Showing papers by "Marc A. Pfeffer published in 2011"
TL;DR: The TOPCAT trial is designed to assess definitively the role of spironolactone in the management of HF-PEF, and key secondary end points include quality of life, nonfatal cardiovascular events, and new-onset atrial fibrillation.
247 citations
TL;DR: There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls, and there was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.
Abstract: Background Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks.Objective Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants.Patients and methods Individuals at high CVD risk were randomized to telmisartan (three trials, n=51 878), irbesartan (three trials, n=14 859), valsartan (four trials, n=44 264), candesartan (four trials, n=18 566), and losartan (one trial, n=9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n=42 403), the ARBs were compared to ACEi and in 11 trials (n=63 313) to controls without ACEi. In addition, in seven trials (n=47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n=25 712).Results Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [ 4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.Conclusion There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.
182 citations
TL;DR: The CKD-EPI equation provides more accurate risk stratification than the MDRD Study equation in patients at high risk for CV disease, including identification of increased risk at mildly decreased eGFR.
160 citations
TL;DR: Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.
Abstract: Background—Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. Methods and Results—In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty...
155 citations
TL;DR: Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity and can provide a useful alternative perspective on the effects of treatment in future HF trials.
139 citations
TL;DR: Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects.
Abstract: Aims Direct renin inhibitors provide an alternative approach to inhibiting the renin–angiotensin–aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS.
Methods and results We randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren ( n = 423), titrated to 300 mg, or matched placebo ( n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26–36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (−4.4 ± 16.8 mL) or placebo (−3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia.
Conclusion Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.
Clinical Trials Registration: [www.clinicaltrials.gov][1] [NCT00414609][2]
[1]: http://www.clinicaltrials.gov
[2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00414609&atom=%2Fehj%2Fearly%2F2011%2F02%2F10%2Feurheartj.ehq522.atom
134 citations
TL;DR: Measurement of troponin T and NT-pro-BNP may improve the identification of patients with CKD who are likely to require renal replacement therapy, supporting a link between cardiac injury and the development of ESRD.
131 citations
TL;DR: The growth properties of mC SCs and vCSCs isolated from endomyocardial biopsies from patients with advanced heart failure were comparable to those obtained previously from larger myocardial samples of patients undergoing elective cardiac surgery.
Abstract: Rationale: Two categories of cardiac stem cells (CSCs) with predominantly myogenic (mCSC) and vasculogenic (vCSC) properties have been characterized in the human heart. However, it is unknown whether functionally competent CSCs of both classes are present in the myocardium of patients affected by end-stage cardiac failure, and whether these cells can be harvested from relatively small myocardial samples. Objective: To establish whether a clinically relevant number of mCSCs and vCSCs can be isolated and expanded from endomyocardial biopsies of patients undergoing cardiac transplantation or left ventricular assist device implantation. Methods and Results: Endomyocardial biopsies were collected with a bioptome from the right side of the septum of explanted hearts or the apical LV core at the time of left ventricular assist device implantation. Two to 5 biopsies from each patient were enzymatically dissociated, and, after expansion, cells were sorted for c-kit (mCSCs) or c-kit and KDR (vCSCs) and characterized. mCSCs and vCSCs constituted 97% and 3% of the c-kit population, respectively. Population doubling time averaged 27 hours in mCSCs and vCSCs; 5×10 6 mCSCs and vCSCs were obtained in 28 and 41 days, respectively. Both CSC classes possessed significant growth reserve as documented by high telomerase activity and relatively long telomeres. mCSCs formed mostly cardiomyocytes, and vCSCs endothelial and smooth muscle cells. Conclusions: The growth properties of mCSCs and vCSCs isolated from endomyocardial biopsies from patients with advanced heart failure were comparable to those obtained previously from larger myocardial samples of patients undergoing elective cardiac surgery.
121 citations
TL;DR: Cardiac resynchronization therapy resulted in a significant improvement in both LV dyssynchrony and contractile function measured by GLS compared with ICD only and these improvements were associated with better subsequent outcomes.
Abstract: To assess long-term effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) dyssynchrony and contractile function, by two-dimensional speckle-tracking echocardiography, compared with implantable cardioverter defibrillator (ICD) only in MADIT-CRT.
