ESC congress is perhaps the world largest (or at least one of the largest) gathering of cardiologists, over 30,000 delegates from all over the continent thronged the convention centre in Rome (Fiera di Roma)
MANY ‘NEGATIVE’ TRIALS, LOTS OF POSITIVISM FROM THE CONGRESS
Apology to those who were waiting for my synopsis on the recent European Society of Cardiology Congress Highlight. Due to overwhelming family and academic demand I had to delay writing up, indeed for long my blog has not been updated for similar reason, or rather excuses (at times!)
First of all I must declare that this was going to be one of the most memorable ESC congress, to me personally. One, because of the special venue, Rome. This was my first time in Rome. It is a city that is filled with history and reminiscent of thousands of years of civilisation, one of the very few places that was mentioned in the holy Quran (during the battle of Rome /Byzantine vs Persian), and the downfall of Constantinople that was once a capital of Roman/Byzantine by the famous Muhammad AlFateh army.
Beautiful historical landmark of ancient Roman civilization at the Coloseum. Beside this structure lie the Forum and Palatino, another two important marks of Roman history
The second reason, this was the longest ever time I have spent attending ESC congress, 9 days, yes, coz I left 3 days before the congress, flew to Kota Bharu to be an external examiner for Lincoln Universtiy 4th. Year Exam, flew back to KLIA 2 days later and immediately took the flight to Rome via Doha (Qatar Airways).
The third, an important reason, this was the first time our academic contribution in the form of abstract was accepted as a poster at the congress. Yes, nothing big about it, but it does give us hope as well as better idea how to make your presence felt in a European conference.
Highlight of our abstract – a study of high dose loading of statin drug in patients with acute coronary syndrome
The full title of the abstract: Efficacy and safety of high-dose rosuvastatin loading at emergency room before percutaneous coronary intervention among patients admitted with acute coronary syndrome, a pilot study authored by O. Maskon, KL. Koo, HH. Che Hassan, AZMI. Tamil, CHOOR. Chee Ken, RAFIZI. M Rus, SF. Mohamed, ISMAIL. M Saibon, D. Cumberland was presented by Dr. Hamat Hamdi.
This was a study done at HUKM, recruiting patients with acute coronary syndrome (heart attack), gave them a high loading dose of statin (cholesterol drug) which was rosuvastatin 40mg at the Emergency Department, just at the same time they are given aspirin and clopidogrel, followed by maintenance dose of 20mg daily. They were compared to standard treatment group, where the patients will be given statin in the ward, dose and type of statins up to to the discretion of the treating physician.
The hypothesis behind this trial was statin has pleiotrophic effect of reducing periprocedural myocardial infarction, or even reducing incidence of contrast induced myopathy among patients undergoing coronary angiogram or percutaneous revascularisation (PCI).
Though the short term result of the study was neutral, the strategy proved safe, and did reduce the LDL by 48% (ie potentially more patients can reach target goal of LDL cholesterol). There was also statistically significant improvement in the left ventricular ejection fraction in the treatment arm, which will have to be explored further in a larger scale trial.
Since latest guidelines advocate giving high dose statin in all patients with acute coronary syndrome, the study support the policy of early loading (and proved its safety), even before we know patient’s lipid status.
Our abstract – presented by Dr. Hamat Hamdi
NHAM President Dr. Ng Wai Kiat paid a visit at our poster.
Five new guidelines
The ESC Congress has become an ideal occassions for the ESC to promote their popularly known clinical practice guidelines. This year during the congress, five new guidelines covering Heart Failure, Atrial Fibrillation, CVD prevention, Dyslipidaemia and Cardio-Oncology were released.
