Tag Archives: coamiloretic

UPDATE: THE FRAUD OF BIG PHARMA MODERN CHRONIC DRUGS

neil.burman@gmail.comUPDATE: see 14 June 2010. The Statin Scam Unravels. 

 

Update: 6 May  2010: this week’s recall of Johnson and Johnson’s Tylenol, Motrin, Zyrtec, and Benadryl due to negligent contamination , in particular of Tylenol for children, leapfrogs America’s household favourite Johnson and Johnson J&J to 2nd place (with at least 6 bad drugs) in the fraudsters mafia roll of dishonour behind the unreachable leaders Pfizer with about a dozen notorious fraud drugs. What is another $81million fine to J&J  that had sales of >$63billion in each of the last two years with profit of above 20%, and that despite the recall still maintained this turnover in quarterly sales for the 1st quarted this year? 

The major thing is that despite J & J’s gross negligence endangering the lives of children, the FDA has taken no other action against them. They terrorize  with armed marshalls  for trivia and shut down small firms making safe health supplements and physicians using them, but the Big Pharma mafia are the darlings of the FDA and Government since they pay such vast amounts in fees and taxes to Govt and lobbyists- politicians and academicians- trialists – that they are untouchable in every country.. 

14 April 2010: So we  can throw away the fraudulent  Pfizer’s fraudulent Neurontin gabapentin  we have been taking? when there never was  evidence that it is as good and safe as it’s parent (our chief brain neurotransmitter aminoacid )  GABA; while it’s younger twin sister  Lyrica – pregabalin– designed  for extension of patent benefits –  is worse  … just like we can throw away the chronic nonsteroidal anti-inflammatories eg Voltaren diclofenac , Vioxx and Celebrex  that are  such heart risks, poor painkillers,   and do  nothing for the underlying destructive chronic disease process. Drugs for massive profit for the beloved Big Pharma Industry that  politicians go to endless lengths to protect.- even Obama and George Brown as witnessed by the multibillion dollar swine flu scam, even now  in 2010 with Obama’s Pharmacare bill. 

 And now Harvard  University shows that even Neurontin and lamotrigine  increase the risk of suicide by42% and 81% respectively. So the long list of fraudulently overmarketed  or hazardous -improperly registered  or prescribed drugs  without adequate trials or obligatory definite  indications-  grows. 

And then there is the Disease Industry hypermarketing technique of Diseasemongering-  promoting previously ignored or unrecognized variable human traits like anxiety, insomnia, lowgrade depression, mild  hypercholesterolemia, female low sexual desire, erectile dysfunction, postural or stress backache- to diseases requiring permanent designer drug therapy eg benzos, viagras, prozacs, statins, NSAIDS nonsteroidal anti0inflammatories;  or “corrective surgery” for all. 

Pfizer,  Bayer, GSK  and  Roche  with the 100% support of their respective government regulators and politicians   continue to vie for top place as the biggest fraudsters of all time – competing with  the food, tobacco, booze, media, vehicle, financial, lawyer, minerals, fuel  and politics  industries..   

Why is this? Because the public – taxpayers and the poorer consumers- are at their most vulnerable, pawns if not cannonfodder and guineapigs  when it comes to trust in government regulators and the giant consumer product  industries – manufacturers and big distributors-  that Govts  regulate – especially the disease and drug industries.  

  And government regulators are controlled by elected politicians   who ( apart from a few altruistic successful honest folk who stand out and are nominated for  or called to office -but not Ralph Nader) –  as  mostly  lawyers or failed businessmen/ workers or carreer trade unionists,   rarely seek higher office  except to further their own financial interests and power lust.   

Winston Churchill and Frank Rooseveldt vie with Margaret Sanger, Mahatma Ghandi  and Nelson Mandela  for honour as the leading persistent (western)  fighter for justice, human rights of the 20th century if not all time, since they were skillful – brave  but above all tough enough (unlike many heroic martyrs) to survive to see it through. 

Hence there is enormous incentive for collusion between politician/ government officials who control the taxes and spending thereof,  and the big businesses that control the big money that escapes the tax officials – including Big Pharma. In South Africa there is no incentive whatsoever for the MCC Medicines Control Council Regulator to work efficiently as all income it generates is absorbed by the Fiscus/Dept Health, which blatantly refuse to produces annual financials for the MCC – effectively a parastatal supposedly under an independent CEO and Board. 

 Below is a list of costly modern disaster or dubious largely chronic drugs and their manufacturers that earn  the profound distrust of consumers: (where there are a proliferation of me-too analogues in a group eg benzos, statins, NSAIDS, bisphosphonates, only the original one or two are listed since they led/lead the pack): 

PFIZER -Wyeth -Searle – Upjohn:  Neurontin; Geodon,  Bextra,  Zyvox,  Lyrica; Lipitor;  Celebrex; PremPro; aspartame; Rezulin;  Viagra; and Ativan=lorazepam/ Xanor=alprazolam – two  of the most addictive   chronic  “anxiolytic” benzos – again, in Wiki and MIMS their  indications are far fewer than the pages of problems they  cause us since the 1970s , papering over and masking symptoms by numbing the mind (as with alcohol and smoking) instead of patients addressing the underlying cause of their anxieties with psychotherapy including learning self-hypnosis control.   

