Dispense As Written

The new 2026 ACC/AHA Dyslipidemia Guideline issued a Class 1 Recommendation for every adult in the US to get their Lipoprotein(a) measured once in a lifetime.

But here is the catch: if you find it elevated, the guideline’s core recommendation is simply to optimize modifiable risk factors—the exact same care we should already be providing.

With no completed outcomes trials yet proving that lowering Lp(a) reduces major cardiovascular events, this leaves primary care clinicians in a fascinating spot. Is this universal screening push brilliant proactive medicine, or is it market priming for an incoming class of therapeutics?

In Part 3 of our critical appraisal series, we look at 30 years of data from the landmark Women's Health Study to separate the medicine from the marketing.

📺 Watch the full appraisal here: www.youtube.com/@DispenseAsWritten

#EvidenceBasedMedicine #PrimaryCare #InternalMedicine #MedEd #Cardiology #LpaScreening

The 2026 ACC/AHA Dyslipidemia Guideline sets LDL targets of less than 70 mg/dL for high-risk patients and less than 55 mg/dL for very high-risk patients. Those numbers will drive prescribing decisions for the next decade.Has anyone ever run a randomized trial where one group was treated to a target of 70 and another to 55, and compared what happened? When the guideline was published on March 13, 2026 — no. Two weeks later, a trial called Ez-PAVE changed that.

In this episode, we go trial by trial through IMPROVE-IT, FOURIER, ODYSSEY OUTCOMES, and ORION — examining what each one actually showed — and what the guideline committee used to justify LDL thresholds that were never prospectively tested as targets.

Key Findings:

IMPROVE-IT: ARR 2.0%, HR 0.936 (CI 0.89–0.99); all-cause mortality HR 0.99; CV mortality HR 1.00; background statin was simvastatin 40mg — moderate intensity

FOURIER: HR 0.85, no mortality benefit (CV death HR 1.05, all-cause HR 1.04); median follow-up 2.2 years; NNT 74 over 2 years at ~$14,000/year

ODYSSEY OUTCOMES: All-cause mortality HR 0.85 is nominal — hierarchical testing stopped before it was formally tested; benefit concentrated in LDL ≥100 post-hoc subgroup; NNT 163 for mortality in full population

ORION: Primary endpoints are LDL surrogates only — no cardiovascular outcomes data; received COR 2a in the guideline anyway

Ez-PAVE (NEJM, March 28, 2026): First head-to-head target trial — open-label, 17 sites in South Korea, no mortality signal, published 15 days after the guideline

Castelli Coefficient: 5.5/10

Sources:Cannon CP et al. N Engl J Med. 2015;372:2387. DOI: 10.1056/NEJMoa1410489Sabatine MS et al. N Engl J Med. 2017;376:1713. DOI: 10.1056/NEJMoa1615664Schwartz GG et al. N Engl J Med. 2018;379:2097. DOI: 10.1056/NEJMoa1801174Ray KK et al. N Engl J Med. 2020;382:1507. DOI: 10.1056/NEJMoa1912387Lee YJ et al. N Engl J Med. 2026. DOI: 10.1056/NEJMoa2600283 (Ez-PAVE)Blumenthal RS et al. 2026 ACC/AHA Dyslipidemia Guideline. March 13, 2026.

Gregory Castelli, PharmD, FCCP, BCPS, BC-ADM, CDCESAssociate Professor | Director of Academic and Clinical PharmacyDispense As Written, LLC🎙️ YouTube: @dispenseaswritten📸 Instagram/TikTok: @gregcastellipharmd🐦 X/Twitter: @gregcastellirx📧 [email protected]

LEGAL DISCLAIMER: This content is produced by Dispense As Written, LLC and is intended for educational purposes for healthcare professionals. It does not constitute medical advice and should not be used to guide individual patient care. Always consult current clinical guidelines and use professional judgment in clinical decision-making. Dispense As Written, LLC operates independently of Gregory Castelli's academic and institutional roles.#DispenseAsWritten #EvidenceBasedMedicine #EBM #MedEd #PrimaryCare #FamilyMedicine #InternalMedicine #Dyslipidemia #ldlcholesterol

