Today October 4 is the second birthday of my dear granddaughter Anushka, so a very Happy Birthday to Anushka Baba.


India has a huge burden of patients with diabetes, there were about 77 million in 2019. The highest prevalence state wise was 13.6% in Chandigarh, with Tamil Nadu having 10.4% and Punjab 10%. Delhi had a prevalence of 26% and Chennai 22%.


Metformin is unanimously considered the first choice in treating type 2 diabetes, and recent randomised cardiovascular outcome trials have shown effectiveness of SGLT2 inhibitors and GLP receptor agonists in improving clinical outcomes. These studies were done in patients with established cardiovascular disease or risk factors.


Treatment of low risk diabetes patients however remains unclear. The GRADE trial attempts to fill the gaps. The trail included more than 4000 patients already on metformin, who had onset of diabetes in the last 10 years. Four classes of drugs were added to metformin. Insulin glargine (long acting), a sulfonylurea namely glimepiride, a GLPR agonist , or a DPP4 inhibitor namely sitagliptin. At base line glycated haemoglobin ranged from 6.8 to 8.5%. The aim in treatment of diabetes is achieving a glycated haemoglobin below 7%.


At an average follow up of 5 years adding insulin glargine to a GLP R agonist was more effective in reducing glycated haemoglobin. Sitagliptin was the least effective in reducing glycated haemoglobin. Hypoglycemia was most at 2.2% with glimepiride. Microvasular complications ( retinopathy, nephropathy, neuropathy ) were similar, but liraglutide reduced cardiovascular outcomes by 29%.


A limitation is that an SGLT2 inhibitor was not included because this class of drug was not approved by the FDA when the GRADE trial began.


The take home message is that in a low risk patient with diabetes begin treatment with metformin, and then add an SGLT2 inhibitor or a GLPR agonist or if need be a long acting insulin.


Importantly a sulfonylurea like glimepiride would also be effective in controlling glycated haemoglobin level. 


All these drugs are available in India at a very reasonable price.


But diabetes is a progressive disease as the GRADE trial has shown with almost 70% pf patients having a glycated haemoglobin above 7% at 5 years.




It is more or less clear that an SGLT2 inhibitor will significantly reduce hospitalisation or cardiovascular mortality in patients both with reduced or preserved ejection fraction. We have the Emperor Reduced, Emperor Preserved, Data HF, and Deliver Trials to confirm this. We also know that there are lakhs of patients with heart failure, with half of them having  preserved ejection fraction. The Deliver Trial reported efficacy of dapapgliflozin in ejection reactions more or less than 60%, the DAPA heart failure trial had shown efficacy in an ejection fraction less than 40%. But there is one important point very few patients were on ARNI class of medicine in the SGLT2 trials, just around 15%. I will come to ARNI very soon.



Sadly heart failure is a progressive disease with 50% patients needing re-hospitalisation in a month and 20% dying in 2 years. This is despite therapy. We have a huge problem on our hands. Over the years multiple randomised trials showed that certain drugs significantly reduce mortality in heart failure patients. Beta blockers reduced death by 30%, a mineralocorticoid receptor blocker by 30%, and an ACE inhibitor by 25%.



Against this background the PARADIGM heart failure trial presented in 2014 was a landmark study that included more than 8400 patients with heart failure and median ejection fraction of only 29%. Around 22% were in NYHA class II, 80% were men, average age was 67 years. Follow up was for 27 months. The study randomised patients to an ARNI or an ACE inhibitor called enalapril. An ARNI is an angiotensin receptor neprilysin inhibitor with sacubitril and valsartan. Sacubitril is the neprilysin blocker and valsartan the AT receptor blocker.



By 27 months the ARNI treated group had a significant 20% reduction in cardiovascular death or hospitalisation for heart failure as compared with the enalapril group. This was a robust difference as these patients were already on a beta blocker, a diuretic, an MRA and 7% had a biventricular pace-maker.



Another trial called PROVE followed 800 patients with an ARNI for one year. There was a significant fall in NTproBNP levels that started falling as early as 2 weeks from treatment onset, and crucially the ejection fraction increased on an average by 9.5% at one year. Such a rise in ejection fraction compares with that of a biventricular pacemaker treatment.



So in conclusion a chronic heart failure patient should be ideally treated with an ARNI, a beta blocker, an MRA and an SGLT2 inhibitor.