Collectively, Pfizer (the conglomerate of rash clones it has swallowed) has as many modern disaster/fraud  drugs as the next two combined of its  major league fraud competitors: 

Johnson & Johnson – Risperdal  ;   prepulsid;  Tylenol, Motrin, Zyrtec, and Benadryl 

Bayer – Trasyol; Yaz/min Baycol, Paxil, Flonase, Cipro; 

Astra-Zenca – I.C.I. – Seroquel, Nexium ; Crestor,Tenormin, Losec; and thalidomide.. 

Roche  – Xenical, Roaccutane, Tamiflu; Valium. . 

Glaxo-Smith-Kline  GSK -swineflu vaccine; Avandia, Paroxetine. 

Sanofi-Aventis (Hoechst-Rhone-Poulenc)  – Actonel  ; benzbromarone;  swine flu vaccine; Cosaldon -Trental [Cosaldon R was an excellent peripheral vasodilator oxypentifylline plus vitamin E; then Hoechst subtly started downplaying Cosaldon R as it’s patent expired, and introduced the slightly phonetically changed  and far more costly ‘new’   drug Trental pentoxyfylline.. Hoechst would naturally not explain (except obviously on grounds of profiteering from the new patent substitute)  why they substituted an inferior “new”  drug for the better  older version which included the safe dose of vitamin E.] 

 Merck – Vioxx; Zocor,   Fosamax; gardasil. 

Eli  Lilly – Prozac, Zyprexa; memantine ; and DES-diethylstilbestrol, perhaps the most infamous of all commercialized drugs in causing problems even in grandchildren of those so recklessly exposed to it without evidence of benefit. (Eli Lilly was the last company to stop manufacturing it – in 1997! despite evidence of it’s disasterous effects published in 1953, and of cancer from 1971 . ) 

Novartis -Ciba Geigy- Voltaren, swineflu vaccine. 

Abbott labsMeridia=Reductil   

Biogenesis labs – Acomplia; rimonabant  

Bristol-Myers Squibb -Pravastatin;   Plavix, warfarin; And the sustained  cover-up of the COSMIC  metformin  obligatory postmarketing trial  done at the insistence of the FDA on a huge 9000 subjects for 1 year in about 1996/7.   This trial was eventually submitted for publication only in 2004 and thus published in 2005- but for the previous year  BMS and their licensor  the original patent-holder  Merck  denied any knowledge of such a trial although the summary was presented and published a year earlier at a US diabetes congress by the authors, and we supplied the COSMIC abstract- written by BMS researchers who did the COSMIC trial- to BMS and Merck… .        why would BMS and Merck  delay publication of this trial  for so many years, and blatantly deny knowledge of it after the first report of the trial result at a USA diabetes congress ? 

The answer can only be the predicted- because it confirmed in the biggest metformn trial cohort ever- 8000 patient-years- that metformin in diabetics gave zero significant adverse drug effects, with the all-cause deathrate in fact 9% lower than in those on other conventional antidiabetic therapies; and  four major diabetes prevention  trials of metformin in four continents confirmed that it at least halves the incidence of new diabetes- with zero significant adverse effects; and in the intervening years between this trial and it’s result publication, both BMS and Merck developed and launched their respective combinations of metformin and a sulphonylurea (M + SU) . This despite the fact that it was clear since at least the 1970s that the addition of sulphonylurea to  metformin is a desperate last resort since it is fraught with risk of hypoglycemia and reversal of the reduction in fatness produced  by metformin alone.           

A new  retrospective study just published from the UK patient database confirms the  folly known all along  of combination of SU with metformin in that  that over a mean of 4 years on therapy, the metformin+SU therapy reduced all-cause mortality by 23% compared to SU alone; while metformin alone compared to SU alone reduced mortality 1/3 more ie  by 30% – with trivial risk of hypoglycemia. This was similar to the outcome in the 20year UKPDS RCT, where metformin reduced all-cause mortality by 36% over a mean of 13 years, making it the safest and most effective  drug ever patented for  chronic degenerative  disease. . 

And note the cynical folly of the many manufacturers of the grossly overpromoted and overprescribed  bisphosphonates and statins  – which  have numerous serious adverse effects and  should be last-ditch therapy in metastatic bone cancer and in rare  serious hyperlipidemia, not for osteoporosis, not for mild to moderate lipidemia and certainly not over-the-counter as profiteers crave. 

ENDURINGLY BENEFICIAL MODERN CHRONIC DRUGS: 

The above drugs contrast with vey  few modern chronic designer drugs that are still the leaders in their fields, whether as original or generic – although none of them has been shown to address all-cause mortality and pathogenesis. 

Pfizer’s Norvasc=amlodipine  is a rare modern designer exception – dating from the late 1980s,  it’s patent has only just run out-  proving it’s enduring worth for longterm hypertension therapy as the premier 4th-line drug to add when reserpine 0.125mg plus amiloretic 1/2 (ie HCT 25mg + amiloride 2.5mg)  daily are inadequate for optimal control; with very low risk of serious adverse effects. 

