eGFR has replaced true measured GFR in most nephrologists learned minds...
We are told in epidemiological studies that those with eGFR higher than 100 ml/min have a higher mortality....
We are told at ASN 2015 that those whose with CKD eGFR improves by >3ml/min/year have higher mortality...
We equate higher eGFR to "Hyperfiltration"... a concept that was debatable in rats...but fully accepted without a shred of evidence in humans...
We are told, and most believe, so many things in the name and at the altar of eGFR: estimated GFR....when in reality it is NEITHER ESTIMATED NOR MEASURED...it is simply calculated based on dubious, totally unecessary and misleading equations that PRETEND TO REFLECT TRUE AND MEASURED GFR...!!!
Therefore eGFR = iGFR: ILLUSION OF GFR...
As it is mostly:
in most general population studies:
and it is totaly unrepresentative of TRUE GFR in those who have advanced CKD4-5. Where tubular secretion of creatinine makes up to 40-50% of the urinary excretion of creatinine.
BUT MORE, SIGNIFICANTLY, eGFR IS THE MIRROR IMAGE OF SERUM CREATININE THAT FALLS WITH ILLNESS, ANOREXIA, MUSCLE WATING SARCOPENIA AND MALNUTRITION...SO:
of course those with high eGFR have higher mortality...they are wasted...
of course those with rising eGFR have worse prognosis and mortality...they are wasted....
of course those starting RRT/dialysis at higher eGFR are worse off...they are wasted...
NOTHING TO DO WITH TRUE GFR JUST AN ILLUSION...OF GFR:
REPORTING FROM ASN 2014, PROF PIERRE DELANAYE:
La sclérostine est considérée comme un nouveau biomarqueur intéressant dans le cadre de la « santé osseuse ». La sclérostine est produite par les ostéocytes en réponse à différents stimuli dont les plus importants sont la PTH et le stress mécanique. En l’absence de stress mécanique (l’exemple le plus illustratif étant celui des astronautes en apesanteur), l’ostéocyte va produire de la sclérostine qui va elle inhiber la fonction ostéoblastique via un effet sur la voie Wnt-cathénine.
Certains points nouveaux ont été soulignés à l’ASN.
Il existe bien une corrélation entre l’expression de la sclérostine au niveau osseux par les ostéocytes et la concentration plasmatique de sclérostine. La sclérostine aurait aussi un effet autocrine sur la production de RANKL (et donc l’activité ostéoclastique). L’ostéocyte pourrait également interagir au niveau de la fonction musculaire. En cas de maladie rénale chronique (MRC), l’expression osseuse et la concentration de sclérostine sont augmentés. De manière intéressante, et cela reste un champ d’investigation, on ne retrouve pas de concentration augmentée de sclérostine chez l’enfant avec une MRC. En MRC terminale, la concentration de sclérostine semble influencée (concentration plus basse) chez les patients ayant encore une fonction rénale résiduelle. Le premières données en MRC terminale suggèrent un rôle de la sclérostine dans le diagnostique de l’os adynamique (associé à une concentration haute), mais les données sont contradictoires. La sclérostine permettrait aussi de prédire la perte de masse osseuse (mesurée par DEXA). Il y a également des données contradictoires sur le rôle de la sclérostine sur la survie du patient avec MRC.
Il existe encore bien des inconnues sur cette protéine et bien des limitations, notamment dans le dosage de la sclérostine plasmatique qui pose question. Néanmoins, nous entendrons de plus en plus parlé de cette protéine et la raison en est très simple et néanmoins importante : il existe en effet un traitement à base d’anticorps anti-sclérostine, traitement qui a déjà été testé et s’est révélé efficace chez la femme ostéoporotique.
Raised sclerostin levels in CKD
Good correlation between bone and plasma sclerostin levels.
PTH stimulates scelrostin
Scelrostin inhibits osteobalstic activity, favoring bone resorption
High plasma sclerostin levels correlate with decreased BMD.