Current heart failure guidelines recommend using 4 heart failure drugs simultaneously in patients with chronic heart failure and reduced ejection fraction to get the best results. There could be in fact a 74% reduction in mortality if all 4 drugs are employed; these are a beta blocker, an ACEI or ARNI, an MRA and an SGLT2inhibitor.


The American guidelines mention briefly that in the event of worsening heart failure despite guideline mandated therapy a new drug named vericiguat be used as the Victoria Trial has reported a significant 10% reduction in the primary end point of cardiovascular mortality or heart failure admission in the cohort randomised to vericiguat as compared to placebo.


The Victoria Trial studied 5050 patients of chronic heart failure with educed ejection fraction who worsened in the previous 6 months ( needed hospital admission or injection of a diuretic). The median ejection fraction was 29%, there were 76% males, almost 90% were on 2 guideline medication, while 60% were on triple heart failure drugs. There was modest clinical improvement in a flow up of slightly more than 10 months, with he curve diverging at 3 months.


The dose used was 2.5 mg orally once a day to be titrated to 10 mg once a day.


One tablet of 2.,5 mg vericiguat costs about Rupees 100 in India.


A sub analyses presented in the ACC Meeting this year highlighted that vericiguat was most effective in the cohort of patients with an LV ejection fraction below 24%.


There were more cases of symptomatic hypotension, syncope and anaemia in the vericiguat group but kidney function and electrolytes were unaffected.


I would use the the 4 heart failure medicines mentioned above , before administering vericuguat in a patient with heart failure and reduced ejection fraction (HFrEF).


Also, it cannot be emphasised that despite the American Heart Association recommending vericiguat in worsening heart failure , there was no significant reduction in mortality in the treated group, albeit follow up was less than 11 months.








The largest randomised open label non inferiority trial comparing rivaroxaban with a vitamin K antagonist in more than 4500 patients with rheumatic heart disease associated atrial fibrillation has reported that the composite of clinical events were greater with rivaroxaban than a vitamin K antagonist. This is the INVICTUS trial presented last month in Barcelona (ESC Congress) There was no difference in major bleeding. More than 70% of the patients were women, average age was 50 years, and follow up was for 3.1 years. Mitral stenosis was the valvular lesion in 85% of patients.


There are , however , some gaps still that will need, if possible, another trial.


1) Drop out rate at the end of the trial with rivaroxaban was 22% while it was only 6.5% with a VKA.


2) One cannot extrapolate data to other NOACs such as apixaban or edoxaban.


3) It is probable that the vitamin K antagonist cohort was provided better health care as INR had to be checked once a month. The risk factors may have been managed better.


4) Crucially there is complete silence on the impact of the Covid Pandemic.


5) It would be interesting to learn rate of Covid deaths or vaccine effect on rheumatic heart disease heart, despite lower vaccine uptake in low and middle income group countries.


6) Composite end points were changed at 2 years to include death and myocardial infarction because there was little difference in rate of stroke.



Last month in the European Society of Cardiology meeting in Barcelona the Deliver trial data was presented, which was also published in NEJM. Dapagliflozin, an SGLT2 inhibitor significantly reduced the composite endpoint of heart failure hospitalisation/ emergency visit for heart failure or cardiovascular morality in more than 6200 patients of heart failure with both mildly reduced or preserved ejection fraction. Adverse effects were similar in the treated and control cohorts, in this large randomised study, follow up was for more than 2 years. Dapagliflozin works in diabetic and non diabetic patients. Dapagliflozin had earlier shown significant improvement in clinical outcomes in patients of heart failure with reduced ejection fraction. Crucially, dapagliflozin is easily available in India at a reasonable rate; dose is 10 mg once a day only.




Believe it or not, vaxxed much more likely to get hospitalised or die than the unvaxxed in New Zealand.


Go check the Kiwi Health Ministry official website.


Above applies to boosters as well.


Preprint with Lancet from Denmark reports there is absolutely no difference in deaths with mRNA vaccines.


So why vaccine mandates??


And who is “fully vaccinated ?”




Astonishingly no American journalist, podcaster, or media person ever bothered to interview any Indian physician despite millions of Covid patients getting successfully treated in India.

This reflects conceit or worse a misplaced sense of superiority.

The New England Journal of Medicine has published a “randomised trial” in the latest issue from Brazil that leaves multiple questions un answered.

Worse the discussion section of this paper has not a single line on the limitations of this study.

