can only be tested by direct comparisons of ACE inhibitors and ARBs in the appropriate patient populations. The VALIANT (Valsartan in Acute Myocardial Infarction) trial is testing the hypothesis that interruption of the renin-angiotensin pathway by using the ARB valsartan alone or in combination with an ACE inhibitor will be more effective in saving lives than an ACE inhibitor alone in treating patients at high risk. This trial will enroll patients with symptoms of congestive heart failure or depressed left ventricular ejection fraction and randomly assign them to either captopril, valsartan, or the combination. Other proven conventional post-MI therapies are encouraged. This study will definitively determine whether the use of valsartan offers additional benefits over those achieved with ACE inhibitor monotherapy in patients at high risk after MI.

Angiotensin II↗
PubMed2000

Valsartan in acute myocardial infarction trial (VALIANT): rationale and design.

BACKGROUND: Survivors of acute myocardial infarction (MI) complicated by heart failure and/or resulting in left ventricular dysfunction are at heightened risk for subsequent death and major nonfatal cardiovascular events. Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor has consistently been demonstrated to result in reductions in these risks by approximately 20%. The development of angiotensin II receptor blockers offers a new, more specific, and theoretically more complete pharmacologic mode to inhibit the adverse influence of angiotensin II. METHODS: Valsartan in Acute Myocardial Infarction (VALIANT) is a multicenter, double-blind, randomized, active controlled parallel group study comparing the efficacy and safety of long-term treatment with valsartan, captopril, and their combination in high-risk patients after MI. The trial is designed with 3 arms, giving equal statistical consideration to survival comparisons of captopril versus the angiotensin II receptor blocker valsartan, as well as the combination of captopril plus valsartan, compared with a proven effective dose of captopril. This 14,500-patient trial is designed with an 86% power to detect a 15% reduction in mortality rate with either use of valsartan compared with captopril. The trial encourages optimal individualization of other proven therapies in acute and chronic infarction, and the international patient body ensures good representation of multiple practice patterns. CONCLUSION: VALIANT is a large international investigative effort that will evaluate the role of valsartan in the management of patients with MI associated with heart failure and/or left ventricular dysfunction. The use of a proven dose of captopril and the comparator arms with valsartan alone or in combination with captopril provides a unique test of whether the angiotensin II receptor blocker can make an additional improvement in clinical outcomes beyond angiotensin-converting enzyme inhibitors.

Angiotensin II↗
PubMed1999

Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators.

BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that reduces cardiovascular risk, might alter levels of this inflammatory parameter. METHODS AND RESULTS: CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated (r=0.60, P<0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, +4. 2%; P=0.2 and mean change, +0.07 mg/dL; P=0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, -17.4%; P=0.004 and mean change, -0.07 mg/dL; P=0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, -21.6%; P=0.007), mean CRP levels (difference, -37.8%; P=0.002), and absolute mean change in CRP (difference, -0.137 mg/dL; P=0.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. CONCLUSIONS: Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.

Adult↗
PubMed1999

Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction. BACKGROUND: Increased conduit vessel stiffness increases pulse pressure and pulsatile load, potentially contributing to adverse outcomes in patients with left ventricular dysfunction. METHODS: Pulse and mean arterial pressure were analyzed for their effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 6,781 patients randomized into the Studies of Left Ventricular Dysfunction trials. RESULTS: Pulse and mean arterial pressure were related positively to each other, age, ejection fraction and prevalence of diabetes and hypertension and inversely to prior myocardial infarction and beta-adrenergic blocking agent use. Higher pulse pressure was associated with increased prevalence of female gender, greater calcium channel blocking agent, digoxin and diuretic use, lower heart rate and a higher rate of reported smoking history. Higher mean arterial pressure was associated with higher heart rate, lower calcium channel blocker and digoxin use and lower New York Heart Association functional class. Over a 61-month follow-up 1,582 deaths (1,397 cardiovascular) occurred. In a multivariate analysis adjusting for the above covariates and treatment assignment, higher pulse pressure remained an independent predictor of total and cardiovascular mortality (total mortality relative risk, 1.05 per 10 mm Hg increment; 95% confidence interval, 1.01 to 1.10; p = 0.02). Mean arterial pressure was inversely related to total and cardiovascular mortality (total mortality relative risk, 0.89; 95% confidence interval, 0.85 to 0.94; p <0.0001). CONCLUSIONS: One noninvasive blood pressure measurement provides two independent prognostic factors for survival. Increased conduit vessel stiffness, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure.

Adult↗
PubMed1999

Increased pulse pressure and risk of heart failure in the elderly.

