1.  

    JACC HEART FAILURE MAY 10;2018

     

    Cardiac resynchronisation therapy (CRT) or biventricular pacing has rapidly evolved as the bedrock for treating patients with severe hear failure on optimal medication (beta blockers, aldosterone antagonists, and ACE inhibitors). It has been observed that CRT improves ejection fraction, quality of life, symptomatic status and above all it significantly reduces mortality. It is most effective in patients of systolic heart failure in NYHA functional class III – ambulatory IV, having LV ejection fraction less than 35%, and QRS duration greater than 120 ms . Crucially the patient should be able to live at least one year. The mechanisms by which CRT improves cardiac function are complex but the paramount reason is it’s ability to synchronise contraction of the failing left ventricle. Left bundle branch block leads to dyssynchrony in left ventricle contraction, which means that all segments of the chamber do not contract uniformly. There is also dyssynchrony in contraction between the right and left ventricles. With establishment of chaotic contraction there is compromise in stroke volume and also cardiac output. CRT also improves b-adrenergic responsiveness and other cellular functions.

     

     

    The MADIT CRT randomised 1820 patients to CRT and no CRT therapy against the background of optimal medical therapy. Continued follow up for 7 years shown that in patients with left bundle branch block there was 41% reduction in death, an absolute reduction of 11% as compared to patients not on CRT. The substantial reduction in mortality was seen in patients already on beta blockers and ACE inhibitors ( and angiotensin receptor blockers). The MADIT -CRT trial included patients in NYHA class I and II.

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    More than 10 years ago the COURAGE trial (N Engl J Med 2007;356: 1503-16) had randomised more than 2,200 patients of stable angina to percutaneous coronary intervention (PCI) plus optimal medical therapy or optimal medical therapy alone. Medical therapy consisted of statins, beta blocker, long acting calcium blocker or long acting nitrate. All patients needed to have a 70% stenosis of at least one epicardial coronary artery accompanied with objective of evidence myocardial ischemia. Surprisingly at the end of almost 5 years there was no difference in death or myocardial infarction. In patients with stable angina there was no advantage of PCI and optimal medical therapy over medical therapy.

     

    A few months ago the ORBITA trial (Lancet 2018;391:31-40) reported that there was no significant increase in exercise time when PCI was compared to a sham PCI procedure in stable angina patients with a single artery that was blocked significantly. The difference was only an insignificant 16.6 seconds at 6 weeks follow up. There were loud cries of changing guidelines in the treatment of stable angina following the presentation of ORBITA data. Medical therapy when prescribed optimally was as good as an invasive procedure in patients with stable angina. The study included only 220 patients and had a brief follow up of only 6 weeks.

     

    LANCET 2018; 391: 31-40

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    Heart failure (HF) is an awful disease, there are lakhs of patients in this country who barley get treated. A considerable proportion of HF patients have systolic dysfunction or reduced ejection fraction of there left ventricle. Thus is also known as heart failure with reduced ejection fraction or HFrEF. The burden of severe heart failure continues to escalate . Just about every practicing physician regularly comes across a heart failure patient needing careful treatment and probable admission in hospital. Once hospitalised almost 30% to 40% patients need re-hospitalisation within 6 months. Almost patients are dead due to worsening heart failure or sudden arrhythmia. The majority of current physicians will just not be able to appreciate that as recently as the mid ninety eighties there was no effective treatment for heart failure apart from diuretics and digoxin. Neither diuretics or digoxin are known to reduce death in HF. Despite reduction in hospitalisation by angiotensin converting enzyme (ACE) inhibitors, spironolactone and digoxin, the incidence of admission for worsening HF remains quite grim.

