عبدالله الدخيل

Internal Medicine Resident @KFSHRC #QUMED38

[Pablo Corral MD @drpablocorral]

Lp(a)HORIZON is negative. Does this mean the Lp(a) hypothesis is wrong? I don’t think we can conclude that — at least not yet.

Before seeing the full data, several explanations deserve consideration:

1. Background therapy matters.
In contemporary secondary prevention, aggressive LDL-C/ApoB lowering and comprehensive risk-factor control may substantially reduce the residual risk attributable to Lp(a)

2. Perhaps we are treating too late.
Genetics reflects lifelong exposure to elevated Lp(a). Lowering Lp(a) for a few years after ASCVD is already established may simply be too little, too late

3. Magnitude and duration of Lp(a) lowering may matter.
Not all Lp(a)-lowering strategies are equivalent. We need the achieved absolute levels, sustained reduction, adherence, and exposure over time before extrapolating HORIZON to the entire therapeutic class

4. The benefit may lie in the extreme tail.
Perhaps the clinically modifiable risk is concentrated among patients with very high Lp(a). The prespecified analyses at higher baseline Lp(a) levels will be particularly important

5. Lp(a) concentration may not tell the whole biological story.
OxPL burden, apo(a) isoform size, and particle composition may influence pathogenicity. Two patients with the same Lp(a) concentration may not necessarily carry the same Lp(a)-mediated risk

6. Could the endpoint dilute the signal?
Lp(a) may preferentially affect coronary and recurrent events. Individual MI/revascularization and total-event analyses may tell a different story than first 4-point MACE.

7. Genetics may predict causality better than therapeutic effect size.
Mendelian randomization reflects decades of exposure. It should not automatically be translated into the magnitude of benefit expected from a relatively short pharmacological intervention

8. Are we targeting Lp(a), but not necessarily its most pathogenic cargo?
Lp(a) is the major carrier of oxidized phospholipids (OxPL), which contribute to vascular inflammation, plaque vulnerability and thrombogenicity. Lp(a) concentration may therefore be an imperfect surrogate for its biological activity. The relationship between Lp(a) lowering, OxPL reduction and clinical benefit deserves particular attention

9. Could intensive antiplatelet therapy attenuate the atherothrombotic component of Lp(a) risk?
Lp(a) may promote thrombosis through platelet activation, coagulation and formation of more lysis-resistant clots. OxPL can also interact with platelet receptors. In a secondary-prevention population such as HORIZON, where aspirin and other antiplatelet therapies are extensively used, part of this pathway may already be pharmacologically suppressed — potentially leaving less Lp(a)-mediated risk for pelacarsen to modify

10. Low event rates may be part of the answer.
Despite enrolling 8,323 high-risk secondary-prevention patients, HORIZON required a remarkably long follow-up to accrue the prespecified number of events. This suggests that contemporary secondary prevention substantially reduced the absolute residual risk available for Lp(a) lowering to modify. Nuestro análisis previo ya señalaba que la menor tasa de eventos era una de las principales amenazas para el estudio

11. Was HORIZON powered for a larger effect than the true pharmacological effect?
An event-driven design protects statistical power if the required number of events is reached — but only for the effect size assumed in the design. If short-term pharmacological Lp(a) lowering produces a much smaller benefit than predicted from lifelong genetic exposure, even a trial of >8,000 patients may struggle to demonstrate it

12. The long time required to reach the endpoint may itself be biologically informative.
These were patients with established ASCVD and very high Lp(a), yet events accumulated more slowly than anticipated. Perhaps elevated Lp(a) identifies substantial lifetime risk, but contributes less modifiable short-term residual risk once other major pathways are aggressively treated.

13. Six years is a long time for background therapy to evolve.
During prolonged follow-up, increasing use of PCSK9 inhibitors, ezetimibe, bempedoic acid, inclisiran, SGLT2 inhibitors and GLP-1 receptor agonists — together with improved BP and antithrombotic management — may have progressively reduced event rates in both groups. These potential therapeutic “drop-ins” were already a concern before the results were known

14. First events may not capture the entire Lp(a) burden.
Lp(a) could influence recurrent coronary events and total atherosclerotic burden more strongly than time-to-first MACE. Analyses of total/recurrent events will therefore be particularly important

15. The “risk-factor exhaustion” hypothesis.
With LDL-C around 65 mg/dL, intensive lipid-lowering therapy, antiplatelet treatment, good BP control and contemporary diabetes therapy, multiple atherogenic and thrombotic pathways were already being targeted. HORIZON may therefore have tested Lp(a) lowering in a setting where relatively little modifiable residual risk remained. The published baseline characteristics already showed how intensively treated this population was

16. Perhaps the effect of Lp(a) depends on the surrounding biological environment.
The clinical consequences of Lp(a) may result from the interaction of apoB particle burden + OxPL-mediated inflammation + thrombosis/impaired fibrinolysis. With LDL/ApoB aggressively lowered and most patients receiving antiplatelet therapy, two important components of that environment may already have been attenuated.