It should be remembered that the chief editor of The New England Journal of Medicine is on record stating that adverse effects of mass vaccination in children will only be learnt by mass vaccinating them.




The latest issue of the New England Journal of Medicine has published a Brazilian “double blind randomised” trial on ivermectin, which is full of flaws.


We must always keep in mind the chief editor of the journal famously or infamously went on record stating that how would we ever know adverse effects in children if we did not mass vaccinate them against Covid. He said this in an official meeting deciding to confirm vaccinating kids against SARS-CoV-2. 


The Brazilian study is remarkably weak on its take on IVM, riddled with methodical holes that cannot be filled.


Astonishingly the researchers of this study actually began with a single dose of ivermectin but decided to increase this to 3 days albeit still highly inadequate for treating Covid patients.


Unsurprisingly no American doctor , journalist, or podcaster has bothered to interview a single Indian doctor throughout the Pandemic. The reason is quite simple, it is unadulterated conceit tinged with a whiff of racism.


When an uneducated “movie star” slaps a comedian before millions of viewers in the biggest ceremonial show in the world for a mildish joke ,and yet elicits applause from the whose who of Hollywood, you know how steep is the decline in American culture. I will not venture at this point into the corruption that is ubiquitous in good old USA, with penetration into that obscene laptop left behind by the presidents son.


Any way I bring to your kind notice my response to an American “science writer” who is clueless of Covid and it’s treatment, especially the efficacy of ivermectin. This is written against the background of millions of Covid patients successfully treated in India with ivermectin.


Ivermectin fails again 

Don’t hate me for saying it 

Alex Berenson 

Apr 1 

Another strong randomized controlled trial has shown early ivermectin use failed to reduce Covid-19 hospitalizations. 

The New England Journal of Medicine published the results of the trial, which covered 1400 patients in Brazil. The trial was double-blinded and randomized, the gold standard. 

The trial also failed to show that ivermectin had any impact on Covid-19 deaths. 

Dr. Deepak Natarajan <>

12:29 PM (23 minutes ago)



to Alex


Thank God I have not subscribed to your childish gibberish.


I had earlier told you to refrain from commenting on real medicine.


You pass muster with your vaccination stuff relying upon various graphs, which may be a revelation for the lay public.


Medicines are a different ball game.


You need some education apart from merely being a former correspondent for the NYT. A little more discipline and rigour are needed.


Millions of people have been cured in India by ivermectin but your American conceit will not allow you to either examine the data or interact with some Indian doctors (who by the way are as competent if not much more than their American brethren).


The study you quote is full of flaws, and that’s why NEJM has published it.


About 1400 hundred “Covid ” patients were randomised to IVM or placebo.


We are not provided any details as to how these patients were identified. Were they diagnosed by a rapid antigen test or PCR ?


Why was IVM administered on an  empty stomach when every physician worth his salt knows the medicine has to be given with a meal.


Why was the modified intention to treat margin kept only at 24 hours ? 


Why was IVM given only for 3 days ? Why was it given only once a day ?


Astonishingly the researchers provide no clinical characteristics of the patients recruited.


What were the reasons for hospital admission ?


What were the causes of deaths?


How does one confirm IVM was given in 7 days ?


How many given IVM beyond 3 days landed in hospital compared to those getting after 3 days .


Remarkably the editors of NEJM did not bother to publish the limitations of this paper, normally every paper published in this journal is compelled to enumerate limitations of the study concerned.


Maybe in their haste to publish this “double blind randomised” trial the editors decided to forgo this essential component of a scientific paper.


Similarly you in your obscene haste paid little attention to these glaring omissions.


The take home message is that science writers need far greater depth and knowledge to comment on scientific papers, merely questioning a few science chums does not make a credible article, as is done by all science writers with NYT.


Please do consult the big boys before attempting to write on treatment for Covid, losing credibility is quicker than Smith’s slap.


Dr Deepak Natarajan

MBBS, MD, DM (cardiology)

Can a Certain Class of Antihypertensive Pills cause Cancer ?




Two decades ago a large randomised blood pressure trial called ALLHAT reported that a cheap diuretic ( chlorthalidone) was as good, if not superior,to other drugs such as a calcium channel blocker (CCB) or an an angiotensin converting enzyme inhibitor (ACEI). A diuretic was found to be better than a CCB in preventing congestive heart failurE, and superior to lisinopril (ACEI) in lowering BP and in preventing  stroke, heart failure, and angina.