Cardio-Oncology is interesting, as the guidelines told us that cardiovascular disease is one of the most frequent untoward events happening among cancer patients. As cardiologists we do frequently receive referral ranging from cardiotoxicity cases, arrhythmia or even acute coronary syndrome. They are a special group since the approach in treating them will differ, but now we are made aware, with this guidelines that they are a group that we should focus due to their added vulnerability. The aim of this guidelines is to prevent, optimize and treat those patients. Complications like cardiotoxicity (frequently in the form of cardiomyopathy, heart failure) from treatment can happen acutely, subacutely or even late. But then there are spectrum of other diseases such as arrhythmia (and QT prolongation), hypertension (can be as much as 45%!), coronary artery disease, arterial and venous thrombosis, valve and vasculopathy etc. There were also guidelines recommendation on how to do monitoring on patients receiving various potentially cardiotoxic chemotherapy. Echocardiography and other imaging such as MRI, biomarkers including highly sensitive troponins, natriuretic peptides (BNP/ProBNP) can be useful tools besides other routine cardiology tests.
There are four other guidelines. The Dyslipidaemia guidelines advocated total CVD risk estimation (European SCORE risk (a colourful chart used to determine one’s CVD risk based on gender, smoking status, blood pressure and total cholesterol level) as before and emphasised that certain factors may modify total risk SCORE including Lipoprotein (a), premature CVD/death, Family history (premature CVD/death) and recurrent events which will automatically place one into the very high risk group. It is recommended to do fasting sample, though a non-fasting sample may give similar prediction of risk for LDL and even Triglycerides, except in diabetics when the non-fasting LDL level could appear lower! The cut off LDL-cholesterol target points are: 1.8 mmol/l – very high risk (those with established CVD, CKD, diabetes with end organ or individuals with European SCORE risk); 2.6mmol/l for high risk group, and 3.0mmol/l for low or moderate risk group. They do advocate ‘maximally tolerated statin dose’ somewhat echoing the Americans high intensity statin in those of the high risk group patients.
Lipoprotein (a)? Is a kind of lipoprotein has some similarity with LDL, believed to be genetically linked and has added value in predicting risk in someone diagnosed with atherosclerotic disease.
Lowering the LDL is recommended using highest tolerated statin dose, how about non-statin role? Cholesterol absorption inhibitor Ezetemibe was given Class IIa recommendation as adjunct to lower LDL on top of statin, or when statin not tolerated. The newer agent, PCSK9 inhibitor (see later), may also be used as a last line or those not tolerating statin (Class IIb for now, awaiting result of outcome studies expected next year). Not to forget life style modifications and diet of course – avoiding trans fat, reducing total saturated fat and increasing dietary fibre etc.
A little note on triglyceride (TG) and (low) HDL. While recognising strong association of both TG and HDL with the risk of coronary artery disease (independent risk factor), the approach in treatment is less stringent comparing to that of LDL, the emphasis still on statin on top of lifestyle measure, and targetting the LDL. As for TG, a level of 2.3mmol/l is considered a treshold for treatment with a target level of 1.7mmol/l or below. No specific target of HDL is recommended, and though some general recommendations were given on approaches to raise HDL level, it was stated that thus far no conclusive evidence of benefit in raising HDL level per se.
Heart Failure as a preventable and treatable disease – so much that the new guideline in heart failure stands firm with this statement. It advised that in acute heart failure, efforts should be made to shorten time for diagnosis and therapeutic decision, allowing a faster delivery of beneficial treatment to patients. A faster decision time may be aided with the availability of biomarkers like natriuretic peptides (fast rule out of HF), and subsequently rule out cardiogenic shock and respiratory failure. The next step in the protocol is to spare time to rule out obvious underlying treatable cause of heart failure including by remembering the CHAMP acronym that stands for ‘Coronary’- Acute Coronary Syndrome, Hypertensive emergency, Arrhythmia, mechanical causes and pulmonary embolism. This should be followed by immediate initiation of specific treatment. After ascertaining the haemodynamic profile, presence of congestion and adequacy of peripheral perfusion is identified. Further stratifying patients by the level of systolic blood pressure, treatment with vasodilator and pressor agent/inotoropes are recommended. Other therapy including diuretic, vasodilator and mechanical support device including ultrafiltration. Regarding diuretic, Class IB given for the option of either direct bolus or slow infusion depending on patients response and symptoms.