Targetting sclerostin in CKD MBD: WATCH THAT SPACE...
Anti-sclerostin antibodies already tested for treatment of osteoporosis
Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study.
To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death.
Population based nested case-control study.
Ontario, Canada, from 1 April 1994 to 1 January 2012.
Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes.
MAIN OUTCOME MEASURE:
Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index.
Of 39 879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin.
In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.
ACE inhibitors and Angiotensin receptor blockers (ARBs) have been promoted, to and amongst nephrologists, as the best thing since sliced bread...for the last 30 years, since Barry Brenner and his colleagues came up in Boston (1981-1982) with the Hyperfiltration-Hyperperfusion Hypothesis of progressive CKD: http://www.ncbi.nlm.nih.gov/pubmed/7246778
Since, we , as nephrologists, have been dishing out RAAS (renin angiotensin aldosterone inhibitors) to our patients as smarties...regardless of the growing evidence that they are merely good anti-hypertensives with no added benefits: http://www.ncbi.nlm.nih.gov/pubmed/24092942
This is also in spite of ignored evidence that RAAS inhibitions may accelerate/increase the risk of ESRD:http://www.ncbi.nlm.nih.gov/pubmed/16518351
Now we are told that these agents, are potentially DANGEROUS and associated with:
1. Increaesd risk of AKI: http://www.ncbi.nlm.nih.gov/pubmed/24223154
2. Increased risk of sudden death in older patients on certain antibiotics: Co-trimoxazole and quinolones (above abstract).
3. Increaased risk of CVD complications compared to beta-blockers on HD:
4. Increased risk of Cancer amongst smokers renal allograft recipients:
So from a wonder drug...based on limited and flawed evidence (not once was GFR measured in studies claiming that RAAS inhibitors slow CKD decline...???), to a potentially dangerous class of antihypertensives that accelerate renal functional decline in susceptible individuals, induce AKI in th elderly, may cause CVD complications in HD, associate with sudden death in older people on antibiotics, to respiratory cancer in allograft recpients....took 25 years...!!!!
25 years of flawed clinical trials in CKD and DN...
25 years of misinterpretation of published data...
25 years of ignoring the evidence...
25 years of good Pharma marketing...
25 years of Nephrologists gullibility...
25 years before we ask the question:
HAVE WE BEEN SOLD A PUP....????
Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).
Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.
SETTING & PARTICIPANTS:
3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m2 enrolled from June 2003 through August 2008.
Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration.
Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.
Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories).
There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths.
Urine NGAL was measured only once.
Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.
Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.
What seems to be overlooked by one track Nephrologists and CKD aficonados is that HNAG/Lipocalin has many sources other than the renal tubules including neutrophils known to be a risch source of NGAL and involved in atherosclerosis.
In fact, leukocytosis and a high neutrophil count is alo a risk factor for CVD along with a number of neutrophils release products:
This is also the case for monocytes/monocytosis like releasers of NGAL:
So NEPHROLOGISTS need to take their blinkers off and realise that NGAL, like previous factors before, thought to be relased from a single cell or organ, are pleomorphic factors almost universally released by numerous cells within the body...
Remember Vitamin D and its 1alpha hydroxylation..thought for generations to be unique to the kidney and noiw found to take place in numerous extra-renal cells...
Sio regardless of the kidney, its injury or otherwise, inflammatory markers including Leukocytosis, ESR, CRP, hiyerfibrogenemia, etc...and raised NGLA...are all predictors of CVD and CAD.
BMJ 2014;349:g5448 doi: 10.1136/bmj.g5448 (Published 4 September 2014)
How guidelines can fail us
Fiona Godlee editor in chief, The BMJ
Should patients be offered β blockers if they have ischaemic
heart disease and are about to undergo high risk surgery?
Guidelines from the European Society of Cardiology say that
they should, citing evidence that it prevents perioperative
myocardial infarction. Others are unconvinced and say that the
recommendation should be revoked. Initially set at class 1, the
strongest level, the recommendation was retained in 2011 even
though key randomised trials were discredited. In the most
recent update of the guidance, published last month, the
recommendation still stands, albeit at class IIb.
