Eight major new studies (below) published this year confirm that old is best, and give the lie to costly marketing-hype trials trying to promote newer anti-hypertensive ( beta-, calcium channel- and angiotensin blockers), anticholesterol (statin), antidiabetic and antithrombotic blockbuster drugs.
So the Veterans, MRC, TOMHS, SHEP, ALLHAT, German Reserpine, Cache County, USA, UK, Indian, Chinese and now Turkish, POISE, Australian and the Eniwa antidiabetes, antihypertension and cardiovascular studies. show that one can achieve unsurpassed prevention and treatment of a range of conditions –
overweight or already diabetic, hypertension, stroke, heart-failure, thrombosis, arrhythmia, lipidemia, diabetes, dementia and all-cause premature death –
using low-dose diuretic – ideally co-amiloretic 7 to 13.5mg/d, (or a buchu-dandelion-calmag-potassium equivalent) plus low-dose reserpine 0.05 to 0.1mg (or the herbal parent rauwolfia extract), plus metformin (or the herbal parent galega with other highly effective insulin sensitizer / appetitie regulators), including fish oil 3 – 4gm/day.
Trials for 30 years have shown that only the plant extract metformin reduces all deaths in type 2 diabetes
– In the 20year UKPDS (Holman ea) only metformin lowered all major diseases and deaths by 36%;
– In a Canadian Medicaid Program (Johnson ea), metformin halved deaths in diabetics over 5 years.
Now Servier’s ten-thousand patient ACCORD trial (in North America) confirms that, in contrast to the parallel but less aggressive ten thousand patient ADVANCE trial in the rest of the world, RELATIVE TO METFORMIN, multiple drugs to lower HBA1c intensively below 6.5% increase deaths by 22% by the 2nd yr, from heart attack, hypoglycemia etc.
The higher death rate in ACCORD was associated, inter alia, with much higher use (than in ADVANCE) of insulin; glitazone; incretins; sulphonylurea; statin – none of which prevented a mean of 3kg weight gain. (There was no such weight gain in ADVANCE).
Since humans first became aware of the dangers of human indolence and overeating, observation has shown an inexorable link between increasing overweight and morbidity and premature mortality.
Drug companies (and their paid armies of researchers and lay / academic lobbyists) will not or cannot accept the obvious, that lipidemia and hyperglycemia are not the prime causes of disease that need to be suppressed, but are simply manifestations of disturbed metabolism due to excess calorie (and often salt) intake, leading to insulin resistance.
So they keep churning out new data promoting new antihypertensives, statins and hypoglycaemic agents – which massive studies like TOMHS, SHEP, ALLHAT, UKPDS, PROactive and now ACCORD and the Australian antihypertensive metanalysis debunk.
“Authorities” (which as in South Africa, UK and the EU, downplay metformin or lowdose reserpine / rauwolfia and lowdose diuretics) are mostly (it seems) paid panderers to Big Pharma’s (the drug industry’s) zeal to sell newer blockbusters at any cost. They thereby deny the overweight public the best anti-lipidemia, weight-limiting and antihypertensive agents available.
For the Disease Industry, only disease pays – cheap effective prevention does not.
References / Abstracts:
- NEJM. 2008:358:2545-2559 Effects of Intensive Glucose Lowering in Type 2 Diabetes – The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD).
- NEJM. 2008. 358:2560-2572 Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes – The ADVANCE Collaborative Group.
- BMJ. 2008 May. 336:1121-3. Effect of different regimens to lower blood pressure on major cardiovascular events in older and younger adults – Turnbull & 73 Collaborators, University Sydney, Australia.
The above study (Turnbull et al, 2008) is a metanalysis of world wide randomised trials with different regimens to lower blood pressure in younger and older adults, to compare the effects on the primary outcome between two age groups (<65 v > or =65 years). In 31 trials, 190 606 participants, they found as usual that reduction of blood pressure produces equal benefits with all the different drug classes in younger (<65 years) and older adults. That is, no modern drugs are better than low-dose diuretic at any age.
- Intern Med. 2008. 47:697-703. Metformin and parameters of physical health – Helvaci MR, Yalcin A ea, Mustafa Kemal University, Turkey.
The above study (Helvaci et al, 2008 ) shows that the prevalence of overweight, obesity & it’s high cost on health is increasing. 85% of 369 patients older than 49 years were overweight or obese.
In this trial, overweight patients with BMI 34+-4kg aged 50 to 70 years, desiring weight loss, were divided according to preference for medication, or just diet. Metformin 2.5g/d was given to the medication group. 67% had white coat syndrome or hypertension (HT), 68.8% had dyslipidemia. 53% had impaired glucose tolerance (IGT) or diabetes mellitus (DM).
Initially 143 cases with excess weight preferred diet, 162 preferred metformin. After 6 months there were 3 – 4 fold differences between diet & metformin (p<0.001) according to prevalences of :
- resolved HBP (20% vs 65%);
- Dyslipidemia (18 v 48%) ;
- Hypertriglyceridemia (20 vs 58%);
- Overweight or obesity ( 7 v 28%);
There was also decreased fasting glucose, below 110 mg/dL (20 v 52%), WEIGHT LOSS 3.2kg v 10.4kg – that is, 11.7% lower on metformin.