BMS’  Captopril & Merck‘s  Renitec – angiotensin converting enzyme inhibitors ACEI –  date from the mid-late ’70s, and while they were and are the first of the invaluable ACEI inhibitors, 5th line antihypertensive drugs for common use, they have formidable potential for lifethreatening adverse effects- but they are on essential drug lists. In the past dozen years big pharma has attempted to substitute angiotensin 11 receptor blockers ARBs, for the aging ACEI,   but a recent metanalysis shows that neither group of drugs significantly lowers fatal or nonfatal cardiovascular events- and they all (unlike reserpine + coamiloretic + amlodipine) have risk of life-threatening  adverse effects. 

DRUGS FROM THE GOLDEN AGE: 

Virtually all other current  designer drugs of enduring and safe worth for chronic longterm use originated from the golden era of innovative and enduring designer drugs mostly around WW2 up to the 1960s: 

The modern  birth control OC pill taken chronically  by millions of women for up to decades for either contraception or symptom control, certainly dates enduringly and endearingly  from the post war Golden Era  as     Estinyl (Schering 1930s)  , with  or alternatively just a  progestin. Modern preparations are relatively so safe that they are the preferred contaceptives for millions of young women.  But we have just seen two young women unwisely started on Bayer-Schering’s Yaz/Yasmin develop in one case hypertension and major weight gain, the other hives- so such innovations are not necessarily better than established brands of OC . 

MSD’s 40year old Sinemet still the firstline gold standard for Parkinsons; Moduretic- amiloretic/ amilozide- still the first drug and permanent baseline  (in low dose eg half tab3 x a week or 1/4 – 1/2 a day) for hypertension; Epilim valproic acid for epilepsy; Tryptanol; 

Sanofi-Aventis Hoecht’s Lasix furosemide still the leading diuretic for  chronic severe heart failure, cirrhosis, nephrosis. 

Merck’s 80yr old metformin- the only laboratory – originated drug (a teak of the galega plant’s biguanide) that reduces all-cause mortality – by no less than 36%, without a single serious adverse effect or mortality if sensibly used; 

Bayer’s Adalat; Aspirin (1899) ; prednisone; 

Novartis-Ciba-GeigyImipramine-Tofranil the first successful commercialise and still enduring major antidepressant. 

Roche’s                            Rivotril; 

Abbott-Knoll                Isoptin; 

GSK’s  Zyloprim;   Imuran;  Panado- still the lead patent mild-moderate painkiller, safe at prescribed dose. 

Pfizer -GDSearle’s  Aldactone; Sulfasalazine; and the 100year old phenytoin -Dilantin, still a longterm lifesaving antiepileptic despite occasional major adverse effects. 

Boot’s  Brufen-  the NSAID nonsteroidal anti-inflammatory drug on Essential Drug Lists,  altho there is no evidence that this group of drugs is essenntial since they do not alter the course of the underlying chronic inflammatory disease or reduce longterm mortality and morbidity, are little if at all better than Panado+- codeine as painkillers, and have formidable risks. http://en.wikipedia.org/wiki/Ibuprofen#History  

Astra-Zenca-ICIs   Inderal was the first of the major new cardiovascular protectant beta-blockers which  are essential drugs., altho all have formidable potential adversity ; as with ACEI, no special optimal favourite has yet emerged;  they have some special chronic indicatiions, including heart conditions and special cases of hypertension. . 

THE BIG PHARMA RAINCHECK  MONEYSPINNERS: 

The US drug industry is reputedly worth >$100billion a year and the biggest industry to >$200billion; and globally some $643 billion, of which the United States produces almost half.  The gross industrial output in USA was apparently about $26 thousand billion in 2008 ie the drug inductry alone approaches 8% of total gross manufacturing output there.   

 It is surely no co-incidence that virtually all  the above  common fraud-drug  pharmacy companies are among the dozen top money-spinners listed on 2009 financials.. But perhaps the biggest racketeering of modern times has yet to be quantified, perhaps  $100 billion  of wasted money on last year’s swine flu  “pandemic” that never happened, in futile mass screening lab tests and vaccines and Tamiflu – giving massive profits  (some companies claimed >$6billion) with total indemnity against litigation to Roche, GSK, Novartis,  Baxter,  Sanofi et al.. The USA-dominated WHO hastily changed the core definition of pandemic early in the North American outbreak so it could declare the nonsensical pandemic to suit the pockets of the profiteering American-European conglomerate and the political lobbyists they employ in Government and beaurocracy… 

 So do we wonder why we can’t trust Big Pharma prescription drugs and doctors’ judgment? Read the stats of a 5years study of the relevant risks,  of  deaths from prescription drugs in USA ( versus natural supplements)  exceeding  over 106 000 to 1.   Thats why Big Pharma and it’s “regulators” like the US Govt FDA, the UK MCC, European medicines Authority EMA, and organized doctors, are so desperate to stop the public buying the supplements people choose- when early and permanent use of balanced natural supplements at least halve serious disease and thus medical consultations, prescription drug use and hospitalization. For profit, only disease (not prevention) pays. 