     

    The 1990’s witnessed substantial progress in reduction of HF hospital admission. Beta blocker treatment in addition to ACE inhibitors and digoxin reduced risk of hospitalisation by 20% to 30%. The early studies on beta blockers assessed efficacy in patients with mild to moderate HF. The effects of beta blockers on morbidity in patients with severe HF were yet to follow. The COPERNICUS ( N Engl J Med 2001;344:1651) trial was one such pioneering trial that established the role of carvedilol in patients with severe HF. COPERNICUS was a prospective double blind placebo controlled trial that studied the effect of carvedilol on mortality and morbidity in severe HF. Severe HF was defined as breathlessness or fatigue at rest or on minimal exertion, and a left ventricle ejection fraction less than 25%. Patients were already on diuretics (>95%), an ACE inhibitor (>95%), digoxin (65%), spironolactone (20%) or amiodarone (15%). The trial was stopped early after a mean duration of follow up of 10.4 months, because of a highly significant benefit on survival with carvedilol. Notably in this short follow up 24% of patients in there placebo group were admitted for worsening HF as compared to 17% in the carvedilol group, indicating the severity of HF in this trial. Moreover there was no incidence of worsening of HF by carvedilol during start of treatment.

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    The AFFIRM trial ( N Engl J Med 2002; 347:1825-33) had randomised more than 4000 patients with atrial fibrillation (AF) to rate control and rhythm control groups. The researchers had concluded that there was no difference in mortality between the 2 groups, in fact adverse events were similar while deaths were actually a bit more in the rhythm control group. A total of 4060 patients were included in the trial with two thirds having hypertension while the remainder had coronary artery disease. There were 356 deaths in the rhythm control group versus 310 deaths in the patients assigned to rate control by 5 years follow up. More patients in the rhythm control group needed to be hospitalised. Anticoagualation was recommended in both groups. Rhythm control was achieved by amiodarone, disopyramide, flecainide, morcizine, procainamide, propafanone, quinidine, sotyalol and a combination of these drugs. Rate was controlled below 100/min by beta blockers, verapamil, diltiazem, digoxin or a combination of these drugs. The average age of patients studied was 70 years.

     

     

    The next randomised trial comparing rate versus rhythm control was published more than a decade later ( N Engl J med 2016;374:1911-21). This studied AF developing post cardiac surgery. Rhythm control was achieved with amiodarone. New onset post operative atrial fibrillation occurred in almost 700 patients of the 2109 patients enrolled in this trial. Total number of hospital stay was the same in both groups. There was no significant difference in rates of death or over all serious side effects. At 60 days more than 94% patients in both groups had a stable without AF for the previous 30 days. The researchers of the trial concluded that a sizeable number of patients develop new onset AF after cardiac surgery, but there was no discernible difference in hospital stay, mortality or other complications. The strategy of rhythm control did not provide any clinical advantage over rate control in patients with post heart surgery AF.

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    I had wanted to write on the treatment of acute coronary syndrome-unstable angina, but I woke up this morning to learn that the world had turned more unstable, than it had ever been since World War II. Donald Trump has scrapped the Iran Nuclear Deal not because he did not consider it worthwhile but probably more because it was the singular foreign policy achievement of his predecessor. Obama was rightly proud of the Iran Deal because it has stopped the Iranian nuclear program . Iran was no longer feverishly making a nuclear bomb, it had cut down its centrifuges from 20,000 to around 500, uranium stockpile had been reduced from 8 tons to just 4%. Crucially verification by international atomic energy agencies were considered “robust”, which means Iranian nuclear establishments were open to inspection whenever necessary. Trump by reneging on American promise will instigate the Iranians to pursue their making the atom bomb program with a vengeance despite any form of sanctions. The Middle East may once plunge into wars, American lives put to danger, and above all put India in a delicate and vulnerable position.India buys considerable amount of oil to fuel its economy from Iran, and that too not in Dollars but Euros. Why would the North Koreans believe the Americans on any deal? Trump has already reneged on the Paris Climate and Trans Pacific Partnership trade deals. Some now say that Americans rarely take deals signed by them seriously. The Brits, French and Germans are scrambling to salvage the fractured deal. Mr. Putin is yet to issue a statement. The world waits with bated breath for the Iranian response. Do the Iranian resume their military nuclear program? Does the position of their moderate president become untenable? Do the hard liners in Iran strengthen their grip over their government?