CONTEXT: Arterial stiffness increases with age. Thus, pulse pressure, an index of arterial stiffening, may predict congestive heart failure (CHF) in the elderly. OBJECTIVE: To study prospectively the association between pulse pressure and risk of CHF. DESIGN: Prospective cohort study. SETTING: The community-based East Boston Senior Health Project, East Boston, Mass. PATIENTS: A total of 1621 men and women (mean [SD] age, 77.9 [5.0] years) free of CHF who had blood pressure measurements taken in 1988-1989 and were followed up for 3.8 years. MAIN OUTCOME MEASURE: Incidence of CHF as ascertained by hospital discharge diagnosis (n = 208) and death certificates (n = 13). RESULTS: After controlling for age, sex, mean arterial pressure, history of coronary heart disease, diabetes mellitus, atrial fibrillation, valvular heart disease, and antihypertensive medication use, pulse pressure was an independent predictor of CHF. For each 10-mm Hg elevation in pulse pressure, there was a 14% increase in risk of CHF (95% confidence interval, 1.05-1.24; P = .003). Those in the highest tertile of pulse pressure (>67 mm Hg) had a 55% increased risk of CHF (P=.02) compared with those in the lowest (<54 mm Hg). Pulse pressure was more predictive than systolic blood pressure alone and was independent of diastolic blood pressure. CONCLUSION: Pulse pressure, an easily measurable correlate of pulsatile hemodynamic load, is an independent predictor of risk of CHF in this elderly cohort.

Aged↗
PubMed1999

Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators.

BACKGROUND: The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. METHODS AND RESULTS: To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, pravastatin lowered total serum cholesterol by 20%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P=0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P=0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 versus 6, respectively). CONCLUSIONS: Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infarction in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy.

Aged↗
PubMed1999

Influence of baseline lipids on effectiveness of pravastatin in the CARE Trial. Cholesterol And Recurrent Events.

OBJECTIVES: We sought to assess the influence of baseline lipid levels on coronary event rates and the effectiveness of pravastatin therapy in the Cholesterol And Recurrent Events (CARE) study. BACKGROUND: The CARE study cohort provided a relatively unique opportunity to examine the relation between lipid levels and clinical events in a post-myocardial infarction (MI) population with relatively low cholesterol and low density lipoprotein (LDL) cholesterol values. METHODS: There were 4,159 patients with a previous infarct and a total cholesterol level <240 mg/dl, LDL cholesterol level 115 to 174 mg/dl and triglyceride level <350 mg/dl randomly allocated to placebo (n=2,078) or pravastatin 40 mg/day (n=2,081). Time to either coronary death or nonfatal MI (primary end point) or to the secondary end point, which included undergoing a coronary revascularization procedure, was determined as a function of baseline lipids (total, LDL, high density lipoprotein [HDL] cholesterol and triglyceride levels). RESULTS: Quartile analysis indicated important effects for LDL cholesterol, in which a higher LDL was associated with greater cardiac event rates (in the placebo group, every 25-mg/dl increment in LDL was associated with a 28% increased risk [5% to 56%, p=0.015]) in the primary event. The differential event rates with respect to baseline LDL cholesterol for placebo and pravastatin groups reduced the difference in clinical outcomes at lower LDL cholesterol levels. In both the placebo and pravastatin groups, an inverse relation between baseline HDL cholesterol and cardiac events was observed (10 mg/dl lower baseline HDL cholesterol level was associated with a 10% [0% to 19%, p=0.046] increase in coronary death or nonfatal MI). CONCLUSIONS: Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.

Adult↗
PubMed1999

Ejection fraction by radionuclide ventriculography and contrast left ventriculogram. A tale of two techniques. SAVE Investigators. Survival and Ventricular Enlargement.

OBJECTIVES: We assessed the abilities of two methods to measure ejection fraction (EF)-radionuclide ventriculography (RVG) and contrast left ventriculography (Cath-EFa) to predict cardiovascular events. BACKGROUND: Both RVG and Cath-EFa are commonly used methods to measure left ventricular performance and assess prognosis. Their comparative abilities to predict clinical events have not been reported. METHODS: Both RVG EF and Cath-EFa were measured within 16 days of myocardial infarction (MI) in 688 patients. The results were divided into terciles. Prognosis by terciles was assessed for each technique. A multivariate analysis was performed to determine which EF measurement was a better predictor of prognosis. RESULTS: Average RVG-EF was 32%+/-7, while Cath-EFa was 42%+/-10. Both RVG and Cath-EFa were poorly correlated (R=0.42). Event rate declined across terciles with increasing EF for both techniques (events in lowest to highest tercile of Cath-EFa 40.7%, 25.9%, 11.6%, p < 0.001; and RVG-EF 39.9%, 26.1%, 15.6%, p < 0.001). There was concordance of terciles in 303 of 688 patients (44%). When patients in the highest RVG terciles were in the highest Cath-EFa tercile, the event rate was 7%. However, when patients in the highest RVG terciles were in the lowest Cath-EFa tercile, the event rate was 19%. Both Cath-EFa (p < 0.001) and RVG-EF (p < 0.001) were independent predictors of cardiovascular events. CONCLUSIONS: Ejection fraction measured by RVG or during catheterization is a valuable tool in the risk stratification of postinfarct patients. When disagreement is present between clinical impression and measurement by either method, the use of an alternative measurement is warranted and complementary.

Adult↗