99 citations
TL;DR: Recurrent myocardial infarction is common after a first MI and is associated with increased morbidity and mortality and predictors and prognosis with contemporary management are not well known.
Abstract: Aims
Recurrent myocardial infarction (MI) is common after a first MI and is associated with increased morbidity and mortality. Predictors and prognosis of a recurrent MI with contemporary management are not well known.
Methods and results
We assessed the predictors and prognostic impact of a first recurrent MI in 10 599 patients with left ventricular dysfunction, heart failure, or both following a first MI from the Valsartan in Acute Myocardial Infarction Trial (VALIANT) cohort. During a median follow-up of 27.4 months, 861 patients (9.6%) had a recurrent MI. The median time to recurrence was 136 days (quartiles 35–361 days), with a declining rate of recurrent MI within the first 3 months. The strongest predictors of recurrent MI were reduced estimated glomerular filtration rate, unstable angina, diabetes, and age. Mortality was markedly elevated (20.5%) within the first 7 days of a recurrent MI. Patients who survived 7 days after a recurrent MI continued to be at increased risk of death compared with patients without a recurrent MI and the risk of death remained elevated more than two-fold a year after the recurrent MI (adjusted hazards ratio 2.4, 95% confidence interval 1.7–3.2). One-year mortality for the entire VALIANT cohort was 10.3%, whereas 38.3% of the patients were dead 1 year after recurrent MI. Early reinfarctions (within 1 month) was associated with significantly higher 30-day mortality than later reinfarctions.
Conclusion
Even in the context of contemporary treatment, a recurrent MI confers a significantly increased risk of death in patients following a high-risk first MI. Strategies aimed at reducing recurrent MI will thus likely prolong survival in post-MI survivors.
83 citations
TL;DR: Both mechanical dyssynchrony and contractile function are important independent correlates of benefit from CRT, and both predicted response to CRT independent of each other, QRS width, LV ejection fraction, and presence versus absence of left bundle-branch block.
Abstract: Background—Despite benefits of cardiac resynchronization therapy (CRT) in patients with severe but less symptomatic heart failure, approximately 30% of patients do not fully respond to treatment. W...
TL;DR: In this paper, a multivariate logistic regression model was used to identify baseline predictors of stroke in 4038 patients with diabetes mellitus, chronic kidney disease, and anemia randomized to receive darbepoetin alfa or placebo.
Abstract: Background—More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association. Methods and Results—A multivariate logistic regression model was used to identify baseline predictors of stroke in 4038 patients with diabetes mellitus, chronic kidney disease, and anemia randomized to receive darbepoetin alfa or placebo. To determine whether postrandomization blood pressure, hemoglobin level, platelet count, or treatment dose were responsible for the increased risk related to darbepoetin alfa, we performed a nested case-control analysis (1:10 matching) identifying nonstroke controls with propensity matching. The risk of stroke was doubled with darbepoetin alfa. Overall, 154 patients had a stroke, 101/2012 (5.0%) in the darbepoetin alfa arm and 53/2026 (2.6%) in the placebo arm (hazard ratio 1.9; 95% confidence interval, 1...
University of Glasgow1, Brigham and Women's Hospital2, Harvard University3, University of Groningen4, University of Erlangen-Nuremberg5, Northwestern University6, Tufts University7, Washington University in St. Louis8, St. John's University9, University of Copenhagen10, University of Texas Southwestern Medical Center11
TL;DR: In this article, the authors examined predictors of cardiovascular mortality and morbidity in patients with chronic kidney disease (CKD) and found that individuals with the triad of diabetes, CKD, and anemia represent a significant proportion of patients with cardiovascular disease and are at particularly high risk for adverse outcomes.
TL;DR: In this article, the longitudinal impact of anemia treatment on quality of life (QOL) in patients with diabetes and chronic kidney disease was investigated. But, the authors did not identify the predictors of baseline and change in QOL.