The researchers suggested that thiazide-type diuretics should be considered first line for drug therapy in patients with hypertension, Crucially there were no commercial sponsors involved in this trial.



Hypertension mandates lowering blood pressure to a reasonable extent in order to derive maximum clinical advantage. Substantial reduction in cardiovascular events are observed with optimal blood pressure therapy, with significant reduction in deaths, myocardial infarction, stroke, heart failure and unstable angina requiring intervention. The ALLHAT trial emphasised that there is little to choose between different medicines.



Another class of medicine termed angiotensin receptor blocker (ARB) came into existence soon after publication of the ALLHAT trial . An ARB is used to treat high blood pressure ,congestive heart failure, or diabetes kidney disease.



Over the years ARB’s became popular with most clinicians across the world. Recently, however, regulatory agencies have become concerned about a carcinogenic potential of this class of drugs. ARB’s get contaminated by nitrosamines and azido compounds that are carcinogenic. Randomised trials with ARB’s have shown increased risk of cancers , including lung cancer. 



In 2011 more than 200 million patients were on ARB’s. There must be more now. In 2018 regulatory agencies recognised that nitrosodimetylamine, nitrosodiethylamine, and azido compunds were contaminating ARB’s, and  demanded  recalls of certain lots.



Recently a meta-analysis including 15 randomised trials has suggested a highly significant correlation between cumulative intake of an ARB and risk of all cancers (PLOS; 2nd March 2022). Increased risk was also observed with lung cancer. The meta-analysis included 74,000 patients exposed to high dose of an ARB compared to 62,000 serving as a comparator group. There was a significantly increased risk in all cancers when an ARB was used for more than 3 years, and significant increase in lung cancer when the drug was employed for 2.5 years only.



As opposed to above when an ARB was used at a low dose, and for a shorter duration of time, there was no signal of increased risk in cancer. This meta-analysis was done at a trial level, and therefore effects of age and smoking status could not be examined. Irbesartan, losartan, candesartan and valsartan were found to be associated with raised cancer risk. 



In 2015 however a patient level meta-analysis does by an FDA researcher clearly showed significant increased risk of lung cancer by 24%, and worryingly survival of only 34% of these patients at one year. Predictably, FDA lawyers redacted enough data to prevent publication of this research. Moreover FDA refused to review the data or add a warning in the product package.


Two big trials with telmisartan ( ONTARGET and TRANSCEND) were published in 2008.The TRANSCEND trial stated “a higher rate of malignancies was observed in patients treated with telmisartan than in those treated with placebo” and “so far, there is no evidence that ARBs are associated with a higher risk of malignancies, chance findings due to multiple testing cannot be excluded”. Similarly, in the ONTARGET trial telmisartan was associated with increased risk of can her by 12-14%.


Importantly, ACEinhibitors had no effect on incident cancer in long-term randomized controlled trials including more than 60.000 patients (RR 1.01 [95% CI 0.95 to 1.07]) .


Also, given the numbers needed to harm of 120 for one excess cancer ,and 464 for one excess lung cancer, it can be projected that if 200 million patients are exposed to daily high doses for 4.7 years (or equivalent), approximately 1.7 million excess cancers (and 430,000 lung cancers in 4.6 years) could be potentially caused by this class of drugs. 


Also, there is actual evidence that ARBs may be inferior to many other classes of antihypertensives for prevention of mortality and cardiac morbidity. For example, while ACE inhibitors reduce total mortality and risk of myocardial infarction in hypertensives, ARBs do not reduce the risk. ARBs have not been shown to reduce myocardial infarction, even in placebo controlled trials.


It is imperative that more research is conducted regarding the association of increased cancer risk with ARB’s because of their wide use in patients with heart failure and hypertension. A temporary pause would not be difficult because as mentioned earlier there are multiple drugs that are equally if not more effective. 





1) Risk of cancer with angiotensin-receptor blockers increases with increasing cumulative exposure: Meta-regression analysis of randomized trials. PLOS 2nd March 2021.



2)  Burton TM. Dispute Flares Inside FDA Over Safety of Popular Blood-Pressure Drugs. 2013. https:// (last accessed on Janu- ary 5, 2022). 


3) Center for Drug Evaluation and Research Application Number: 206316Orig1Orig2s000 MEDICAL REVIEW(S). 2015. 206316Orig1Orig2s000MedR.pdf (last accessed on January 5, 2022). 