Moving on to chronic HF, it is divided into three subclasses based on their left ventricular ejection fraction whether reduced, preserved or ‘mid-range’ – HFrEF (<40%), HPEF (>50%), HmrEF (40-49%). With regard HFrEF, Class I recommendation now given for all the three agents that are considered disease modifying or potentially improving prognosis – RAAS inhibitors (ACE Inhibitor or ARB), betablockers and mineralocorticoid receptor antagonist, means in any HFrEF, they should be given by default. The new agent, Angiotensin Receptor Neprilysin Inhibitor, Entresto (which showed an overwhelming positive outcome results announced 2 years ago) has now been given a Class I recommendation as replacement for an ACE-I to further reduce the risk of HF hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker and an MRA. While Ivabradin (If channel inhibitor) given IIa as an adjunct to betablocker to optimise heart rate, or alternative in those intolerant to betablockers.
Another revised guideline is on Atrial Fibrillation (AF). Why has AF attracted so much interest? It is a common condition affecting more than 30 million people worldwide, with 1 in every 4 middle-age people in Europe/US estimated to develop AF in their lifetime. It is estimated to be a causal factor of stroke in 20-30% of cases, and may be associated with a higher morbidity and mortality. There has also been rapid development in the area of rhythm control and anticoagulation. Therefore the guidelines cover acute and chronic management of rhythm/rate control, how to assess and manage stroke risk factors. The highlight includes newly approved stroke prevention OAC, edoxaban (high dose only). In essence rate control is the most important priority unless patients have significant symptoms despite optimal medication in which case ablation is recommended.
Therefore in atrial fibrillation early and simple risk stratification is the key. All valvular AF are still treated with the old warfarin, while non-valvular AF, based on CHA2DS2 Vasc score, may be treated with any of the NOAC or warfarin (all given class I indications equally). Low CHA2DS2 Vasc score of 1, given IIaB indication for OAC, while a score of 2 or higher Class IA. Left atrial appendage occluder such as the Watchman device may be considered in those patients with clear contraindication to OAC.
One may ask do the ESC taskforce have preference as to the types of OAC in general. With strong data on safety and efficacy of all the 4 NOAC, it’s no surprise that they are giving a Class I indication of prefering patients to be on NOAC instead of warfarin, providing no contraindication (well, mostly if the patient has mechanical valve, or significant mitral stenosis). No preference as to which NOAC is better, though. When warfarin is the choice, careful monitoring of INR (aiming highest TTR ratio) is mandated.
Tough battle of NOAC
Whichever of the NOAC is prescribed, the ESC guidelines in general seems to favour them in place of warfarin. An eyeball experience of walking through the exhibition booth during the Congress will immediately make one’s impression of the tough battle between the four NOAC, edoxaban being the newest player. So which one? Since the European are open to all four, it perhaps is more useful to know in brief what strenght do each have based on their clinical landmark trials.
Dabigatran being the first NOAC, it comes in two doses of 110mg and 150mg twice daily, it is a direct thrombin inhibitor, tested in RELY trial. Both doses effective compared to warfarin, the 150mg proved to have superiority in preventing ischaemic stroke.
Apixaban in a dose of 5mg twice daily, tested in ARISTOTLE trial (the only NOAC trial which my centre participated) showed improved all cause mortality when prescribed comparing to warfarin; besides its being the only NOAC that did not cause excess gastrointestinal bleed, and overall is perhaps the one NOAC that causes least bleeding.
Rivaroxaban, tested in ROCKET AF trial – unique since it was the only NOAC given once daily, 20mg being the standard dose. The population of ROCKET had the highest mean CHADS2 score comparing to all other NOAC trials (and highest rate of previous stroke), proven non inferior to warfarin in preventing stroke in AF patients.
Lastly Edoxaban, tested in a trial called ENGAGE. Its another of Factor Xa inhibitor, both doses of 30mg and 60mg proven non inferior to warfarin, and in addition showed superiority in reducing cardiovascular mortality comparing to warfarin. Of note, only the high dose of 60mg approved for AF prevention.