How does this stack up against the remaining trial evidence? A
meta-analysis published in 2013, which excluded the discredited
trials, found that perioperative β blockade in patients at risk was
harmful, associated with a statistically and clinically significant
increase in mortality. And the authors of that meta-analysis,
writing this week in The BMJ (2014;349:g5210, doi:10.1136/
bmj.g5210), tell a strange and unsettling story of subsequent
events, one that is hard to reconcile with the treasured belief
that medicine servesthe best interests of patients and the public.
Those of us who thought we had seen an end to guidelines drawn
up among vested interests behind closed doors will be
disappointed. In Graham Cole and Darrel Francis’s account, we
hear of a secrecy agreementsigned by the guideline authorsthat
is so secret that even its existence must be kept secret. Where
is the openness on which science depends? We hear of
guidelines being led by the authors of the major trials—in this
case the very trialsthat turned out to have corrupted the evidence
base. Where is the scope for critique of researchers who are in
positions of power? We hear of what I would consider to be too
close a relationship between the society and its journal. Where
is the space for dissenting voices?
I will be interested to know whether readers share the authors’
clear disquiet about distorted priorities. When the series of
randomised trials was discredited and the senior author, Don
Poldermans, dismissed from his post, the European Society of
Cardiology’s statement concluded, “We are saddened by Prof
Poldermans’ situation.” Cole and Francis in contrast saw more
to be sad about in the patients who may have died as a result of
guidelinesthat were based on falsified and fictitious data. Using
the discredited research group’s own formula, they calculated
that the number of iatrogenic deaths might have reached 800
000, with half of those occurring after the research had been
discredited. This estimate, with caveats and cautions, was
published in the society’s journal, the European Heart Journal,
but the article was almost immediately removed. A substantially
revised version, without the estimate of deaths, is apparently
due for publication, but the original article is published as an
appendix to the article in The BMJ this week.
Let me quote from it: “Professional failure in clinical research
is not uncommon. If readers are not watching carefully, journals
are not listening seriously, and guideline writers are not free to
act swiftly, future failures may again risk enduring harm with
global reach. The aviation profession hasled the way in systems
to prevent, recognize,study, and learn from professional failures.
Clinical medicine is now following the same path. We must
develop similar systems for research.”
Cite this as: BMJ 2014;349:g5448
Another sobering account of Publications, Meta-analyses, Key opinion Leaders, Guidelines, Guideline panels, and Big Pharma...
Discerning doctors, Nephrologists and readers of publications and Guidelines have to take more responsibility by critically appraise what is dished out for them...to ultimately protect themselves from malpractice...and their patients from the consquences...Claiming ignorance and blind faith in the published word...can kill!
Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients.
The predictive value of anti-M-type phospholipase A2 receptor (PLA2R1) autoantibodies for membranous nephropathy (MN) recurrence after renal transplantation remains controversial.
Our aim was to monitor anti-PLA2R1 IgG4 activity using a sensitive enzyme-linked immunosorbent assay in 15 kidney transplant recipients with MN, and to test the correlation between antibody titres and MN recurrence.