Of the  103  drugs that achieved  $billion sales  in 2006,: considering the chronic  disease drugs, only valproate and J & J’s contraceptive dates back to the 1980s; Wyeth’s Premarin-Prempro dates back to 1995; and  (omiting duplicate entries) only 33 were oral drugs for chronic major common degenerative (as opposed to infective or malignant or autoimmune )  diseases.  And of the ~33 , only  10 (in descending order of sales value on that list)  even vaguesly justified their  ranking and sales- amlodipine, venlafaxine, bupropion, metoprolol, Viagra ,carvedilol, valproate, ramipril, paroxitine and premarin- 

Reuter’s forecast of the 10  >$5billion raincheques for 2010  include in descending rank for common chronic diseases only the tablets Lipitor, Plavix, Diovan and Crestor- none of which are  proven essential drugs for common average disease use. They are there solely because of heavy marketing by Big Pharma, despite their mediocre results and major potential risks, with far better results given by long-proven natural supplements or by lowdose reserpine-amiloretic combination, then amlodipine . 

Finally, landmark  drugs that were not invented by, or were laregly ignored by,  suppressed by drug companies as medicinals: 

EDTA ethilenediaminetetraacetate was invented 80 years ago but never patented by Big Pharma as a medicine. Yet as an oral nutritional supplement in modest dose it is perfectly safe, and removes toxic lead, mercury, iron and many other heavy metals  (now routinely polluting the environment -food and water- chain)  from the body,  as well as uric acid– being effective preventative against gout, and an antiatheroma agent. It is apparently not a scheduled medicine in either USA, UK or South Africa, being a routine ie harmless – beneficial- food  additive preservative. 

Yet despite the vast evidence favouring fish oil, metformin and EDTA as perfectly safe and effective chronic  anticoagulation, the Disease Industry persists in promoting rat poison- warfarin, dicoumarol– as the common chronic anticoagulant, despite its’ proven risks of promoting hemorrhage, fractures – already known since at least 1998vascular calcinosis already known since 1998 and most recently published last month; and even cancer .   

Metformin is unique, the widest multidisease panacea ever extracted (from a traditional antidiabetic plant)  and patented. Like EDTA it was eventually identified in 1922 by university researchers Werner and Bell in Ireland – but only patented  and produced for routine diabetic use since the 1950s- and deliberately obstructed for use in the USA for another 40 years by the FDA and Big Pharma, which were busy as bees designing and mass marketing far less safe and effective USA sulphonylureas although these were already discredited by the  UGDP  almost 50 years ago, when metformin was ‘rediscovered’ and came into its own. 

Reserpine  also a plant (rauwolfia) extract  remains (with coamiloretic, amilozide)  both in low dose the first-line drug treatment of all classes of hypertension– which since the prevalence of this disease now approachines 50 % in aging adults, makes these drugs amongst the most prevalent essential drugs needed. As even wiki says,  from many major studies over decades, “Reserpine is one of the few antihypertensive medications that have been shown in randomized controlled trials to reduce mortality” – in at least a score conclusive trials of the individual components reserpine, thiazide and amiloride, the triple combination is by far the best firstline therapy, at a cost in South africa of about  $US1 a month.. . But Big Pharma and its profiteer lobbyists continue to suppress the combination fraudulently based on decades-old overdosage data. 

By contrast well over 100 natural micronutrient substances – cinnamon, garlic, ginger, codeine, reserpine, digoxin, huperzine A, galega-metformin and many other plant extracts; vitamins especially B,C,D  in higher dose; , minerals especially calmag,  zinc, chromium, boron, iodine, iron  and even lithium; and human biologicals that deplete with aging like glucochondroitin, CoQ10, acetylcysteine, arginine, cartnitine , GABA, 5HTP  and almost 20  other hormones  replaced chronically – provide almost every chronic major degenerative  disease with the best prevention and treatment, without the almost invariable  risks of  the modern designer chronic drugs discussed above. 

 Since alcohol and tobacco, salt and sugar are still freely sold over the counter OTC  without any restrictions except some  to children , the commonest causes of chronic degenerative disease in more than slightest daily usage, it is obviously lowdose vitamin K,  vitamin C and D, lithium, magnesium, reserpine, metformin- galega  and EDTA that should be mandatorily supplemented in the food chain for the fattening aging 1st-world populations, and allowed OTC purchase;  while indications are severely limited  for prescription of sulphonylureas, statins, bisphosphonates and the dozens of other disaster or dubious  designer drugs listed above.

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Getting to Goal Blood Pressure despite Disaster Capitalism: Why Reserpine Deserves a Second Look

 Lets hear your comments for or against  a return to evidence-based medicine for hypertension, not marketing  hype:

Last week this op-ed column discussed the time-bomb of obesity–  overnutrition, and the wannabe panacea designer drugs of the Disease Industry.

Instead of the narrow Disease-Industry driven multiple designer  prescriptions for hypertension, lipidemia, vascular, depression, dementing and musculoskeletal diseases, the patient – and  lowering the costs of major disease- are far better served by recommending the natural supplements and the old and well-proven few prescription drugs often justified- lowdose amiloretic, lowdose reserpine, metformin., and appropriate parenteral HRT.  