     

     

    We however ned to concentrate on acute coronary syndrome. Acute coronary syndrome (ACS), apart from ST segment elevation myocardial infarction (STEMI), consists of unstable angina and non ST segment elevation myocardial infarction (NSTEMI). Unstable angina is worsening stable angina that occurs more frequently, on lesser exertion or at rest. Unstable angina is not associated with a rise in troponin levels or other cardiac enzymes but has ECG changes of T wave invasion or ST segment depression. Troponion and cardiac enzyme levels are raised in NSTEMI. Routine coronary angiography followed by PCI if needed has been shown to provide improved clinical outcomes by multiple randomised trials. The optimal timing for intervention in patients with unstable angina or NSTEMI was clarified by the large TIMACS trial. TIMACS randomised 3030patients with ACS to undergo either routine early intervention (less than 24 hours) or delayed coronary angiography more than 36 hours after randomisation.The primary outcome was death, myocardial infarction or stroke at 6 months. The secondary outcome was death, myocardial infarction o refractory schema at 6 months. Primary angiography was performed in 98% of the early intervention group (median time, 14 hours) and 96% in the delayed intervention group (median time ,50 hours) . At 6 months there was no significant difference in the primary endpoint. There was a 28% relative reaction in secondary endpoint of death, MI or refractory schema in the early intervention versus delayed intervention group, which was significant (10% versus 13%, p=0.003). Early intervention improved outcome in patients at highest risk (one third) but not in the intermediate o low risk groups.

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    2017 ESC GUIDELINES FOR STEMI

     

     

     

    It ia an established fact that an ST-segment elevation myocardial infarction (STEMI)is due to rupture of an atherosclerotic place and the resultant platelet rich thrombus that completely blocks the coronary artery. By 2003 based upon 23 randomised trials it had become clear that primary percutaneous coronary intervention (PPCI) resulted in significantly fewer deaths, re-infarction, and stroke, as compared to fibrinolysis or thrombolytic therapy. PPCI is superior because of greater achievement of TIMI 3 antegrade flow than thrombolysis and stabilisation of the ruptured plaque. There are less chances of a re-infarction, greater salvage of myocardium and significantly fewer intracranial bleeding with PPCI as compared to thrombolysis. PPCI therefore has become the treatment of choice for STEMI if done in time and by experienced operators.

     

    Experimental studies indicate that amount of myocardial salvage depends on the speed in which the occluded coronary artery is opened up; the sooner PPCI is done the greater the benefit. Hence the cardiac adage “ time is muscle.” Cardiologists became greatly interested in a combination strategy of thrombolysis followed by PCI or “ facilitated PCI.” Facilitated PCI was also called “pharmaco-invasive PCI” by some. It was theorised that by administering a thrombolytic agent as early as possible after symptom onset there would me more infarct related arteries open to some extent by the time PCI was attempted in the cath lab. However early studies combining thrombolytic therapy with immediate PCI reported increased rates of death, coronary occlusion and hemorrhagic complications. The biggest dampener was the ASSENT-4 PCI trial (Lancet 2006;367:569) that randomised 4000 patients of STEMI less than 6 hours duration to PPCI or to standard PCI soon after full dose tenectaplase. All patients got aspirin and a bolus of unfractionated heparin. The safety monitoring board had to abort the study because of significantly greater stroke during hospital stay, reinfarctiron and repeat target vessel revascularisation within 90 days in the study group. The researchers concluded that full dose tenectaplase with thrombolytic co therapy (preceding PCI by 1-3 hours) cannot be recommended.