Five patients never exhibited anti-PLA2R1 antibodies, and one of them relapsed. Ten patients (67%) had IgG4 anti-PLA2R1 antibodies at the time of transplantation and during follow-up. The presence of IgG4 anti-PLA2R1 antibodies at the time of kidney transplantation does not imply MN recurrence (P = 0.600, n = 15). However, a positive IgG4 anti-PLA2R1 activity during follow-up (>Month 6) was a significant risk factor for MN relapse (P = 0.0048, n = 10). Indeed, four patients had persistent IgG4 anti-PLA2R1 activity after transplantation and relapsed. Among them, one was successfully treated with rituximab. Another had persistently high IgG4 anti-PLA2R1 activity and exhibited a histological relapse but no proteinuria while on treatment with renin-angiotensin system inhibitors. In contrast, the six other patients who did not relapse exhibited a decrease of their IgG4 anti-PLA2R1 activity following transplant immunosuppression, including two with proteinuria due to biopsy-proven differential diagnoses. A weak transplant immunosuppressive regimen was also a risk factor of MN recurrence (P = 0.0048, n = 10). Indeed, the six patients who received both an induction therapy and a combined treatment with calcineurin inhibitors/mycophenolate exhibited a decrease of IgG4 anti-PLA2R1 activity and did not relapse, while the four patients who did not receive this strong immunosuppressive treatment association had persistently high IgG4 anti-PLA2R1 activity and relapsed.
The monitoring of IgG4 anti-PLA2R1 titres during follow-up helps to predict MN recurrence, and a strong immunosuppressive treatment of anti-PLA2R1 positive patients may prevent recurrence.
This very interesting observation adds to the evolving knowledge related to IMN and the pathogenic role of anti-PLA2R1 autoantibody.
It encourages the practice of screening potential transplant recipient with a history of IMN for anti-PLA2R1, as the titres of this autoantibody prior to transplantation may guide the immunosuppressive regimen used not only to induce successful induction of tolerability of the allograft but also to suppress anti-PLA2R1 titre, thus preventing, or at least decreasing the risk, of IMN recurrence in the allograft.
A similar approach has been advocated for approaching renal transplantation in aptients with FSGS at higher risk of recurrence in the allograft where screening for, and possibly monitoring, suPAR (soluble urokinase-type plasminogen activator receptor) levels may guide management.
Finally, it would be interesting to know if allograft ischemia and DGF, or even ACR, were associated with a higher incidence of IMN recurrence as damage to the allograft podocytes may expose the antigenic epitopes that trigger the re-emergence of anti-PLA2R1 and the subsequent IMN.
As to the management of the patients who have recurrent IMN with high circulating titres of anti-PLA2R1, a previous report suggested a good response to Rituximab (anti-CD20) therapy, with decreased proteinuria, stabilisation of allograft function and disappearance of the autoantibody.
SHARP Study GRoup.
The SHARP study group showed in their original publication that lipids lowering with a combination of simvastatin and ezetimibe had little effect on overall or cardiovascular mortality in CKD.
They also showed that lipid lowering had no effect on CKD progression.
Now, it seems as if the SHARP study group has embraked on republisihng these findings individually.
In this month JASN (August 2014), a paper entitled:
Effects of lowering LDL cholesterol on progression of kidney disease...NO EFFECT.
But this is a duplicated result to that published in the original SHARP report!?
I am suprised that top quality journals dont preclude publication duplications.
I expect to see over th enext few months more SHARP Publications:
Lipids lowering on CAD: NIL....
Lipids lowering on Overall Strokes incidence: NIL....
Lipids lowering on Non-Cardiovascular Mortality....NIL
Lipids Lowering on Cardiovascular Mortality...NIL
MANY PAPERS IN PROSPCET FOR THE SHARP COLLABORATIVE GROUP...
VERY LITTLE NEW INFORMATION IN STORE FOR THE NEPHROLOGISTS...!
It strikes that Nephrologists are so keen to publish theat they often publish short term, incomplete, underpowered and inaccurate informations...that shape our practice.
Two recent examples, in ANCA associated systemic vasculitis (AASV):
We wre told, by teh authors of the MEPEX trial, that plasma exchange improves outcomes in AASV that is associated with advanced renal insufficiency or dialysis dependent at presentation; this was based on a 12months, underpowered study with numerous shortcomings and flaws.
THIS BECAME STANDARD PRACTICE WORLDWIDE...
Now we are told, by the same authors, in a larger study with a longer follow-up:
"...Thus, although short-term results with PLEX are encouraging, the long-term benefits remain unclear. Further research is required to determine the role of PLEX in AAV...."