The problem is that Politicians, Treasury, doctor and medicines Regulators, Stock-markets, the Media, Academics and practitioners are all far more impressed by the billion-dollar buying and marketing persuasions of Big Pharma than the truth that is in patients’ (but not the Disease Industry’s) interests.

 

It took 20 years to defeat the FDA-Drug Industry in USA and have old metformin and lithium registered there- so that these are  now worldwide the core drug therapies for type 2 diabetes and bipolar disease respectively  in most  patients.

Until lowdose reserpine plus lowdose co-amiloretic are  similarly restored as the initial therapy of essential hypertension world wide, the growing epidemic of essential hypertension remains in Noam Chomsky’s terms a Failed State of medicine, one of the prime successes of Kissinger-Rumsfeld-Cheyney-Bush- FDA type for-profit subversion of democracy and evidence in therapeutics – and blow the Innocent Casualties


The  August 2007  review summarized below  Getting to Goal Blood Pressure: Why lowdose co-thiazide-reserpine remain the first tier therapy review (which spells out all the acronyms)  from Kaiser Permanente and University clinics in three States,  is  crucial to managing the hypertension epidemic.

 

It amplifies the primacy  of the lowdose reserpine- lowdose co-thiazide diuretic combination over all other drug combinations with new data from the MRFIT study as well as from  the VA, HDFP, SHEP and ALLHAT trials – noting that in low dose these drugs have zero adverse effects (compared to methyldopa, betablockers, ACEI, CCB and ARBs) but a good BP control rate.

 

No antihypertensive drug acts  smoothly and safely for 24hours ie once a day dose except resserpine- which acts for many days; and no antihypertensive drug on its own normalises bloodpressure in the mjority of patients with mild to moderate hypertension.. Thus the ideal primary therapy remains lowdose reserpine plus lowdose coamiloretic.

 

The compelling year-old US review by Barzilay ea  omits a couple of crucial facts/ updates:

 

1. In South Africa, reserpine is still registered,   and recommended by experts as a valuable second-line antihypertensive- but – as in UK and Europe – it has been dropped from the State Clinics’ formulary, for which the responsible authorities ( in  RSA, UK and EU)  blankly refuse to give any scientific reason, since there are none.

This leaves the responsible decision-makers, by default of any other reason, tacitly admitting they bow to the financial enticements  of the pharmaceutical industry who prefer to research and sell more modern ie patented costly blocker drugs and especially patented combinations of the latter- although such combinations have never been proven to be anywhere as good as the lowdose reserpine- lowdose diuretic combination.

 

eg the ASCOT  trial merely confirmed  what was known,  that  brisk diuretic plus a BBlocker is not the best choice for the population tested.    ASCOT was done not in the average new middle-age hypertensive  in a temperate climate,   but like WHI, ALLHAT & SHEP, in  a highrisk older Anglo-Scandian  population mean age  63 yrs living in a much colder climate, many obese (mean BMI 28,3kg), 1/3 smoking, 80% already on therapy, and 60% already with (micro)proteinuria.

   there was no mention of  a good practice control  group ie on effective (eg Ornish- or DPP or UKPDS type) non-drug management, nor a control group on lowdose thazide-reserpine.+- eg amlodipine/ACEI for proper BP control.

Thus there s no basis to say that  a (combination of)  ACEI/ARB/CCB  should be universal firstline therapy.  Even compared to a bad combo like vigorous thiazide + atenolol,  in ASCOT the results of  Secondary endpoint (nonfatal AMI  excl silent AMI, + fatal CHD) barely reached  statistical significance, let alone the failure to achieve the primary endpoint significance (nonfatal AMI + CHD); and allcause mortality did not achieve POEM significance ie  2%pa on ThiazAten vs 1.8%pa on PerinoprilAmlod. (Patient Orientated Evidence that Matters – Shaughnissy & Slater).

      Most major endpoints were predictable, were to be expected in that population:

inappropriate BBlckade caused more PVD, bradycadia, cough, dyspnoea, periph coldness; heartrate was 11bpm higher on the peri/amlo combo, despite serum K level only 0.05mmol higher.  Inappropriate highdose thiazide + BB caused more erectile dysfunction, renal impairmnt & new diabetes-   yet there was no difference in chronic angina, hear failure, lifethreatening arrhythmia.

Perindopril on the other hand predictably caused joint swelling in 14% (vs 3% on thiaz-atenol); and the diuretic-free combo  predictably caused  periph oedema in 23% (vs 6%).  It is salutory that the discontinuaton rate due to adverse reactions was identical 24.7% for the two different regimes – confirming that the new patented combination is no better than even the old thisazide- bblocker one.

2. as hypertension experts  Drs Norman Kaplan, Marvin Moser, Jos Barzilay et al from USA, and South African Hypertension Society’s  Drs YK Seedat, Harry Seftel, Willie Mollentz,  Mark Blockman  et al agree in personal discussion, and by WHO pharmacy expert Kirsten Myhr  2002  and Urquhart 2003,   on what scientific  basis  is lowdose reserpine  restricted, no longer in the first tier combination for primary therapy of essential hypertension? 

It must stay first line both on economy and scientific grounds – although the Drug Industry wishes  it suppressed as has occurred in UK and WHO – EU and RSA State Drug lists, without any scientific reasons given.