     

    LANCET FEBRUARY 18, 2006

     

    In the same issue of the Lancet (2006;367:579-588) a review of randomised trials comparing primary and facilitated PCI for STEMI was published. The authors identified 17 trials of STEMI that included a little more than 4500 patients of STEMI. Despite 2-fold increase in the number of patients with TIMI 3 flow in the facilitated PCI group compared to the PPCI group, there was significantly more mortality, re-infarction and urgent target vessel revasularisation. Facilitated PCI was associated with higher rates of major bleeds. The conclusion drawn was that facilitated PCI offers no benefit over primary PCI in the treatment of STEMI, and should be actually avoided. The meta analysis which included data from the ASSENT-4 PCI trial, showed that increased mortality was restricted to studies that used full dose thrombolytic therapy as part of the facilitated strategy. The FINESSE trial randomly assigned 2453 patients in a 1:1:1 treatment allocation to half dose reteplase with abciximab (GP 2b/3a inhibitor), abciximab alone or to primary PCI. At 60-90 minutes patients assigned to facilitated therapy had more ST segment resolution and more patent arteries with TIMI 3 flow before PCI. These benefits however did not translate to lesser death, heart failure, or cariogenic shock through 90 days. There was increased intracranial haemorrhage and significantly more major bleeds in the facilitated PCI groups.A patent artery does not guarantee myocardial perfusion. In fact even though 90% of patients may have TIMI 3 flow after primary PCI, only 29 % have normal myocardial perfusion. Potential explanations for impaired myocardial perfusion despite an open infarct related coronary artery may be distal embolisation of atherosclerotic debris, capillary edema, myocardial edema compressing microvasculature, and plugging by inflammatory cells.

     

    LANCET FEBRUARY 18, 2006

     

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  7.  

    GENE ALLELE ON CHROMOSOME FROM EACH PARENT

     

    Antiplatelet therapy is the bedrock of percutaneous coronary intervention (PCI). A combination of aspirin combined with a P2Y12 inhibitor is given orally to the patient for a duration of at least 12 months subsequent to deployment of a drug eluting stent (DES). Recently some studies have shown equal efficacy when dual anti platelet therapy (DAPT) is provided for as little as 3 months with second generation DES. In terminational guidelines recommend ticagrelor or prasugrel as class 1, with clopidogrel to be administered if the former are not available or not tolerated. Clopidogrel remains as the anti platelet of choice in India, because of lower cost and ease in procuring the medicine. Clopidogrel, however is a prodrug, which means that a liver enzyme called CYP2C19 is needed to activate it. Clopidogrel is able to prevent platelet aggregation only after it is converted to its active metabolite by CYP2C19.

     

    It is also well known that a considerable fraction of patients have genetic variants of CYP2C19, that render the patient unable to activate clopidogrel to its active form. These patients remain at risk for stent thrombosis, death, myocardial infarction and stroke due to insufficient clopidogrel induced platelet inhibition. A number of alleles (or variants) of CYP2C19 have been identified. The enzymatic activity of CYP2C19 can be decreased, increased, or remain normal depending on the allele carried by the patient.

     

    The 1* allele is the normal copy, which means clopidogrel is effective in the patient. The 2* allele is present in 25% to 50% patients ; this allele makes the patient incapable of activating clopidogrel and therefore they are at increased risk of stent thrombosis. Similarly, the 3* allele , present in 1% to 7% patients, also renders the patient incapable of metabolising clopidogrel, and they too therefore are vulnerable to stent thrombosis.

     

    The 17* variant present in nearly 40% of patients actually increases CYP2C19 activity, there is higher production of active metabolite and better clopidogrel induced platelet inhibition.

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    Recently a 33 year old man who had undergone primary PCI for acute anterior ST segment elevation myocardial infarction (STEMI) with a bare metal stent inserted in the proximal left anterior descending coronary artery a little more than 8 years ago presented with rest angina of increasing severity in the previous 2 days. The twelve lead ECG showed ST segment coving in precordial leads and his troponin was considerably raised. Coronary angiography revealed in stent restenosis (ISR) accompanied by very late stent thrombosis (VLST). The patient was successfully treated with intracoronary tirofiban bolus followed by intravenous infusion of irofiban alongside balloon angioplasty (BA) with successive larger diameter balloons at high pressure. The patient was discharged the next day in stable condition on dual antiplatelets (that included ticagrelor),a statin, and an ace inhibitor.