CONCLUSION: metformin should be initiated in patients with excess weight long before they reach obesity, that is, if weight cannot be kept below about 25kg BMI.
- Hypertension Research. 2008. 31:455-62. Additional small amounts of diuretics improve blood pressure control at low cost without disadvantages in blood sugar metabolism. Kudoh T, Nagawaga T, Nakagawa I. Wajo-kai Eniwa Hospital, Japan.
We followed 147 hypertensive patients from 2002 to 2006. During this period, mean treated SBP decreased from 142+/-11 to 135+/-9 mmHg (p<0.001), and the frequency of patients with SBP>140 mmHg decreased to 14% (p<0.001). We used more diuretics in 2006 than in 2002 (12% rising to 46% p<0.001). In 2006 we analyzed 510 patients who had been followed for at least 2 years. Potassium supplementation was needed in 28% of diuretic-treated patients and7% of patients without diuretics. We found a correlation between the use of diuretics and good SBP control in the entire patient group as well as in patients with diabetes. In the control of diabetes mellitus, we found no statistical difference between patients treated with diuretics and those not. We found diuretics had no adverse effects with respect to new-onset diabetes mellitus.
- Lancet. 2008 ;371:1839-47. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial). Devereaux PJ, Choi P. ea McMaster University, Canada.
The above study was a randomised controlled trial in 190 hospitals in 23 countries of randomised patients, who either had or were risk of atherosclerotic disease, and were undergoing non-cardiac surgery to receive perioperative beta blockade. Extended-release metoprolol (n=4174) or placebo (n=4177) was started 2-4 hours before surgery and continued for 30 days. All 8351 patients were included in analyses; 99.8% patients completed the 30-day follow-up. There were 33% more deaths on metoprolol [3.1%] than on placebo [2.3%; 1.03-1.74; p=0.0317); and double the strokes on metoprolol group [1.0%] than on placebo [0.5%] 1.26-3.74; p=0.0053).
- J Clin Hypertens (Greenwich). 2008. 10:219-25. Prevention of cardiovascular events by treating hypertension in older adults: an evidence-based approach. Firdaus M, Sivaram CA, Reynolds DW. University of Oklahoma , USA.
Systematic PubMed search shows that lowering BP in hypertensives significantly reduces the risk of coronary artery disease, stroke, and cardiovascular and all-cause mortality, and that a low-dose diuretic should be considered the most appropriate first-step treatment for preventing cardiovascular morbidity and mortality. Therapy with >1 medication is often necessary to reduce BP in these patients. There is unequivocal evidence that cardiovascular events can be prevented in older adults, even those older than 80 years, by treating hypertension.
- Stroke. 2008 ;39:1084-9. Long-term fatal outcomes with stroke or transient ischemic attack: fourteen-year follow-up of the systolic hypertension in the elderly SHEP program. Patel AB, Davis BR. Ea UMDNJ-Robert Wood Johnson Medical School, Brunswick, USA.
Incident stroke was significantly decreased by treatment in the (SHEP) Trial, but the reduction in fatal events was not statistically significant. Patients who sustained a stroke during SHEP had more than double the all-cause mortality, cardiovascular death and stroke death at the 14year mean follow-up. CONCLUSIONS: In SHEP, thiazide-based treatment reduced the risk of cardiovascular death after 14 years of extended follow-up.
- J Cardiopulm Rehabil Prev. 2008. 28;92-8. The role of fish oil in arrhythmia prevention. Anand RG, Alkadri M, Lavie CJ, Milani RV. Ochsner Medical Center, New Orleans, USA.
Abstract: Numerous epidemiological studies, case-control series, and randomized trials have demonstrated the ability of fish oil to reduce major cardiovascular events, particularly sudden cardiac death and all-cause mortality. In summary, any patient with documented coronary heart disease and those with risk factors for sudden cardiac death, such as left ventricular dysfunction, left ventricular hypertrophy, prior myocardial infarction, or high-grade ventricular dysrhythmias, should consider fish oil supplementation. At the present time, we recommend doses of eicosapentanoic acid and docosahexanoic acid in the combined range of 800 to 1000 mg/day for primary and secondary prevention of cardiovascular disease.
- JAMA. 1996. 276:1886-92. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group (SHEP). Curb JD, Pressel SL, Stamler J ea John Burns School of Medicine, Honolulu, Hawaii.
A double-blind placebo-controlled trial, the Systolic Hypertension in the Elderly Program at multiple centers in the United States randomised 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients to low dose 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. The placebo group received placebo and any active antihypertensive drugs prescribed by patient’s private physician for persistently high BP.
RESULTS: The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects, active treatment compared with placebo lowered 5-year major CVD by 34%, Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. Low-dose diuretic-based treatment is effective in preventing major CVD events, cerebral and cardiac, in both diabetic and nondiabetic older patients with ISH.