Reserpine is not  “a tragic victim of myths, marketing, and fashionable prescribing” as Myhr quotes Fraser 1999 below. The analogy is lithium for bipolar disease, and metformin for diabetes and the prediabetes syndromes (overweight, hypertension,  infertility), which  gold standard old drugs were denied to the USA public  for twenty years  by the malignant control that Big Pharma wielded and still wields through it’s buying power  over the FDA and other Regulators. 

       The progressive suppression of reserpine by the EU and RSA can only be the result of disinformation spread by the New Prescription Designer Drug industry through it’s expert paid lobbyists in Academia, journals  and on Regulatory Committees. 

      Contrary to Fraser, there is no “fashionable prescribing” in socialist -controlled pharmacopoeas like the UK NHS, Europe or the state sector in South Africa- the (supra)national Authorities  have simply bowed to the financial might of manufacturers and banned  reserpine from their formularies, since governments (like the Disease Industry) earn far more from new designer drug registration and  tax revenues than from the old and proven like metformin, lithium and reserpine.

This is the essence  of Naomi Klein’s Disaster Capitalism (The Shock Doctrine 2007),  Al Gore’s The Assault on Reason (2007).

           But  for the same reason that even USA had to licence lithium and metformin – they are the best and proven therapies in their class-  lowdose reserpine must be reinstated as baseline therapy for hypertension in RSA and the EU.

3. Up to now on Medline,

          at least a dozen RCTs show that no single antihypertensive drug does better than lowdose (co-) thiazide. 

          at least a dozen RCTs show that solo lowdose reserpine is at least as good as if not better than any other single drug.

          at least 25 RCTs show that the combination of lowdose reserpine + lowdose co-thiazide/amiloride is unsurpassed

 

– so no drug company has dared to do any more head-on comparative trials .

 

             The latest of these trials – SHEP  and now ALLHAT – after the two definng German Reserpine Group  RCTs (Pittrow ea 1997)  –  show that even as third-line add-on ie in the most resistant cases, reserpine is unsurpassable.   

 

              The reserpine RCTs confirm that lowdose reserpine   corrects some of the metabolic adversity of higher-dose thiazide, without the adverse effects of the newer alpha/beta/ACE/ARB/CCB  blockers.  For safety and efficacy, amlodipine may be the nearest equal of reserpine – but it does not have all the  benefits of reserpine.. New studies confirm that lowdose reserpine is both major antidepressant-anxiolytic,  anti-parkinsonian, and a major anti-addiction herb extract.

 

4. and the Cache County study (2006)    showed that  “the use of potassium-sparing diuretics alone without any other antihypertensive medication was associated with a significant 90% reduction in Alzheimer’s Disease  risk   (aHR, 0.09; 95% CI, 0.01-0.41).

 

 

5. COSTING: Even in mid-2008, in South Africa a vigorous dose of co-amiloretic 13.5mg plus reserpine 0.1mg per day costs RETAIL as little as R15 or US2 a month – and many patients need only half those doses to control mild to moderate HBP. But if bulk bought by the RSA State for the millions of hypertensive state patients, the combination could cost as little as US$0.5 a year for actual ingredients. But in terms of disaster capitalism, such optimal therapy that  greatly improves healthspan and productivity suits  neither the pharmaceutical industry,  nor the State who depend on jobs, fees  and taxes  from a thriving pharmaceutical industry.  When we offered this option two year ago, the experts chose to ignore it…

 

6. IGNORING THE BROAD PATHOGENESIS OF AGING DISEASE: However, all the commercial ie prescription drugs discussed above hardly address the core pathogenesis of common essential HBP. 

The patented drugs deal with salt and water retention and  vasoconstriction, but  none work against obesity- metabolic syndrome, free radiclal lipoxidation inflammation, atheroma, and stress-related  hypercorticolism;  and only ACEI/ ARBs counter-act insulin resistance, tissue glycation ie reduce new diabetes.  

 

eg in the HOPE trial (2000) of ramipril vs placebo in ~66yr  old largely obese vascular-risk patients, the 5year death rate on placebo was 12.2% vs 10.4% on ramipril (-16%, p0.005)-  but if anything there were more noncardiovascular deaths on ramipril (4.3%) than on placebo(4.1%). New cases of diabetes were 1/3 lower on ramipril than on placebo (5.4%).

but  in the Univ Texas metaanalysis of ACEI and ARB trials (2006), these drugs reduced the incidence of new diabetes by only 20%.  

 

But  with marketed antihypertensive drugs, no reduction in the non-vascular scourges of the aging –  fractures, obesity, cancer or dementia –  was reported:

    neither the HYVET-COG trial  (2008) in those over 80yrs, nor the 2006 Cochrane metanalysis showed any benefit in lowering dementia with antihypertensives in hypertensive patients.

     In a 4year study from New Zealand Reid 2007  showed no significant improvement in hip or spine bone density from 50mg HCThiazide a day;    but a 2006 Canadian metanalysis   showed that thiazides  or betablocker or ACEI for hypertension reduced the incidence of any fracture by a significant 14 to 19%.