     

    BARE METAL INSTENT RESTENOSIS WITH VERY LATE STENT THROMBOSIS , 8 YEARS AFTER PRIMARY PCI FOR ACUTE ANTERIOR STEMI (RED ARROW). PROXIMAL LEFT ANTERIOR DESCENDING CORONARY ARTERY

     

    BALLOON ANGIOPLASTY FOR BMS-ISR PLUS INTRACORONARY BOLUS OF TIROFIBAN FOLLOWED BY OVERNIGHT INTRAVENOUS TIROFIBAN INFUSION.

     

    POST BALLOON ANGIOPLASTY FOR BMS-ISR CHECK ANGIOGRAM, TIMI 3 FLOW WITH NO RESIDUAL STENOSIS.

     

    Very late stent thrombosis occurs  in  BMS,  albeit at a lower rate than with DES. In stent neoatherosclerosis with ruptured plaque and thin cap fibroatheromas has been observed in BMS. Atheroscrelotic plaques harvested from patients with very late stent thrombosis and those with acute coronary syndrome unrelated to stent thrombosis are histologically indistinguishable from each other. Disruption of neoatherosclerosis inside BMS may be an important underlying mechanism of very late stent thrombosis after 3 years of BMS implantation. The mechanism for VLST in DES on the other hand is largely inflammation at strut site.

     

    Balloon angioplasty was chosen in the patient because of its simplicity and reasonable cost. Balloon angioplasty was one off the earliest strategies used to treat ISR. Lumen enlargement results from stent expansion and tissue extrusion. During the procedure balloon to artery ratio of 1.1 : 1 is selected. Crucially the stenosed part is tackled rather than entire stented segment to prevent dissection or trauma. Some operators use only non compliant balloons.

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    Against the background that transcathere aortic valve replacement (TAVR) carries similar risk of mortality as compared to surgical valve replacement (SAVR) in patients of severe aortic stenosis with a high risk score, the PARTNER 2 trial randomized a little more than 2000 patients of severe symptomatic aortic stenosis with intermediate risk to TAVR and SAVR. Intermediate risk was an STS score between 4% and 8%. About 75% of patients in the TAVR group underwent the procedure by the femoral access route while 25% had TAVR done by thoracic access.

     

    At 2 years the primary endpoint of death and disabling stroke was similar in both groups. Surgical aortic valve replacement was associated with less major vascular complications and paravalvular aortic regurgitation. TAVR on the other hand was associated with fewer episodes of atrial fibrillation, lesser need for blood transfusion and kidney replacement therapy. At 2 years the Kaplan Meier curve for death and stroke was about 20% in both groups. There were fewer deaths and strokes with femoral access TAVR as compared to SAVR, while death and stroke were the same when thoracic access TAVR was done as compared to SAVR. TAVR resulted in larger aortic valve areas. Half of the patients in PARTNER 2 trial were females, the average age was 81 years, and the mean STS score was 5.8.

     

    The researchers pointed out certain limitations. First there was a higher rate of withdrawal of patients from the surgical cohort. The valve used in Partner 2 was the Sapien XT which has now been replaced by the Sapien 3 balloon catheter device. Durability of the bio prosthetic valve is still to be ascertained over 10 years but at 5 years the TAVR valve has been found to be sturdy without signs of degeneration. Also multislice computed tomography imaging was not used consistently to assess aortic annulus dimension.

     

    NEJM MARCH 17, 2017

     

    The other large randomised trial comparing TAVR with SAVR was SURTAVI that included more than 1700 patients of severe symptomatic aortic stenosis with intermediate surgical risk. The mean STS score was 4.5. Severe aortic valvular stenosis was defined as valve area of 1 cm2 or less or valve area index of 0.6 cm2/ m2 and mean gradient greater than 40 mm Hg or velocity across aortic valve more than 4 m/ second. At 2 years the primary end point of death and stroke was similar in TAVR and SAVR , about 14% in both groups. The TAVR valve employers was the Core-Valve bioprosthesis. Surgery was associated with higher incidence of acute kidney injury,blood transfusion, and atrial fibrillation. Permanent pacemaker implantation and paravalvular regurgitation were greater in the TAVR group.