The newly released 2026 ACC/AHA Dyslipidemia Guideline represents a massive collaborative effort across eleven co-signing societies, introducing critical updates like new LDL targets and universal Lp(a) screening. It is a vital playbook for primary care.However, implementing these updates effectively requires us to look closely at how recommendations are categorized.As clinicians, it is easy to look at a Class of Recommendation 1 (COR 1) and treat it as a mandate backed by definitive randomized controlled trial (RCT) evidence. But the guidelines themselves are transparent that COR 1 can also be applied to areas guided primarily by expert consensus (LOE C-EO) or limited data (LOE C-LD) when trials aren't feasible.In my latest episode, I break down why understanding this distinction is essential for tailored patient care.The Methodology: The structural difference between COR 1 backed by RCTs versus expert opinion.The Primary Care Lens: How to translate specialized guideline frameworks into daily, real-world primary care practice.A truly comprehensive critical appraisal means understanding both the strength of a recommendation and the nature of the data supporting it.Discussion for the community: How do you balance strong guideline recommendations with expert-consensus levels of evidence when discussing treatment plans with your patients?#InternalMedicine #PrimaryCare #Cardiology #EvidenceBasedMedicine #MedEd #Dyslipidemia2026 #familymedicine #dispenseaswritten

Nearly 20 years after HPV vaccines were introduced, fewer than one in three eligible adolescent girls worldwide has ever been vaccinated. The barrier isn’t the science — it’s supply, access, and multi-dose schedules. If a single shot delivers the same protection as two, the public health implications are enormous.The ESCUDDO trial (Kreimer et al., NEJM 2025) enrolled over 20,000 girls across Costa Rica, randomized them to one or two doses of either the bivalent or nonavalent HPV vaccine, and followed them for five years. One dose was noninferior to two doses for both vaccines, with greater than 97% effectiveness against persistent HPV 16/18 infection. In this episode, I walk through the design, the noninferiority results, the nuances worth knowing, and — as always — why it didn’t score a perfect 10.━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━📊 KEY FINDINGS→ 1 dose noninferior to 2 doses for both bivalent (Cervarix) and nonavalent (Gardasil 9) → Vaccine effectiveness ≥97% against persistent HPV 16/18 in all four groups — effectively identical across one- and two-dose arms→ Rate difference (nonavalent): +0.21 infections/100 (95% CI −0.09 to 0.51) — upper bound well inside the 1.25/100 noninferiority margin→ Bivalent cross-protection against HPV 31: 38% with 1 dose vs. 83% with 2 doses — secondary finding, doesn’t change the headline, but clinically worth knowing→ Safety: 7 serious adverse events possibly related to vaccination out of 20,330 participants — no pattern, no signal📊 Castelli Coefficient: 8/10━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━🔗 LINKS & RESOURCESFull paper (NEJM): https://doi.org/10.1056/NEJMoa2506765ClinicalTrials.gov: NCT03180034Full citation: Kreimer AR, Porras C, Liu D, et al. Noninferiority of One HPV Vaccine Dose to Two Doses. N Engl J Med. 2025;393:2421-33. DOI: 10.1056/NEJMoa2506765━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━⚕️ ABOUT DISPENSE AS WRITTENEvidence-based medicine without the fluff. Every video ends with the Castelli Coefficient — a verdict that incorporates study design, statistical validity, and clinical applicability. No pharmaceutical sponsorships. No conflicts of interest. Just the data.Gregory Castelli, PharmD, FCCP, BCPS, BC-ADM, CDCESAssociate Professor | Evidence-Based Medicine EducatorYouTube: @dispenseaswrittenInstagram / TikTok: @gregcastellipharmdX / Twitter: @gregcastellirxEmail: [email protected]━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━⚠️ LEGAL DISCLAIMERThe content provided in this video is for educational and informational purposes only. It is intended for healthcare professionals and medical students as a supplement to — not a substitute for — clinical judgment, professional training, and the individualized care of patients.Nothing in this video constitutes medical advice, and it should not be used as the basis for any clinical decision regarding an individual patient. Always consult current clinical guidelines, institutional protocols, and your own clinical judgment when making treatment decisions.Gregory Castelli, PharmD, is speaking in his personal capacity as an educator. The views expressed do not represent the official positions of any institution or affiliated organization.This channel has no affiliation with, and has received no funding or compensation from, any pharmaceutical manufacturer, device company, insurance company, or other commercial entity with a financial interest in the content discussed.Use of trade names is for identification purposes only and does not constitute endorsement.━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━#DispenseAsWritten #EvidenceBasedMedicine #EBM #MedEd #PrimaryCare #FamilyMedicine #InternalMedicine #PharmD