 

ADDRESSING THE PATHOGENESIS OF PREMATURE AGING DEGENERATIVE DISEASE: The insignificant results of focussing just on antihypertensives- no reduction in obesity, non-stroke dementia, cancer, and small reduction in fractures and dementia-

contrast with the result of 

*appropriate HRT in menopausal women in the WHI and Oulu 10year trials: about onethird reduction in all major events-  fractures, new diabetes, cardiovascular, cancer and dementing problems – and thus in all-cause mortality;

*and metformin in the three major diabetes prevention programs- about 50% reduction in new diabetes;

*and metformin in the UKPDS and Canadian 5 to 20year studies-   reduction of mortality by a third to half;

*and natural supplements for the depleting and polluted  food chain and environment – fish oil plus a simple appropriate blend of the 13 vitamins, +-13 essential minerals, and the ~25 invaluable other antioxidant nitric-oxide booster  biologicals which lower insulin resistance – lipidemia,   hypertension, obesity, free radical  lipoxidation and thus arteriosclerosis; and  all the  other major chronic degenerative diseases of aging: eg CoQ10, arginine, carnitine, ribose, proline,  N-acetylcysteine, malic acid, GABA, 5HTP, taurine, chondroglucosamine,  MSMethane, curcumin, galega, gymnema, coleus, sawpalm etc.

 

ndb

 

E d i t o r i a l  THE JOURNAL OF CLINICAL HYPERTENSION  2007: 9 591-4
Getting to Goal Blood Pressure:   Why Reserpine Deserves a Second Look
Joshua Barzilay,  Kaiser Permanente ea,

 This multiauthor editorial  reviewed several  hypertension trials in which reserpine therapy was used with good results,

and presented  new data from the Multiple Risk Factor Intervention Trial (MRFIT) that also demonstrate  the positive effects of reserpine.They believe that reserpine deserves reconsideration as an effective  antihypertensive medication, especially in combination therapy.


“By 2004, the prevalence of hypertension increased in USA  to 29% mainly as a result of increased  obesity and population age, while blood pressure (BP) control rates improved  to 37%.     Despite this recent success, BP control rates  remain low.  

Reasons for this include  lack of careful follow-up; failure to control systolic BP,  especially in older patients; and therapeutic inertia (ie, failure to increase the dose of medication  or add  another medication when BP is not at goal).

Until recently, even in the best clinical trials,  BP control rates of only 66% to 73% have been achieved even  with a 2-drug combination as initial therapy,

 

“One antihypertensive medication that could be used to improve BP control, especially systolic BP, is reserpine, a centrally acting adrenergic antagonist. It  fell into disfavor years ago, labeled  a relic from the past and an obsolete medication. While its use in westernized countries fell precipitously in the past decades despite its proven efficacy, reserpine is still used extensively  in nonwesternized countries, where health care expenditures are more costconstrained.
In South Africa, for example, it is a second-step hypertension medication after diuretic therapy. In India, low-dose reserpine, in combination with diuretics and hydralazine, is used effectively to prevent renal disease.

Several adverse effects –  depression, gastric bleeding, and breast cancer- attributed to reserpine  in the 1950s and 1960s led to its near demise. . Early in its use, recommended dosages of reserpine  varied from 0.75 mg to 10 mg/d;  but studies using   low dosages  0.05–0.1 mg/d usually in combination  with diuretics) show that reserpine is well tolerated

At current dosing levels, no increase in depression,  dyspepsia or breast cancer have been reported.

 

“The situation of reserpine is analogous in many ways to that of thiazide diuretic therapy. Early in their use, high dosages of diuretics (often up to 200 mg/d) were prescribed, and  associated with  high rates of adverse biochemical effects and little additional antihypertensive efficacy..

“Today, low-dose thiazide diuretics (ie, 12.5–50 mg/d) are the recommended first-step agents in the treatment of hypertension.

Early hypertension outcome studies, such as the Veterans Administration (VA) Cooperative Studies in the 1960s, the Hypertension Detection and Follow-Up Program (HDFP) in the 1970s, and MRFIT in the 1980s, established that low-dose reserpine therapy was an effective treatment for most hypertensives.

 

Table. Change in BP With the Addition of Step 2 Medication in MRFITa
                                                        SBP                                 DBP
STEP 2 MEDICATION     N         MEAN         SE                     MEAN              SE
Reserpine                         445        –7.8            0.6                     –6.5                 0.4
Methyldopa or propanolol 370      –4.1            1.1                     –3.8                 0.7

 

“Further analysis of the MRFIT dataset, presented here for the first time (Table), indicates that  reserpine add-on therapy in men treated with diuretic monotherapy through the first year of the  study was more successful in lowering systolic and diastolic BP than  propranolol or methyldopa..


“Several VA cooperative studies in the 1980s also demonstrated the efficacy of reserpine: In the Hypertension in the Elderly VA study, men aged 60 years or older, approximately 40% did not respond to thiazide monotherapy, and second-step medications were added. Results showed equal efficacy of methyldopa,
hydralazine, metoprolol, and reserpine and equal duration of action. Measures of cognitive behavioral effects, such as depression, diminished cognitive abilities, and changes in activities of daily living, did not differ between the groups; however, reported adverse effects and withdrawal due to drug intolerance were higher with methyldopa.