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    Dabigatran a direct thrombin inhibitor came into reckoning with the RELY trial published in the New England Journal of Medicine in 2009. More than 18000 patients of atrial fibrillation with increased risk for stroke were randomized to receive 110 mg or 150 mg of dabigatran twice a day in blinded fashion compared with warfarin adjusted to therapeutic INR in the remaining cohort. Warfarin, a vitamin K antagonist, has been used as an effective anticoagulant for decades. Warfarin reduces the risks of stroke by two thirds in patients with atrial fibrillation. Atrial fibrillation is the commonest sustained arrhythmia in the world, leading to stroke, systemic embolism, heart failure, ventricular arrhythmia and death. Warfarin however has been a hard task master, it has a bad efficacy/ risk ratio, tricky interactions with drugs and food, wide ranging blood level necessitating frequent blood monitoring. Apart from dabigatran the other non vitamin K antagonist oral anticoagulants (NOAC’s) available in the market are the direct factor Xa inhibitors, apixabn, rivaroxaban and edoxaban.

     

    Dabigatran was launched with the promise that it did not have the awkward baggage that accompanied warfarin. It had a small half life of 12-18 hours, reacted little with food or other drugs, and above all did not need any monitoring. The primary outcome of stroke and systemic embolism was, at the end of 2 years, 1.7% with warfarin, 1.5% with 110 mg dabigatran and 1% with 150 mg of dabigatran. Major bleeds were 3.7% with warfarin, 3.1% with 150 mg dabigatran and 2.7% with 110 mg dabigatran. Haemorrhagic stroke were 0.4% with warfarin, and about 0.1% with both doses of dabigatran( significantly less). Mortality was 4.3% with warfarin, and around 3.7% with both dabigatran groups. In patients with atrial fibrillation, dabigatran at 110 mg twice a day had similar rates of stroke and systemic embolism but lower risk of major haemorrhage. On the other hand the 150 mg twice a dose of dabigatran had significantly fewer stroke and systemic embolism but at equivalent rate of major haemorrhage.

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    The occasion was the Annual meeting of the Cardiological Society of India ( CSI ; Delhi , and I had been entrusted with the job of debating that “Aggressive treatment in hypertension had Abundant Evidence.” I had to speak against the motion and was quite convinced that the work cut out for me would not be too much of a bother. I however had not anticipated the turn of events that were to unfold in the hall. To begin with strangely nowadays the Annual CSI does not seem to attract the cardiologists or physicians of Delhi. They would come in droves in the eighties and ninetees One would expect with 3 leading institutions of the country offering a doctor in medicine (DM) degree in cardiology there would be senior residents in cardiology attending the Meeting. Maybe cardiologist in training in Delhi do not consider the annual CSI meeting worthy of providing any additional knowledge to what they already possess. In out times the teaching faculty of G B Pant Hospital, New Delhi insisted that we attend these meetings to fill up on our rather scanty knowledge of cardiology. Similarly residents of the All India Institute of Medical Sciences to were nudged to make sure they got around to attend bits and pieces of the conference, duties permitting. Currently apart from the 3 large teaching hospitals , other institutions in Delhi provide DNB cardiology courses, but I doubt if there was single one of the fellows in attendance.

     

     

    There were far more empty seats in the auditorium of a swanky 5 star hotel in the heart of Delhi than those that were occupied. Your shoulders do slump a bit with you face an empty hall. The effort put in making a talk can be considerable and especially so when gathering relevant data for a fiery debate. I was quite conscious of the emptiness in the hall as I got up to speak but worse was to come. I have always prepared my slide presentation on “Keynote”, which is an Apple Mac product. I carry it on my iPad, while earlier many years ago I would attend these meetings with my MacBook. The iPad is connected by a VGA adaptor to an HDMI cable that goes on to the projector. I possess a VGA adaptor and all these years the HDMI cable that costs from Rupees four hundred to five hundred only is provided by the projection team hired by the organisers of the meeting.

