Author
Marc A. Pfeffer
Other affiliations: Partners HealthCare, University of Miami, Mount Sinai Hospital ...read more
Bio: Marc A. Pfeffer is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Heart failure & Myocardial infarction. The author has an hindex of 166, co-authored 765 publications receiving 133043 citations. Previous affiliations of Marc A. Pfeffer include Partners HealthCare & University of Miami.
Papers published on a yearly basis
Papers
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54 citations
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TL;DR: Use of spironolactone is supported to treat HFpEF patients with advanced chronic kidney disease only when close laboratory surveillance is possible, and the risk of AEs was amplified in the lower eGFR categories.
Abstract: Objectives This study investigated the association between baseline renal function and the net benefit of spironolactone in patients with heart failure (HF) with a preserved ejection fraction (HFpEF). Background Guidelines recommend consideration of spironolactone to reduce HF hospitalization in HFpEF. However, spironolactone may increase risk for hyperkalemia and worsening renal function, particularly in patients with chronic kidney disease. Methods This investigation analyzed data from patients enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) Americas study (N = 1,767) to examine the association between the baseline estimated glomerular filtration rate (eGFR) and the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest, as well as safety outcomes, including hyperkalemia, worsening renal function, and permanent drug discontinuation for adverse events (AEs). Variations in the efficacy and safety of spironolactone according to eGFR were examined in Cox models using interaction terms. Results The incidence of both the primary outcome and drug-related AEs increased with declining eGFR. Compared with placebo, across all eGFR categories, spironolactone was associated with lower relative risk for the primary efficacy outcome and for hypokalemia, but higher relative risk for hyperkalemia, worsening renal function, and drug discontinuation. During 4-year follow-up, the absolute risk for AEs that prompted drug discontinuation was amplified in the lower eGFR categories, which suggested heightened risk for drug intolerance with declining renal function. Conclusions Although consistent efficacy of spironolactone was observed across the range of eGFR, the risk of AEs was amplified in the lower eGFR categories. These data supported use of spironolactone to treat HFpEF patients with advanced chronic kidney disease only when close laboratory surveillance is possible.
54 citations
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TL;DR: Three methods of estimating characteristic impedance from the impedance spectra were evaluated and found to produce comparable results at baseline and following pharmacological elevation of blood pressure with graded methoxamine infusion.
Abstract: Measurement of aortic input impedance in the rat is complicated by a high basal heart rate but is possible if appropriate compensation is made for frequency-dependent errors in modulus and phase resulting from analog filters in the equipment and from nonalignment of pressure and flow sensors. Because input impedance is a complex quantity, accurate values for both phase and modulus are required before meaningful interpretation of the data can be made. We measured aortic pressure and electromagnetic ascending aortic blood flow in mature, ether-anesthetized, open-chest male Wistar rats. Pressure and flow waveforms were averaged in the time domain and converted to Fourier series. Flow moduli were corrected for the measured frequency response of the flowmeter. Phase spectra were corrected by the classic frequency-domain and two new time-domain methods. Compensation for instrumentation errors was assessed at two different flowmeter filter settings in five animals. Reproducibility, variability, and the effects of vasoconstriction were assessed in 43 animals. Three methods of estimating characteristic impedance from the impedance spectra were evaluated and found to produce comparable results at baseline and following pharmacological elevation of blood pressure with graded methoxamine infusion. Physiologically equivalent values for phase, as assessed by comparing oscillatory power calculated from the impedance spectra, were obtained with each of the phase-correction techniques. The new time-domain methods facilitate the assessment of aortic input impedance in this small animal model because they do not require measurement of the spatial separation between pressure and flow transducers and pulse wave velocity in the proximal aorta.
54 citations
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TL;DR: Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint.
Abstract: Aims
Hospitalization for worsening heart failure (HF) is known to increase mortality and morbidity risk and has been frequently used as an endpoint in randomized clinical trials. Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint.
Methods and results
MADIT-CRT randomized patients with mild HF symptoms to resynchronization therapy vs. control with an average follow-up of 3.3 years and a total of 191 deaths. HF events were centrally adjudicated for receiving i.v. decongestive therapy in an outpatient setting, or an augmented HF regimen during a hospital stay. Patients were compared according to whether their first HF was an out- or inpatient event. The first primary event was non-fatal outpatient HF, non-fatal inpatient HF, and death in 52, 331, and 78 patients, respectively. Patients with inpatient HF tended to be older and more likely to have HF of ischaemic aetiology than subjects who developed outpatient HF events. The risk of death following either type of non-fatal HF events was extremely high [hazard ratio (HR) 12.4, 95% confidence interval (CI) 9.1–16.9 for inpatient HF; HR 10.7, 95% CI 6.1–18.7 for outpatient HF] compared with subjects without non-fatal HF events. Allocation to CRT-D was associated with significant reduction in both types of HF.
Conclusion
Outpatient management of worsening HF portends a high risk of death, similar to inpatient HF events, and may be equally sensitive to the effects of therapy. These findings suggest that outpatient HF events should be considered in publicly reported outcomes measures and future HF clinical trials.
Trial Registration
NCT01294449.
54 citations
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TL;DR: To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and whether the reduction inalbuminuria was too small to afford clinical benefit, a large number of patients were enrolled.
Abstract: Aims:
In the ALTITUDE trial, direct renin inhibition with aliskiren on top of ACEi_or_ARB therapy decreased albuminuria by 14% while this did not lead to cardiorenal protection. Prior studies have demonstrated that the renoprotective effect of single RAAS blockade is associated with approximately 30% albuminuria reduction. . We therefore firstly investigated whether the degree of albuminuria reduction is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria in ALTITUDE was too small to afford clinical benefit.
Methods:
In a post-hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of month-6 albuminuria changes on renal and cardiovascular outcomes by Cox proportional_hazard_regression.
Results:
The median change in albuminuria in the first 6 months in the aliskiren group was -12%( 25th to 75th Percentile: -48.7_to_+41.9%) and 0.0[-40.2_to_55%] in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: >30% reduction in albuminuria in the first 6 months was associated with 62% renal and 25% cardiovascular risk reduction compared to an increase in albuminuria. The association between month-6 changes in albuminuria and renal or cardiovascular endpoints was similar in both treatment groups (p for interaction >0.1 for both endpoints).
Conclusions:
Addition of aliskiren to ACEi/ARB therapy shows albuminuria changes that are associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection since the overall albuminuria reduction in the aliskiren arm was too small and nearly similar to placebo.
53 citations
Cited by
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Boston University1, Rush University Medical Center2, University of Tennessee Health Science Center3, University of Michigan4, University at Buffalo5, University of Mississippi6, University of Miami7, University of Alabama at Birmingham8, Case Western Reserve University9, National Institutes of Health10
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.
24,988 citations
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23 Sep 2019TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
21,235 citations
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
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TL;DR: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.
Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...
18,691 citations
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TL;DR: Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups.
Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.
17,213 citations