Abstract: Summary Background and objectives Quality of life (QOL) is markedly impaired in patients with anemia, diabetes mellitus, and chronic kidney disease. Limited data exist regarding the effect of anemia treatment on patient perceptions. The objectives were to determine the longitudinal impact of anemia treatment on quality of life in patients with diabetes and chronic kidney disease and to determine the predictors of baseline and change in QOL. Design, setting, participants, & measurements In a large, double blind study, patients with type 2 diabetes mellitus, nondialysis chronic kidney disease (estimated GFR, 20 to 60 ml/min per 1.73 m 2 ), and anemia (hemoglobin 10.4 g/dl) were randomized to darbepoetin alfa or placebo. QOL was measured with Functional Assessment of Cancer Therapy-Fatigue, Short Form-36, and EuroQol scores over 97 weeks. Results Patients randomized to darbepoetin alfa reported significant improvements compared with placebo patients in Functional Assessment of Cancer Therapy-Fatigue, and EuroQol scores visual analog scores, persisting through 97 weeks. No consistent differences in Short Form-36 were noted. Consistent predictors of worse change scores include lower activity level, older age, pulmonary disease, and duration of diabetes. Interim stroke had a substantial negative impact on fatigue and physical function. Conclusion Darbepoetin alfa confers a consistent, but small, improvement in fatigue and overall quality of life but not in other domains. These modest QOL benefits must be considered in the context of neutral overall effect and increased risk of stroke in a small proportion of patients. Patient’s QOL and potential treatment risk should be considered in any treatment decision. Clin J Am Soc Nephrol 6: 845–855, 2011. doi: 10.2215/CJN.06450710
TL;DR: Findings suggest greater baseline concentric remodeling and long-term elevation in LV diastolic pressure post-MI among diabetic patients, which may partially mediate this risk of death or HF.
01 Jan 2011
TL;DR: The results of longitudinal studies showed that the areas, where positive ticks could be repeatedly detected, were relatively small in comparison to earlier descriptions, implying that the natural circulation of TBEV between ticks and rodents or other small mammals occurs in rather small areas, named microfoci.
Abstract: Ticks transmit a number of pathogens to humans and animals. Among them, the most important arboviral human disease in Central Europe and Northern Asia is tick-borne encephalitis (TBE). The Western subtype of TBE virus (TBEV) in Central Europe is mainly transmitted by the tick Ixodes ricinus. The incidence and the numbers of human cases are thought to be correlated to tick activity. Two different, but closely located TBEV endemic foci in South Eastern Germany were studied. The results of our longitudinal studies in both foci showed that the areas, where positive ticks could be repeatedly detected, were relatively small in comparison to earlier descriptions. The data of two endemic foci of TBEV imply that the natural circulation of TBEV between ticks and rodents or other small mammals occurs in rather small areas, named microfoci. From these microfoci, TBEV-bearing ticks are dispersed eventually, probably by larger forest animals with a greater radius of activity than rodents. Human infection occurs if humans enter the microfocus area or if infected ticks are dispersed and occasionally come into contact with humans, for example in gardens near forests or on forest ways within the area of activity of the larger forest animals, named macrofocus or endemic area. Further studies are needed to show whether this concept of TBEV microfocus and TBEV macrofocus will also apply to other endemic areas such as for example in Southwestern Germany.
TL;DR: In the recent Matrixx case, the Supreme Court decided that drug-company investors require increased access to statistically nonsignificant information regarding adverse drug experiences and that Prescribers' access to the same level of information should also be increased.
Abstract: In the recent Matrixx case, the Supreme Court decided that drug-company investors require increased access to statistically nonsignificant information regarding adverse drug experiences. Prescribers' access to the same level of information should also be increased.
TL;DR: Predictors of death and development of heart failure were assessed in 603 patients from the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiographic substudy, finding that measures of cardiac structure and function beyond LVEF provide important prognostic information beyond the clinical assessment.
TL;DR: It is suggested that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking β blockers, and this risk was decreased in patients treated concurrently with an ACE inhibitor.
Abstract: We used data from patients with stable coronary artery disease (CAD) to assess the risk of new-onset diabetes mellitus (NOD) with β blockers and to determine whether angiotensin-converting enzyme (ACE) inhibition would modify this risk. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial randomized 8,290 patients with stable CAD to trandolapril or placebo. Presence of NOD was assessed at each study visit over a median follow-up time of 4.8 years. We examined the risk of NOD associated with β-blocker use with Cox regression models adjusting for 25 baseline covariates and tested whether this risk was modified by randomization to the ACE inhibitor. Of 6,910 patients without diabetes mellitus at enrollment (1,179 women and 5,731 men, mean age 64 ± 8 years), 4,147 (60%) were taking β blockers and 733 (8.8%) developed NOD. We observed a significant interaction between β-blocker use and randomization to ACE inhibitor with respect to NOD (p = 0.028). Participants taking β blockers assigned to the placebo group (n = 2,090) were at increased risk for NOD adjusting for baseline covariates (hazard ratio 1.63, 95% confidence interval 1.29 to 2.05, p
TL;DR: A high proportion of SD events after high-risk myocardial infarction occurred at home, but in-hospital events were more common early on.