A small personal note, you notice all those NOAC have come up with catchy acronym for their trials….I sometimes imagined that the principal investigators for the NOAC trials pitched themselves against each other to create the most catchy names of their trials acronym (no, nothing like that, just a coincidence)…so that one who has difficulty remembering the trials could simply learn the following pnemonic…
What is the most reliable NOAC – the answer is Dabigatran (RELY); which NOAC do you give to old astronaut if he gets AF – rivaroxaban (ROCKET-AF); if a patient from Greece gets an AF which of the NOAC would he prefer? – answer apixaban (ARISTOTLE); and lastly if a young and single woman got an AF, which NOAC would you give her – edoxaban (ENGAGE).
All the NOAC consistently showed superior reduction of intracranial bleed (ICH) comparing to warfarin, all except apixaban seemed to cause excess gastrointestinal bleed. Dabigatran has the highest renal excretion therefore more caution needed in patients with renal failure. All of them are given twice daily except rivaroxaban which can be given once daily.
Their obvious advantage is not requiring INR monitoring and simple dosing regimen. Overall they are at least as effective as warfarin, simple to prescribe, better in reducing ICH bleed, less drug interaction or with food, therefore the obvious choice, of course provided patients can afford the high cost.
Now that all the above NOAC are available in the market (Edoxaban not yet in Malaysia) the question may arise as how to manage bleeding. The guidelines have clearly documented the prediction and management of bleeding. As regard antidote, dabigatran had come up with their idaruxizumab (Praxbind) which is an Fab antibody specifically binds to dabigatran – released last year. In this ESC congress, a data on new reversal agent for oral Xa inhibitor (all those xabans) called Andexanate alfa was presented, and proven to be effective in acute major bleed.
Hotline sessions – exploring evidences
In the field of AF, yup we are still not out of the wood, a registry from Norway called the Beyond program (involving over 35000 patiets) was presented. They looked at incidence of bleed among the three NOAC and warfarin, and concluded that apixaban and dabigatran were the two NOAC have lowest bleeding event including ICH, while dabigatran and rivaroxaban were found to do worse comparing to warfarin in term of causing excess GI bleed. No data on mortality or morbidity though, was available, and a brief look at the baseline data did show some dissimilarity among the groups, again this was a registry so must be interpreted with caution, and only a very general conclusion or impression can be drawn up. We shall await full data. Of note there had been several publications of ‘real world data’or evidences on the three NOAC proving their safety and efficacy respectively, some reassurance to all of us cardiologists who prescribe these new and expensive medications to our AF patients.
The was also a study of anticoagulation (warfarin) among cancer patients with AF, and this found similar risk and benefits of warfarin on AF patients with or without cancer; this provides reassurance some reassurance again, not to deprive those cancer patients from stroke prevention treatment when they are diagnosed with AF.
DANISH study conducted in Sweden, a large prospective study investigating the use of ICD among patients with non ischaemic dilated cardiomyopathy, found no survival benefits in the overall population. However, two other findings were noted, there was a survival benefit among the younger patients (below 68), and regarding death, the ICD did reduce incidence of sudden cardiac death (but not total mortality). This new finding called for revision to the guidelines of prophylactic ICD among patients with non-ischaemic cardiomyopathy (especially the older age group). It must be noted that, in this Swedish trial, all patients were treated with optimal medical therapy and 60% already on CRT (cardiac reshyncronization therapy), so they may be a slightly different subjects that we found in clinical practice.
Regarding these device treatments in heart failure, there are manufacturers who advocate the remote monitoring element in their ICD or CRT device when they are implanted among those eligible cardiomyopathy patients. The question is whether this sophisticated module brings any additional benefit? A trial called More-Care showed no additional benefit in clinial outcome (death, cardiac events), except some decrease in rehospitalisation.
Another research in cardiac regenerative therapy in advanced heart failure was presented, called CHART 1 trial comparing mesenchymal stem cells direct injection to myocardium (catheter based treatment) with control. This yielded a neutral result in term of clinical outcome. So we are still in search of firm evidence to support the use of regerative therapy in heart failure.
In the field of critical care, a registry data of patients surviving cardiac arrest in a large Danish population was presented. This showed several variables that favoured survival eg. Bystanders who are trained with cardiopulmonary resuscitation (CPR) skill, and a transfer to a cardiac centre with cardiac intervention facility both improve survival significantly. Unshockable rhythm, age, comorbidity were non-favourable factors for survival.