IN OTHER WORDS, NO EVIDENCE THAT PLASMA EXCHANGE MAKES ANY DIFFERENCE ON PATIENTS SURVIVAL OR EVEN DIALYSIS DEPENDENCY...
Another example, from the same group of experts (EUVAS), has taught us many moons ago that in AASV maintenance therapy with Azathioprine was a good and less side effecst that cyclophopsphamide and we should switch ar 3 months after remission has been induced: CYCAZAREM study.
THIS BECAME STANDARD PRACTICE WORLDWIDE...
Now teh same authors are telling us that perhaps after all that is not the case and switching to azathioprine at 3 months may not be recommended...:
" ...It remains uncertain whether converting to azathioprine after 3-6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy...."
IN OTHER WORDS, THEY DONT KNOW....
These examples, and previous ones, I remember all too well the recommendations of Aspirin + Dipyridamole for mesangiocapillary glomerulonephritis and improved survival over 12 months...only to be proved ineffective over 3 years (Donadio et al in the 80s)...., highlight a number of trends:
1. Over eagerness to publish before being sure of the facts...
2 Publication is more important to some that patients' care...
3. Better publish a poorly documented and incomplete piece of research than wait for the more comprehensive and thorough evaluation of a given intervention...
ULTIMATELY, IT IS US JOBBING NEPHROLOGISTS WHO ARE MISLED...BUT MORE SERIOUSLY, IT IS OUR PATIENTS THAT PAY THE COST OF HASTE...AND SHORT TERMISM....
Two articles have been published this month in the NEJM relating to the PURE study outcomes:
N Engl J Med. 2014 Aug 14;371(7):601-11. doi: 10.1056/NEJMoa1311989.
N Engl J Med. 2014 Aug 14;371(7):612-23. doi: 10.1056/NEJMoa1311889.
The FIRST PUBLICATION, showed that a high urinary excretion of sodium correlates, in a large population (>100,000) in 18 countries worldwide, with systolic and diastolic blood pressure (BP). The slope of the association was steeper for those with hypertension and in older age (>55 years).
An inverse relationship was noted with high urinary potassium excretion.
SO FAR SO GOOD, SO A HIGH URINARY SODIUM EXCRETION = A HIGH SODIUM INTAKE IS ASSOCIATED IN THOSE AT HIGHER RISK WITH A RISE IN BP. THIS ALL THE WAY AS FAR AS SODIUM EXCRETION TO <3G/DAY.
THE SECOND PUBLICATION, showed that a urinary sodium excretion/intake of <3g and >6g/day is associated with increased CARDIOVASCULAR EVENTS. In this study, low <3g/day and high >6g/day sodium intake was associated with increased CVD events. Those individuals between 3 and 6g/day of sodium intake had the lowest CVD. Thus defining a U shape curve with increased risk at high and low sodium intake levels.
In fact, such J/U shaped curve also goes along a similar curve profile for BP and in that respect does not contradict the first study; low BP like High BP are associated with increased mortality. High BP leads to increased risk of CVD and low may reflect the presence of severe CVD and heart failure, specially in the elderly.
Similarly, high sodium/salt intake is associated with high BP and increased CVD whilst low sodium intake may reflect poor health, poor food intake also reflecting an underlying higher comorbidity.
SO WHERE'S THE CONFUSION?
The confusion emanates from such observations (implying that a low sodium/salt intake may be potentially harmful) and current BP guidelines and recommendations including those for CKD patients that advise to reduce the sodium intake of patients to <2g/day:
Thus leaving us in a confused state:
Is lower sodium intake beneficial?
Is lower sodium intake harmful?
Is lower sodium intake beneficial in some age group; >55 years and/or hypertensive?
Is lower sodium intake harmful/unncessary in some age groups <55years and/or normotensive?
Which brings us back to guidelines and healthcare management in general that has to be tailored and adjusted to the individual under consideration as data derived from cross sectional observational studeis like PURE are at best hypothesis generating and not convincing facts we can build our practice upon.