Maybe the key question is not simply whether Lp(a) is causal, but WHEN, in WHOM, and HOW MUCH it needs to be lowered to change clinical outcomes.
Until we see the full HORIZON dataset, declaring the Lp(a) hypothesis dead seems premature.

#Lp(a) #LipoproteinA #ASCVD #Cardiology #Atherosclerosis #Horizontes

https://t.co/4vg5My5m4b

[عبدالله الدخيل @aialdekhail]

For once in hematology, the softer option actually won. Who knew we didn’t always have to put the patient through hell to treat the leukaemia :)

[NEJM @NEJM]

Original Article: Azacitidine–Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia (PARADIGM trial) https://t.co/iiDNsw6CUW

Editorial: Hypomethylating Agents plus Venetoclax as Compared with Intensive Chemotherapy in Patients with AML https://t.co/zsAPQjxEDb

#Hematology

[د.ناجي علي الخليف MD, FACC, FRCPC @Nk385]

في خبر محلجل في عالم الكوليسترول وامراض القلب

اعلنت شركة نوفارتس فشل علاجهم الجديد Pelacarsen في تخفيض الاصابات بامراض القلب بالرغم من تخفيضه لمستوى Lp(a) الوراثي بمستويات عالية

توقع الكثيرون ويكادون يجزمون ان تخفيض هذا البروتين سينتج عنه تخفيض في عدد الاصابات بامراض القلب ولكن..

اعلنت الشركة غير ذلك وانضم هذا البروتين الى غيره من العلامات التي تخفيضها بالادوية لا ينتج عنه فائدة طبية مثل رفع HDL وتخفيض TG وغيرها

ويبقى بروتين LDL لوحده البروتين الاهم والذي بتخفيضه تهبط خطورة امراض القلب

هذا درس اخر للحذر من الانجراف خلف التوقعات قبل ظهور نتائج الدراسات السريرية المحكمة

لم تنتهي القصة بالكامل فمازالت هناك دراسات جارية لعلاجات اخرى في هذا المجال ولكن طريقها للنجاح اصبح اقل وضوحا

[عبدالله الدخيل @aialdekhail]

This question was answered nearly two decades ago:
https://t.co/8ymT62Ejk2
In patients with prior aspirin-associated ulcer bleeding, continuing aspirin with esomeprazole resulted in a recurrent ulcer bleeding rate of 0.7%, compared with 8.6% in those switched to clopidogrel alone

[د. عبدالله البيروتي @aalbeirutty]

مريض عنده قرحة في المعدة وسببت له نزيف، وبياخذ أسبرين بعد ما جاته جلطة في القلب قبل عدة شهور.

هل نقله يستمر على الاسبرين أو لا؟

[عبدالله الدخيل @aialdekhail]

Unbelievable!

Presented to ER with ACS > arrested > achieved ROSC after 10 min > cannulated for VA-ECMO, intubated, kept on inotropes > improved > support weaned-off, de-cannulated from ECMO and Extubated > discharged to complete his Hajj with a smart watch to follow his vitals.

[مدينـة المـلك عبـدالله الطبيـة @KAMC_MAKKAH]

#News | 🗞️

After complete cardiac arrest...

#King_Abdullah_Medical_City saves an Indian pilgrim using mobile cardiac ECMO technology, enabling him to continue his spiritual journey with smart health monitoring.

https://t.co/Iy4Wg9v0PI

#Healthy_Hajj
#Hajj_1447
#Makkah_City_of_the_Safe_Heart

[Ahmed Almustafa, MD, FACC, FHFSA @ahmedrm1]

Proud to announce the launch of the Advanced Heart Failure and Transplant Cardiology Fellowship Program at King Faisal Specialist Hospital & Research Centre, Riyadh.

The first fellowship of its kind in Saudi Arabia, officially accredited by the Saudi Commission for Health Specialties.