     

     

    To my horror I realised when I was standing right there at the podium that the chaps did not have the required cable to connect my iPad with my much laboured presentation. I was at a complete loss of words, I realised there was no way that I could now show my slides. My presentation had been shattered and I could not do d thing about it. What a waste. This was the Annual Delhi Cardiology Meeting without a Rupees five hundred cable. The projection personal and the young woman in charge appeared to have never heard of Apple, or of an iPad.

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  12.  

    LANCET PUBLISHED ONLINE ON 21st FEBRUARY 2018

     

    A recent review and meta analysis of 522 randomized trials that included almost 117,000 participants suffering depression, has concluded that all antidepressants are better than a dummy tablet. For decades doctors have been debating about the effectiveness of anti depressant pills in the treatment of depression.Twenty one types of antidepressants were studied as compared with placebo or head to head. In total a little more than 87,000 participants were assigned to an antidepressant, while 29,425 were assigned to a placebo. The mean age of participants was 44 years, 62% were women, and the median duration of acute treatment was only 8 weeks. The bulk of patients included in the meta analysis was from North America (48%), 27% were from Europe, while only 7% of patients were from Asia. Amitryptaline was the most effective anti depressant as compared to placebo, while newer anti depressants such as fluoxetine and sertraline were least effective .

     

    Almost 20% of the world population suffers from psychiatric problems and the majority of these have major depression. The extent of the problem can be gauged by the fact that the US is compelled to spend more than 200 billion $ for the management of depression. This meta analysis has been performed by researchers in Oxford university and has predictably taken the western print media by a storm, every major British daily has prominently displayed the study. The Guardian has gone to the extent of stating the that it’s now official that antidepressants work, its no longer some conspiracy by Big Pharma. The London Times has gone completely over the top by suggesting a million more people need antidepressants based on data provided by this meta analysis.What is however missed is that the authors of the paper concede almost in the beginning of their discussion that effects of the antidepressants were mostly modest, albeit more effective that placebo. Crucially it is also conceded by the authors that non industry funded trials were few in their meta analysis and also that many trials included did not divulge details of funding. The authors acknowledge that despite attempts at obtaining unpublished data, they are “aware a substantial amount of data is still not available to the public.”

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    We have all grown up being drilled that a dog is man’s best friend. My favourite quotes are from Marlyn Monroe “Dogs never bite. Just humans” and Charles de Gaulle , “The better I get to know men, the more I find myself loving dogs.” The latter never had to deal with the chaps running Allengers, a company that deals among other things with producing and installing cathetrisation laboratories. A catheterisation laboratory provides requisite imaging to safely perform percutaneous coronary interventions such as percutaneous coronary angioplasty and coronary stenting. You could also implant temporary and permanent pacemakers, ICD’s and biventricular pacemakers. These are all life saving procedures. The best catheterisation laboratories are supposed to be manufactured by Seimens and Philips, but I regretfully had opted for Allengers, an Indian company, much before the prime minister came up with the’ Make in India ‘ slogan, I had somehow been lured into believing indian personnel could be more considerate than a Dutch or German corporate manager. Let me assure you Allengers has proved to be merciless beyond the pale; the merchant of Venice would come out as a 4 weeks baby compared to the mandarins in Allengers. Shylock had infamously uttered “ I’ll have my bond. Speak not against my bond. I have sworn an oath that I will have my bond.” Shylock wanted his pound of flesh above everything else, even after the magistrate had offered him thrice the amount of money he was owed. But enough about Allengers, the story is for another day.