4)Nissen SE. Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol 2010; 11:605–606. PMID: 20542469 


5) Strauss MH, Hall AS. Angiotensin Receptor Blockers Do Not Reduce Risk of Myocardial Infarction, Car- diovascular Death, or Total Mortality: Further Evidence for the ARB-MI Paradox. Circulation 2017; 135:2088–2090. PMID: 28559493 


6)Singh A, Bangalore S. Do angiotensin receptor blockers prevent myocardial infarctions as well as other initial therapies? Curr Opin Cardiol 2012; 27:381–385. 0b013e328353bc68 PMID: 22525329 


7) Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or calcium channel blocker vs diuretic.The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) JAMA. 2002;288:2981-2997 


8) Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358:1547–1559. NEJMoa0801317 PMID: 18378520 


9)Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008; 372:1174–1183. S0140-6736(08)61242-8 PMID: 18757085 


10) Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008; 359:1225–1237. NEJMoa0804593 PMID: 18753639 











You know you are screwed when “fact checkers’ on Covid vaccination are funded by a foundation with massive stocks in Johnson and Johnson, a company making DNA vector vaccines.

It cannot get worse than this.

In-your-face scams have become the fashion this year.

The results are bound to be disastrous.

No wonder they are licking their lips in anticipation of jabbing 6 months old.

In the current world fiscal power is infinitely more powerful than  nuclear energy.



Acute heart attack or ST-segment elevation myocardial infarction remains the biggest killer on the planet. More people succumb to an acute heart attack in a year than diabetes, hypertension, cancer, or lung disease. Importantly, Covid 19 is certainly not one of the biggest killers.


In the event of a heart attack one artery supplying the heart is completely blocked; that is 100% occluded. There are usually 3 coronary arteries supplying blood supply to the heart. The artery that gets totally blocked is termed the culprit artery. 


The best treatment for an acute heart attack is to get to the closest hospital with a cath lab at the earliest. Time saved is heart muscle saved. The blocked artery needs treatment with coronary angioplasty and stenting to restore blood flow to the dying cells in the after heart.


In some patients another coronary artery may also be blocked, this is the non-culprit artery. It was believed earlier that the union culprit vessel is best left alone during the index procedure. But a large randomized trial, the COMPLETE trial, including more than 4000 patients with acute heart attack showed that opening up both the culprit artery and the non-culprit artery provided significantly better clinical outcomes than treating the culprit vessel alone. The composite of death and myocardial infarction was reduced from 10.5% to 7.8% in a follow-up of 3 years. The COMPLETE Trial was published in the New England Journal of Medicine in September 2019.

The decision to stent the non-culprit vessel was taken if it was blocked 70% or more, and if the blockage ranged between 50% to 69% stenting was done when the fractional flow reserve (FFR) was below 0.80. Usage of FFR in the cath lab confirms whether a 50% to 69% block is actually producing schema in the heart muscle being supplied by the non-culprit vessel.


This year another big randomized trial from France that included more than 1100 acute heart patients documented that using FFR for a non-culprit vessel having a 50% to 69% did not provide a clinical advantage over visual appearance during coronary angiography. The reason may be that in the setting of an acute heart attack FFR may be underestimating the physiological ramifications of a blocked artery.


Hence currently the take-home message should be that stenting of both the culprit vessel and the non-culprit vessel should be done either in the same hospital setting or within one and a half months of the heart attack if the non-culprit artery is 70% or more blocked regardless of ischemia.


 But in case the non-culprit vessel has a block of 50% to 69% the patients should be assessed for ischemia by FFR after a month of the index procedure. In case there is a block in the non-culprit artery of less than 50%, treatment is medical management by pills.


Crucially the patient must get to the closest heart hospital as quickly as possible.



Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial



Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study



Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19 – A double-blind, randomized placebo- controlled trial.



Vaccinating people who have had covid-19: why doesn’t natural
immunity count in the US?
Cite this as: BMJ 2021;374:n2101









Clearly vaccines are not working as promised.


Vaccines do not stop infection, transmission nor serious disease.


In Israel, right now, almost one third of patients hooked to a ventilator are fully vaccinated.


Israel also has the highest number of Covid cases per million despite being one of the highest per capita vaccination rate in the world.


There is a deliberate attempt to erase the reality of successful early treatment by cheap drugs by certain powerful forces with vested interest.


Mass vaccination is definitely not the answer to the current Pandemic.


Especially when cheap, safe and effective drugs are available to tackle the Covid virus.