 

“With reserpine there were no reported adverse effects that were increased, but with reserpine  postural dizziness and headache were reduced, and serum cholesterol levels decreased  the most  (–16 mg/dL).

 

“The most recent clinical hypertension trial  reporting on the use of reserpine was the Systolic Hypertension in the Elderly Program (SHEP)  in more than 4700 adults aged 60+ years;  it  was the first to demonstrate the efficacy of low-dose antihypertensive medication in preventing stroke (by 35%) and cardiovascular events (by 32%) in people with isolated systolic hypertension (defined as systolic BP >160 mm Hg and diastolic BP <90 mm Hg). The active treatment group (n=2365) received a low dosage of chlorthalidone (12.5–25.0 mg/d) with a step up to atenolol (25.0–50.0 mg/d) or reserpine (0.05–0.10 mg/d), if needed. During the 4.5 years of average follow-up,  8% (n=193) received  reserpine over a mean exposure period of 1.7 years .For reserpine, the relative risk (vs nonuse of reserpine) and 95% confidence intervals were 0.65 (0.26–1.59) for mortality, 0.27 (0.04–2.26) for stroke, 0.93(0.29–2.96) for coronary heart disease events, and 0.55 (0.20–1.49) for cardiovascular disease events. 

All these  values are considerably lower than those associated with atenolol use (0.84;  1.34 ;1.04 and 1.07, respectively),  a medication still in wide use. These  results are similar to those of MRFIT.

Given the new results  from MRFIT and the results of the VA Cooperative trial and SHEP, it would appear that reserpine still has a role in the management of hypertension. The question arises: how should it be used?

 

“It is now commonly accepted practice to initiate antihypertensive therapy with 2
antihypertensive medications in persons with stage 2 hypertension.


“The most common combination  is a diuretic with either an angiotensin converting  enzyme (ACE)  inhibitor/angiotensin II receptor blocker (ARB) or a calcium channel blocker  (CCB).

 In many cases, especially in older persons and those with diabetes and obesity,

2 medications are not completely effective and ≥3 medications  may be required, as experienced in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial  (ALLHAT).  

 Persons with diabetes usually are obese. When obesity is centrally distributed, insulin resistance is present, and with it the metabolic syndrome. It has been estimated that among US adults aged 60 years or older, ≈65% have hypertension and ≈40% have the metabolic syndrome.

 One consequence of insulin resistance is increased sympathetic tone and thus elevated BP.

In these obese individuals,  blockade of increased sympathetic tone  with reserpine, through reduction of  peripheral and central noradrenaline stores, may have a salutary effect in BP control.

 

“Combining a diuretic, which decreases the excess fluid volume associated with the metabolic  syndrome,  and an ACE inhibitor/ARB or CCB,  which protects endothelial function and/or decreases vascular resistance,  represents an effective  treatment plan for the clinician in BP management.

This is in keeping with  growing awareness that combination therapy is an effective means of treatment  but more may have to be done in some patients. The use of reserpine, an additional option, may provide for improvement in management in these individuals. Reserpine is an effective BP-lowering agent. It
is most effective in the elderly and the obese, often when systolic BP is the limiting goal BP measure. It has a very long duration of action (days) and may therefore be helpful in partially adherent patients.

 

“At present, there are no pharmaceutical advocates for the use of reserpine or a clinical trial to test its effects on clinical outcomes. It will only be at the behest of the medical community that consideration be given for the use of low-dosage reserpine (0.05–0.10 mg once daily, often at bedtime) to better control BP. While the exact place for its use can be debated, we believe it deserves strong consideration.”

 

MEMORANDUM  From: Kirsten Myhr, MscPharm, MPH, Member Expert Advisory Panel on Drug Policies and Management http://archives.who.int/eml/expcom/expcom12/kmyhrmemo.docDate: 6 April 2002  To: Co-ordinator, WHO EDL Committee meeting April 2002

Subject: Revision of the essential drugs list

Reserpine

“I think there is documentation to support keeping it as a low cost alternative. Here are five relevant references from Medline, note in particular that it is included in the guidelines in South Africa, even after a recent revision of the guidelines.

1. Kronig B, Pittrow DB, Welzel D, Weidinger G. Different concepts in first-line treatment of essential hypertension. Comparison of  low-dose reserpine-thiazide combination with nitrendipine monotherapy. German Reserpine in Hypertension Study Group. Hypertension. 1997;29: 651-8.     

 2. Griebenow R, Pittrow DB, Weidinger G, Mueller E, Mutschler E, Welzel D.Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Blood Press. 1997; 6(5): 299-306.

3. Manyemba J. A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension. Cent Afr J Med. 1997 Dec;43(12): 344-9.

4. Seedat YK. Hypertension in developing nations in sub-Saharan Africa. J Hum Hypertens. 2000 Oct-Nov;14(10-11): 739-47. Review.

5. Hypertension clinical guideline 2000. S Afr Med J. 2001 Feb; 91(2 Pt 2):163-72.

6. Fraser HS. Reserpine: a tragic victim of myths, marketing, and fashionable prescribing.
Clin Pharmacol Ther. 1996 Oct; 60(4): 368-73.