Established at a leading regional center in heart transplantation and mechanical circulatory support, the program is designed to train future leaders in this highly specialized field.

[عبدالله الدخيل @aialdekhail]

@GaneshMuthappan @SeeFisch In 1960s studies, patients were given at least 100 mg so everyone did the same since then.
But the new Aldactone formulations are more potent than older ones. So now it would make sense to start with 25 mg rather than 100.

Note: Japanese guidelines recommend starting with 25 mg.

[واس العلمي @SPA_sci]

أطباء سعوديون يحققون المركز الأول في مسابقة صحية ضمن فعاليات مؤتمر صحة قطر 2026.
https://t.co/svWu96igdb
#واس

[عبدالله الدخيل @aialdekhail]

1- No statically significant reduction when we see mortality alone, but only when it comes to the combined endpoint (Death/hospitalisation).

2- Wide CI that crosses 1 when it comes to the question of adding Digitoxin on the Quadruple therapy.

The trial needed a larger sample.

[ريان | MD1TALK🌟 @md1talk]

ال Digoxin رجع من الباب الكبير

من خلال اخوه اللي اسمه Digitoxin

دراسة جديدة اثبتت ان عنده mortality benfit في ال HFrEF

[عبدالله الدخيل @aialdekhail]

@AbdullahNHW إنا لله وإنا إليه راجعون،
الله يغفرلها ويرحمها ويسكنها فسيح جناته، أحسن الله عزاكم وعظم الله أجركم

[عبدالله الدخيل @aialdekhail]

An important trial that further shows that the American College of Cardiology blood pressure recommendation of targeting BP less than 130/80 is more superior to The American Academy of Family Physicians recommendation of targeting BP of less than 140/90.

[NEJM @NEJM]

In the BPROAD trial, patients with type 2 diabetes had a lower incidence of major cardiovascular outcomes with a systolic blood-pressure target of less than 120 mm Hg than with a target of less than 140 mm Hg. Full trial results and Research Summary: https://t.co/HrGBjmBr7A

[إبراهيم سرحان | Ibrahim Sarhan @sarhaniy]

أحد الأودية النائية في السعودية 📍🗺️
Remote valley in Saudi Arabia

[صالح القرني @Artist_Saleh]

لوحة قطة الرّس

ألوان زيتية على كتّان
160*120 سم

القطة التي استخدمها مقاومو الرس في صد محاولة ابراهيم باشا لتفجير سور الرّس.

ضمن اطلاق المجموعة الفنية الأولى ل(تخليد) - لتجسير الموروث عبر الفن @Takhleed_KSA

[عبدالله الدخيل @aialdekhail]

Moderate resuscitation is preferred in pancreatitis according to the WATERFALL trial that showed that aggressive resuscitation resulted in more volume overload without significant clinical outcome improvement.

“Moderate” here means 10 ml/kg bolus and 1.5 ml/kg maintenance.

[عَالَم طِبْ الَباطِنَة✨ @world_of_med1]

ايش أفضل محلول نستخدمه في
acute pancreatitis
و كم الrate
و هل نفضل نستخدم aggressive or moderate resuscitation ؟

[سلمان بن عبدالعزيز @KingSalman]

يومنا الوطني المجيد ذكرى عزيزة متجددة في صفحات الوطن الأبيّ، متجذرة في وجدان الشعب السعودي العظيم. اللهم أدم على بلادنا أمنها ورخاءها واستقرارها، واحفظها من كل سوء.

[عبدالله الدخيل @aialdekhail]

@ibraheemiyanda2 الله يبارك فيك دكتور

[عبدالله الدخيل @aialdekhail]

@FaisalAlnajm الله يبارك فيك فيصل

[عبدالله الدخيل @aialdekhail]

#Matching2024

اللهم لك الحمد حتى ترضى ولك الحمد إذا رضيت ولك الحمد بعد الرضا

قُبلت بفضل الله برغبتي الأولى في بورد الطب الباطني بمستشفى الملك فيصل التخصصي ومركز الأبحاث بالرياض.

[عبدالله الدخيل @aialdekhail]

@7adqah الله يبارك فيك دكتور علي

[عبدالله الدخيل @aialdekhail]

@AbdullahNHW الله يرفع قدرك أبو عابد

[عبدالله الدخيل @aialdekhail]

@khalid00ooo0 الله يبارك فيك دكتور خالد وعقبالكم بإذن الله