ECMO ongoing cardiac arrest metaanalysis looked at the 30 day survival among patients treated with the extracorporeal membrane oxygenation life support ECMO, which showed favourable trend of survival and improved neurological outcome comparing to control, or Intraaortic balloon pump (IABP), but not Impella or Tandemheart.
Among those comatose or mechanically intubated patients undergoing percutaneous intervention (PCI), one viable alternative of giving P2Y12 inhibitor as part of the dual antiplatelet (DAPT) strategy, is administering crushed ticagrelor, which was proven effective by measurement of the platelet reactivity testing. This would be a good alternative especially if you do not have access to other method of giving P2Y12 antiplatelet, such as cangrelor which can be administered intravenously.
Another classic landmark the Vatican City…I just managed to walk by the place. The enjoy the visit fully, entrance to the Museum is a must
New in Acute Coronary syndrome (ACS) and interventional cardiology
Among patients presenting with non-ST elevation MI ACS, those who have intermediate or high risk score are unfortunately getting less opportunity to invasive procedures such as coronary angiogram or PCI. This was shown by the large European GRACE registry. As a result, among this intermediate or high risk group, compared to those receiving the optimal care, those who didn’t, have a 1.7 times higher risk of mortality. This is a European observation (real world data), which we believe in our own setting, it is much more so, especially those patients with ACS who are of higher risk score, are typically patients with higher commorbidities like heart failure, renal or multiorgan failure which put them in a more complex situation and not feasible to subject them to interventional procedures.
Next in line is the antiplatelets trials. There were a few highlighted. ANTARCTIC, a study involving total over 900 patients (elderly) with ACS studied the value of platelet testing using Verifynow machine among patients given prasugrel 5mg daily for their post PCI. There were randomised 1:1 to control or monitoring group (group who was subjected to platelet reactivitiy testing). This monitoring group were further subdivided into three – those with suboptimal platelet suppression (PRU), given 10mg daily, those with normal value were maintained on 5mg while those with very low PRU (means very well suppressed platelet activities) were given clopidogrel 75mg daily. Final result – no significant difference between all the groups in term of clinical endpoint. Therefore, based on this trial, there is little value in monitoring for platelet reactivity in clinical practice.
Another trial called PRAGUE-18 compared ticagrelor vs prasugrel among patients with STEMI undergoing primary PCI. The trial failed to recruite targeted number of subjects and due to circumstances, a high number of dropout from both groups up to 30% (driven mainly by financial – converted to open clopidogrel) ended up with 367 patients maintained on ticagrelor and 458 patients on prasugrel to the end of study or death. The result: no significant difference in the primary endpoint of CV death, MI or stroke between the two groups. It was concluded that the study did not have enough power to draw firm conclusion on the safety or efficacy comparison between the two new P2Y12 antiplatelet.
Drug eluting stents (DES) vs Bare metal stents (BMS) still an ongoing debate? Sounds a bit odd when most interventionists these days are moving towards 100% DES practice in their daily PCI strategy (including primary/emergency PCI). A multicentre trial in Norway called NORSTENT recruited over 9000 patients undergoing PCI (stable CAD or ACS) and randomised the patients either receiving DES only or BMS only, followed up both groups for a mean up to 5 years. This is investigator recruited trial, over 95% of the DES used were of the 2nd generation or later such as Xience, Promus, Resolute compared with the latest BMS technology such as the new Driver, Integrity & Liberte stents. Surprise surprise, the result: No difference in the primary endpoint of death or MI; or all cause mortality. When revascularisation or stent thrombosis were compared, there was a significant difference (reduction) of absolute reduction 3.3% and 0.4% respectively favouring DES. This translate into nnt of 30 and 250 respectively in favour of DES. Caveat? While it is a largely robust conclusion of the ‘similarity’ in performance between DES and BMS, its probably nothing new to expect, ie the DES is not expected to give superiority over BMS in mortality nor MI reduction. However, the relatively low TLR rate among the BMS patients (6 year rate of 19.8%) is impressive for these new generation BMS.