Abstract: Background—Sudden death (SD) is a frequent catastrophic complication in patients after myocardial infarction. Circumstances of SD may affect strategies for prevention. Methods and Results—We reviewed source documentation for 1067 patients who had SD in the Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial. We determined the circumstances of these events and assessed long-term mortality in patients who were resuscitated. Location of the SD event was available in 978 of 1067 patients, with 226 events occurring within the first 40 days. Although SD was more likely to occur at home (645 of 978, 66%) than in hospital (204 of 978, 21%), the proportion of in-hospital events was higher early on (99 of 226, 44%). Home events were less likely to be witnessed regardless of time frame. Preceding activity was known for 42% of patients with home arrest; of these, 52% were determined to be asleep at time of event, and these deaths were more likely to be unwitnessed. A majority of patients for whom initial E...
TL;DR: The availability of HmG CoA reductase inhibitors changed the approach to cholesterol management, because these drugs were well tolerated and caused marked reductions in total cholesterol (TC) and LDL-C in the majority of individuals.
Abstract: Featured Article: Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001–9.4
In 1984, a National Heart, Lung and Blood Institute trial demonstrated that reducing LDL cholesterol (LDL-C)5 with a combination of diet and large doses of the cholesterol-binding resin cholestyramine reduced coronary events (1) and slowed the progression of coronary artery obstruction (2) in men with increased cholesterol concentrations. Resins were not well tolerated, however, and patient compliance was poor. Subsequently, the availability of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HmG CoA) reductase inhibitors changed the approach to cholesterol management, because these drugs were well tolerated and caused marked reductions in total cholesterol (TC) and LDL-C in the majority of individuals.
Two important clinical-outcome trials were launched promptly for patients with hypercholesterolemia. The Scandinavian Simvastatin Survival Study (3) enrolled patients with coronary artery disease and hypercholesterolemia [average TC, 261 mg/dL (6.6 mmol/L); average LDL-C, 188 mg/dL (4.87 mmol/L)], and the West of Scotland Coronary Prevention Study (4) used pravastatin in men without clinical coronary disease [average TC, 272 mg/dL (7.0 mmol/L); average LDL-C, 192 mg/dL (5.0 mmol/L)].
On the basis of the earlier findings (1, 2), we assumed that these trials would show clinical benefit; however, patients with the …
Journal Article•
TL;DR: Patients with heart failure and reduced ejection fraction (HF-REF) are at increased risk of stroke, with some studies suggesting an inverse association between ejectION fraction (EF) and...
Abstract: Objectives Patients with heart failure and reduced ejection fraction (HF-REF) are at increased risk of stroke, with some studies suggesting an inverse association between ejection fraction (EF) and...
01 Jan 2011
TL;DR: These trials did not show a benefit of early implantable cardioverter-defibrillator (ICD) implantation after MI in patients with low ejection fraction, and concluded that, although ICD therapy was associated with a reduction in the rate of arrhythmic death, high rates of cardiac mortality in the ICD group were from mechanisms other than tachyarrhythmia.
Abstract: We thank Dr McEvoy for his interest in our article.1 Despite an increased risk of sudden death in the first weeks after myocardial infarction (MI), a retrospective analysis of Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II),2 the prospective randomized Defibrillator in Acute Myocardial Infarction (DINAMIT),3 and the Immediate Risk Stratification Improves Survival (IRIS)4 trials did not show a benefit of early implantable cardioverter-defibrillator (ICD) implantation after MI in patients with low ejection fraction. As pointed out by Dr McEvoy, the DINAMIT and IRIS trials also concluded that, although ICD therapy was associated with a reduction in the rate of arrhythmic death that was offset by an increase in the rate of nonarrhythmic death, high rates of cardiac mortality in the ICD group were from mechanisms other than tachyarrhythmia. Because the results of these trials were neutral, it is important to …