So perhaps we would only be confused if we surrender our own common sense and judgement and apply guidelines an drecommendations blindly...
ONE SIZE NEVER FITS ALL IN MEDICINE...THIS IS HIGHLIGHTED IN REGARDS TO SODIUM INTAKE AS WELL AS BLOOD PRESSURE LEVELS AND CONTROL.
AGE AND COMORBIDITIES HAVE TO BE TAKEN INTO CONSIDERATION WHEN WE MAKE OUR OWN CLINICAL DECISIONS....MORE SALT IN SOME...LESS SALT IN OTHERS...PURE-LY CONVINCING!
So the SHARP study is also negative as far as the impact of STATINS ON CKD PROGRESSION...as it is on other major outcomes such as hospitalisations and mortality in CKD.
YET...IT IS OVERALL SPAN AS A STUDY THAT SHOWED THAT STATINS REDUCED MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) IN CKD PATIENTS....
THIS IS TOTALLY MISLEADING...AS:
SHARP FAILED TO SHOW ANY IMPACT OF STATINS ON:
1. All cause mortality
2. Vacsular/CVD Mortality
3. Non Vascular mortality
5. CAD and its complications
6. Strokes of unknown causes
AND NOW...as previously suggested CKD AND ITS PROGRESSION.
SO WHY IS SHARP SPUN TO NEPHROLOGISTS AS A POSITIVE STUDY THAT REDUCES CVD?
AND WHY DO NEPHROLOGISTS BELEIVE SUCH SPIN?
1. Clearly many Nephrologists are gullible...
2. Many Nephrologists dont know how to read a publication/report critically...
3. Most Nephrologists know little about statistical analyses...
4. Those with a vested interest in a study positive outcomes, including BIG PHARMA, are smart...and take advantage of our shortcomings and fool us to beleive in what is in their interest...
Based upon the fact that SHARP showed BY THE INAPPROPRIATE USE OF SOFT ENDPOINTS AND COMPOSITE ENDPOINTS:
a. A reduction in THE SOFT ENDPOINT OF vascular revascularisation; a procedure freely and subjectively undertaken in many countries, including the USA, by interventionists with little justification, indications or lasting beneficial outcome. In favour of such assumption is the absence of any IMPACT of statins on harder CAD endpoints such as myocardial infarction or coronary related mortality...!!!???
b. A Reduction in ischemic/non-hemorragic strokes; whilst other strokes were not affected AND more significanlty the hard endpoint of death from ischemic strokes is NOT affeceted...!!!!
Also to bare in mind, STATINS INCREASE THE INCIDENCE OF HEMORRHAGIC STROKES as shown in numerous studies including AURORA but also in the recent analysis of the Framingham Heart Study (FRS) where statins increased the risk of cerebral bleeds...
c. SHARP innapropriately used COMPOSITE ENDPOINTS, mixing meaningful and irrelevant outcomes in order to rely on the meaningless (revascularisation procedures) to give the impression that the meaningful MACE are improved on Statins...WRONG AND MISLEADING and a poor and ill informed use of composite endpoint in clinical trials:
In fact, there is a complete disconnect in SHARP between the chosen soft endpoints coronoray revascularisations and ischemic stroke events and the HARD ENDPOINTS related to these such as hospitalisations or MORTALITY....?!
ALTOGETHER SHARP IS A NEGATIVE STUDY SHOWING NO MEANINGFUL EFFECT OF STATINS ON HOSPITALISATIONS OR ANY TYPE OF MORTALITY IN CKD PATIENTS....IT IS BEING SPUN TO CONVINCE US OTHERWISE...SO BEWARE...AS SUCH SPIN HAS ALREADY FOOLED MANY INCLUDING THE KEY OPINION LEADERS WHO DRAFT NATIONAL AND INTERNATIONAL GUIDELINES...BUT IT SHOULDNT FOOL YOU!