Should I stop drinking coffee? For years, we’ve said yes — or at least probably. But that advice was built on zero randomized evidence. Observational data had been leaning the other way for years. Nobody actually ran the trial.Until now. The DECAF trial — Does Eliminating Coffee Avoid Fibrillation? — is the first randomized clinical trial to directly test caffeine in AFib patients after cardioversion. 200 patients. 5 hospitals across the US, Canada, and Australia. 6 months of follow-up. The coffee group had 47% recurrence. The abstinence group: 64%. Hazard ratio 0.61. That’s a 39% lower risk of recurrence with p = 0.01.This video walks through the PICO, study design, key demographics, results, adverse events, and what it means for how you counsel patients starting today.━━━━━━━━━━━━━━━━━━━━━━━━━━━━⚕️ CLINICAL TAKEAWAY• Stop routinely advising caffeine restriction in AFib patients after cardioversion• If a patient reports coffee as a personal trigger, that’s a different conversation — but it’s the exception, not the rule• This applies to naturally occurring caffeine at normal intake levels. Do not extrapolate to energy drinks or high-dose synthetic caffeine• Paroxysmal AFib was not studied — findings are specific to persistent AFib after cardioversion━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━🔗 LINKS & RESOURCESFull paper: Wong CX et al. Caffeinated Coffee Consumption or Abstinence to Reduce Atrial Fibrillation: The DECAF Randomized Clinical Trial. JAMA. 2026;335(4):317–325. DOI: 10.1001/jama.2025.21056ClinicalTrials.gov: NCT05121519⚕️ ABOUT DISPENSE AS WRITTENEvidence-based medicine without the fluff. Every video ends with the Castelli Coefficient — a verdict that incorporates study design, statistical validity, and clinical applicability. No pharmaceutical sponsorships. No conflicts of interest. Just the data.Gregory Castelli, PharmD, FCCP, BCPS, BC-ADM, CDCESAssociate Professor,Editor-in-Chief, PURL (Primary care Updates in Research and Literature) Series

📱 FIND USYouTube: @dispenseaswrittenInstagram / TikTok: @gregcastellipharmdX / Twitter: @gregcastellirxEmail: [email protected]━━━━━━━━━━━━━━━━━━━━━━━━━━━━⚠️ LEGAL DISCLAIMERThe content provided in this video is for educational and informational purposes only. It is intended for healthcare professionals and medical students as a supplement to — not a substitute for — clinical judgment, professional training, and the individualized care of patients.Nothing in this video constitutes medical advice, and it should not be used as the basis for any clinical decision regarding an individual patient. Always consult current clinical guidelines, institutional protocols, and your own clinical judgment when making treatment decisions.Gregory Castelli, PharmD, is speaking in his personal capacity as an educator. The views expressed do not represent the official positions of the University of Pittsburgh, its School of Medicine, or any affiliated institution.This channel has no affiliation with, and has received no funding or compensation from, any pharmaceutical manufacturer, device company, insurance company, or other commercial entity with a financial interest in the content discussed.Use of trade names is for identification purposes only and does not constitute endorsement.━━━━━━━━━━━━━━━━━━━━━━━━━━━━#AFib #DECAF #cardioversion #cardiology #EBM #primarycare #familymedicine #internalmedicine #medicaleducation #dispenseAsWritten #CastelliCoefficient