     

    IMG_6728

     

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    IMG_6667

     

    As the flu epidemic tightens its grip both in the U.K. and the US it is abundantly clear to scientists that the predominant culprit is the H3N2 subtype influenza A virus. The H3N2 virus subtype is disliked by physicians because it is far more potent than the other A and B influenza virus. H3N2 is capable of rapid transformation to elude the immune system of the human body. It is also associated with more severe symptoms, hospitalisation and death. The other troublesome fact is that vaccination against the H3N2 subtype is feeble, in fact influenza vaccination has been found to be effective for prevention in only 10% of people over 60 years. Vaccines against measles provide 97% protection and over 90% protection against small pox and polio. In short the flu vaccine is far from perfect. Currently more than 6% of people visiting outpatient departments of hospitals in the US are suffering from flu like symptoms, significantly greater numbers than previous years.

     

     

    IMG_6670

    New York Times 26/1/2018

     

    People with mild symptoms are best managed at home with lots of oral fluids and rest. In case symptoms are severe, or the elderly, or people with chronic disease such as diabetes, asthma, chronic heart disease, treatment may be initiated with Tamiflu within 2 days of symptom onset. Tamiflu does not reduce mortality but may reduce duration and severity of symptoms. Pregnant women with flu are considered high risk for complications. People down with flu are advised to wash hands frequently with soap, isolate tooth brushes and wash their bed sheets/pillow covers every third day. Recovery from flu usually takes 5-7 days. Antibacterial wipes should be used to wipe remotes, switches and door knobs. The British Medical Journal had warned that oseltamivir or tamiflu was no better than paracetamol in patients with flu, but research by the London school of hygiene and tropical medicine reported that tamiflu significantly cuts incidence of serious complications such as pneumonia. This report a meta analysis for whatever it was worth got published in the Lancet. Crucially tamiflu can cause nausea and vomiting, worse it has been reported that 8 Japanese children committed suicide after taking tamiflu.

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    The United States is currently  in the grip of a flu epidemic with a100 people already reported dead. The flu vaccine seems largely ineffective and there is the grim probability of more mortality. The strain is the same as the “Aussie Flu” H3N2 that acts within hours. You could me normal in the morning and down by evening, have pneumonia the next day. Experts believe this is the same virus that killed more than 50 million people in the Spanish Flu epidemic of 1918. Mortality will definitely be much less this time around because of significantly improved medical care. Tamiflu however is running out of stock in the US. The same virus has decscended in the United Kingdom. England will be hit by an epidemic in a couple of weeks. Around 120 people have already died in the U.K, where predominantly the culprit strain is influenza B ( B Yamagata or the Japanese Flu). The trivalent flu vaccine is ineffective against Japanese flu.The  developing furore over lack of efficacy of the vaccine is likely to  submerge findings of 2 recent trials that suggest clopidogrel may be as effective as ticagrelor despite guidelines recommending that  ticagrelor or prasugrel combined with aspirin be preferred to clopidogrel plus aspirin for at least a year subsequent to a percutaneous coronary intervention (PCI) in patients of acute coronary syndrome ( ACS). Both ticagrelor and prasugrel are more powerful anti platelet agents albeit associated with significantly greater bleeding.

    IMG_6634
    The TOPIC trial randomised 646 ACS patients to ticagrelor or prasugrel plus aspirin ( 323 patients)and after one month to clopidogrel plus aspirin (323 patients) post PCI. More than 90 % received a drug eluding stent and almost all patients were treated by the radial route. After one year the patients who were switched to clopidogrel plus aspirin had more than 50% reduction in the combined clinical end point of death, urgent revascularisation, stroke or bleed ( from 26% to 13%). There was no difference in ischemic events (11.5% versus 9.3%), while bleeding was substantially more in patients assigned to ticagrelor or prasugrel plus aspirin as compared to clopidogrel plus aspirin (15% versus 4%). The researchers explained their findings by the clinical observation that stent thrombosis is commoner in the first few weeks and months and that as time passes bleeding becomes a greater concern with ticagrelor or prasugrel. Switching to clopidogrel with aspirin after the first 4 weeks seems a reasonable clinical option as ischemic events are equivalent with the bonus of reduced bleeds.

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