So how do you interprete the above astounding result and apply it in clinical practice. First of all, looking at the inclusion criteria and the procedural characteristics in the trial one could almost make a conclusion that it is only in a ideal world that you can replicate such trial outcome in a real world practice. Of course the study did not involve any left main stenting, no complex bifurcation, no previous stenting, not a real multivessels PCI as proven by the low mean number of lesions per patient treated (1.4 lesions/patient) and only 1.7 stents/patient. A mere 6% of patients have multiple procedure/staged PCI. In a real world practice we are treating more complex lesions and multivessels disease involving bifurcations or even Left main (selected cases), these days the practice (to apply the recommendation) is to evaluate the SYNTAX score, a low SYNTAX score in a multivessel disease patient means potentially good outcome even with multivessels, multistent approach.
Nevertheless, the current study (which has been published in NEJM) does highlight the excellent performance of new bare metal stent technology and may still be applicable when economic situation demands (though, currently the cheapest DES costs as little as a BMS!)
Night time in Rome…at Trevi fountain
Night time walk around the city
Hypertension/risk factors and the value of prevention
A researcher from US presented a striking finding on the value of long term exposure to lower LDL and BP in CV outcome. Though it is not a randomised interventional study it threw an important concept that allows us to understand further why trials such as HOPE, HOPE 3 gave such an impressive CV outcome result by simply prescribing antihypertensive or/and statin to our patients. The trial is called NATURE’S RANDOMIZED TRIAL OF BLOOD PRESSURE AND CHOLESTEROL LOWERING. It is a long term population cohort study that involved over 100,000 people. They looked at several genetic scores that were associated with low LDL and low BP. What was presented, the presenter (B Ference) emphasised had nothing to do with genetic study, it was merely an observation on how low LDL and low BP population compared to those ‘normal’ones. To simplify the result, expressed in Odd Ratio term (simply the lower the ratio, the less the risk, and vice versa, 1 being the reference point). A low SBP (by 3mmHg) gave OR of 0.821, low LDL (by 12mg/dl) 0.758 and a low SBP combined with low LDL gave ones an OR of 0.542. In a simple term, means comparing to control, someone with 3mmHg lower SBP and 12mg/dl lower LDL will have 54% less chance of developing major vascular events. Extrapolating from this finding, a person with 1mmol/l lower LDL and 10mmHg lower SBP will have an odd ratio of 0.139 comparing to control. The conclusion: SBP and LDL-C have independent, multiplicative and cumulative effects on CVD risk.
While talking about low BP, many of us would have been aware of the result of intensive BP lowering in SPRINT trial which demonstrated favourable CV outcome with lowering of BP to 120/80mmHg. However, the commentator noted, the method of BP measurement in SPRINT was unique and perhaps not reproducible in daily practice – the so-called ‘unattended BP measurement’ the subjects were left in a quiet room to self measure BP. Therefore, in daily practice, the corresponding ‘SPRINT’ level SBP, or a more realistic reading is <130mmHg. CLARIFY was a study to investigate whether there is ‘J’curve effect of BP among patients diagnosed with stable ischaemic heart disease. The study found that the ideal BP for IHD patients were in the range of 130-139/70-79 mmHg (in contrast to SPRINT finding), this applied to all subgroups except in stroke patients (who would benefit from a lower BP).
The deleterious effect of sleep apnoea (OSA) is well known in worsening CV outcomes, and strong association with heart failure and hypertension. The Sleep Apnoea CV outcome study (SAVE) sought to determine if CPAP treatment of moderate to severe OSA in patients with CV disease would reduce the incidence of CV events. The Australian based study randomised over 3000 subjects with OSA to sham control or CPAP and followed them up to 7 years. There was no difference in primary endpoint – A composite of death from CV disease, CVA, or hospitalization for unstable angina, heart failure or TIA. Nevertheless CPAP significantly improved daytime alertness, mood, quality of life, and reduced work-days lost because of ill-health.
Dinner at a Halal restaurant in Terminal
Over the horizon, new and coming soon
I have elaborated a good bit on those new anticoagulants most of which are already being in the market in Malaysia since the last good 2-3 years. Edoxaban is perhaps coming soon though I haven’t heard of any development yet.
Any other new kid in the block? They may have been mentioned in last year’s highlight, but worth repeating since they are now coming up soon for clinical use.