Your patient is still not at blood pressure goal after 1–3 months on a medication. Do you double the current dose — or add a second drug? Most clinicians double the dose. A 2025 Lancet meta-analysis of 484 double-blind, placebo-controlled randomized controlled trials has a definitive answer. And the math is not close.Doubling the dose buys you ~1.5 mmHg on average. Beta-blockers? Half a millimeter. Adding a second drug class at standard dose gets you ~6 mmHg more. That is a 4× difference. This video walks through the key findings — including a live demo of the free online calculator at bpmodel.org — and gives you a practical intensity framework to use in clinic today.━━━━━━━━━━━━━━━━━━━━━━━━━━━━📊 KEY FINDINGS• Standard-dose monotherapy lowers SBP by 8.7 mmHg on average across all classes• 79% of standard-dose monotherapies classify as low intensity (10 mmHg)• Thiazide diuretics are the only class that consistently clears moderate intensity at standard dose (10.8 mmHg)• Doubling the dose adds only ~1.5 mmHg — below the noise floor of office BP measurement• Adding a second drug class at standard dose: 14.9 mmHg — nearly double the effect of monotherapy• A second drug class is ~4× more effective than dose escalation━━━━━━━━━━━━━━━━━━━━━━━━━━━━🔢 STANDARD DOSES REFERENCED IN THIS VIDEO• Lisinopril 10 mg · Losartan 50 mg · Valsartan 80 mg• HCTZ 25 mg · Metoprolol 100 mg · Amlodipine 5 mg━━━━━━━━━━━━━━━━━━━━━━━━━━━━🔗 LINKS & RESOURCESFree BP combination calculator: https://www.bpmodel.orgFull paper: Wang N et al. Blood pressure-lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials. Lancet 2025;406:915–925. DOI: 10.1016/S0140-6736(25)01121-5

LEGAL DISCLAIMERThe content provided in this video is for educational and informational purposes only. It is intended for healthcare professionals and medical students as a supplement to — not a substitute for — clinical judgment, professional training, and the individualized care of patients.Nothing in this video constitutes medical advice, and it should not be used as the basis for any clinical decision regarding an individual patient. Always consult current clinical guidelines, institutional protocols, and your own clinical judgment when making treatment decisions.Gregory Castelli, PharmD, is speaking in his personal capacity as an educator. The views expressed do not represent the official positions of the University of Pittsburgh, its School of Medicine, or any affiliated institution.This channel has no affiliation with, and has received no funding or compensation from, any pharmaceutical manufacturer, device company, insurance company, or other commercial entity with a financial interest in the content discussed.Use of trade names is for identification purposes only and does not constitute endorsement.━━━━━━━━━━━━━━━━━━━━━━━━━━━━#hypertension #primarycare #familymedicine #internalmedicine #evidencebasedmedicine #EBM #cardiology #medicalducation #dispenseAsWritten

Title: Tirzepatide vs Semaglutide: Which GLP-1 Wins? | SURMOUNT-5 TrialDescription:Head-to-head comparison: tirzepatide 15mg vs semaglutide 2.4mg for weight loss. SURMOUNT-5 trial breakdown in under 5 minutes. Evidence-based medicine, no fluff.📊 KEY FINDINGS:Tirzepatide: -20.2% weight loss at 72 weeksSemaglutide: -13.7% weight loss at 72 weeks48.4% vs 27.3% achieving ≥20% weight lossSimilar tolerability (6.1% vs 8.0% discontinuations)Tirzepatide superior for weight reduction📚 CITATION:Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393:26-36.DOI: 10.1056/NEJMoa2416394🎓 ABOUT:Gregory Castelli, PharmD, FCCP, BCPS, BC-ADM, CDCESAssociate ProfessorDirector of Academic and Clinical PharmacyEditor-in-Chief, PURL SeriesDispense As Written delivers evidence-based medicine for busy clinicians—without the fluff.