Empagliflozin, an inhibitor of sodium-glucose cotransporter 2
(SGLT2) diabetic drug, had shown an impressive result of reduction in mortality and heart failure among patients with Type II diabetes (EMPAREG). Thus far no other drug of this class has produced similar result though trials are ongoing. The drug gives modest reduction in blood sugar and HbA1C. There had been a few sessions during this congress highligting the importance of this new finding. Is it a blockbuster drug? Well, so far, for any antidiabetic to be proven safe in diabetic patients is already a big challenge, leading to withdrawal of some of the drug classes due to unfavourable post marketing adverse events. However, the case was different with Empaglifazone, which surpassed the safety requirement and beyond, making it a potential cardiovascular protective drug for diabetics, who by default are at increased risk of CV events. What are the possible mechanism? Analysis of the study result showed there was a significant difference in the blood pressure in the Empagliflozin arm. Together with significant reduction in heart failure events, these two mechanisms could well be the positive attributes leading to its positive CV outcome result.
Not long before the Congress, we were pleased to hear the news on the result of LEADER trial – another diabetic drug called Liraglutide (Victoza – a glucagon-like peptide GLP-1 analog) which had similarly (though less profoundly) showed reduction in CV death among Type II diabetics.
Thus these two new diabetic drugs offer new hope in improving the prognosis in our Type II diabetic patients. The European and Canadian guidelines have incorporated recommendation on the use of Empagliflozin ‘to be considered’ in Type II diabetics in order to delay the onset of heart failure and prolong life.
Lower LDL? Thus far there hasn’t been a J curve phenomena such was found in hypertension study (ie no so-called low cut off point of LDL that could be dangerous, while evidence favouring lowering the level beyond 1.8mmol/l is growing, one recent one was from the IMPROVE IT study on statin/ezetimibe combination). There are three PCSK9 inhibitors currently undergoing phase III trial for clinical outcome result – Alirocumab (ODYSSEY OUTCOME), Alirocumab (FOURIER) and Bococizumab (SPIRE 2) to test safety and efficacy in high risk subjects aiming reduction of LDL beyond 1.8mmol/l. Evidence of safety has been accumulated now among the three agents, and last year a publication of ODYSSEY Long Term Trial in NEJM showed promising result of not only impressive LDL reduction (62%), there was also statistically significant difference in the CV events favouring Alirocumab (on top of statin combination) comparing to control. The European has made a proactive step of putting it into their recommendation as IIb (in combination with statin +- ezetimibe). Alirocumab is expected to be available in Malaysia soon, which opens up the horizon to further improve patient’s LDL level. Possible use including those with Familial hyperlipidaemia; secondary prevention in high CV risk patients whose LDL is suboptimal; and those statin intolerant patients.
This famous seafood restaurant that we visited twice…shhh I hope Tan Sri won’t tell anyone about the Pokemon thing…
Entresto to improve prognosis in heart failure
The new agent, Angiotensin Receptor Neprilysin Inhibitor, Entresto (landmark trial PARADIGM-HF published & presented 2 years ago, demonstrated significant reduction in total and CV death & hospitalization for heart failure – 16%, 20% & 21% absolute reduction comparing to standard treatment with ACE inhibitor) has now been given a Class I recommendation as replacement for an ACE-I to further reduce the risk of HF hospitalization and death in systolic heart failure patients who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker and an MRA. Keeping in mind, the drug it may be given to a naïve HF patient (reduced systolic function with symptomatic/high risk Class II or III NYHA) it has to be given during a stable phase (not during the acute heart failure/in patient treatment). Starting dose may be low among naïve patients – 50mg twice daily, to maximum of 200mg BD. Caution in patients with low BP, since in the trial a 100mmHg systolic BP cut off was used as safety requirement (95mmHg before randomisation).
Statement of Conflict of Interest: Lastly – this summary and highlight of the congress is purely my personal work the information which was gathered from the sessions as well as online materials from the Congress (ESC Congress 365). I attended the Congress under the sponsorship of Sanofi Malaysia, nevertheless I was under no obligation to represent any companies or authorities.