Sanjay Kaul @kaulcsmc Twitter profile

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Sanjay Kaul

@kaulcsmc

2 years

1/ My top trials, AHA 2022 1. TRANSFORM-HF: torsemide vs furosemide in hosp. HF 2. RESPECT EPA: EPA 1.8g/d + statin vs statin alone in stable CAD 3. ISCHEMIA-EXTENDed: interim mortality analysis of ISCHEMIA & ISCHEMIA-CKD at longer f/u 4. EMPA-KIDNEY: empagliflozin vs pbo in CKD

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Sanjay Kaul

@kaulcsmc

2 years

1/ My TOP 3 Trials at ESC 2022 in Barcelona Criterion: evidence gap & potential clinical impact 1. TIME: Nocturnal vs conventional morning dosing of BP meds 2. REVIVED_BCIS2: PCI+OMT vs OMT in ischemic CMP with LVEF <35% & viability 3. DELIVER: Dapagliflozin in HF with EF >40%

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Sanjay Kaul

@kaulcsmc

4 years

@FDASpox @MayoClinic Pray tell me how 3.5% difference in mortality (6.5% vs 10%) translates into 35 lives saved per 100 patients treated. It should be 35 lives saved per 1000 (THOUSAND) patients treated. Please ask @SteveFDA to issue a correction and stop perpetuating this error!

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Sanjay Kaul

@kaulcsmc

3 years

1/ Congratulations to the EMPEROR-Preserved Trial Investigators and participants on this landmark trial. Here are my top 10 observations: 1. Excellent trial conduct with vital status missing in only 0.6%

Empagliflozin in Heart Failure with a Preserved Ejection Fraction | NEJM

Sodium–glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with hea...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 months

Another null trial in patients post-MI! We have 3 heart failure trials (EMPEROR-Preserved, EMPEROR-Reduced, EMPULSE), 1 CKD trial (EMPA-Kidney), & 1 post-MI trial (EMPACT-MI) which show no mortality benefit with empagliflozin.

Empagliflozin after Acute Myocardial Infarction | NEJM

Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safet...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 months

1/ DanGer Shock Trial “Impella might finally get to brag about a positive trial”!

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock | NEJM

The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic sh...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 years

1/ Kudos to EMPA-KIDNEY Investigators & participants. Here are my key observations: 1. Excellent trial conduct with <1% missing data 2. Statistically persuasive benefit on PEP (28% RRR) with 14% RRR in all-cause hospitalization.

Empagliflozin in Patients with Chronic Kidney Disease | NEJM

The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of tre...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 years

@VPrasadMDMPH I am not sure evidence-based medicine ever mattered, but what is clear is that remuneration-based medicine always has.

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Sanjay Kaul

@kaulcsmc

2 months

1/ REDUCE-AMI Trial Beta blocker post-MI and LVEF >50% Open-label registry-based RCT, N=5020 Power 80%, delta HR 0.75, expected 3% annual rate in control Median f/u: 3.5y

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction | NEJM

Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

1 year

1/ TRILUMINATE Pivotal Trial Tricuspid repair with TriClip™ device vs medical therapy in symptomatic pts with severe tricuspid regurgitation Planned N=750 Reported N=350 at 1y f/u (why not wait to complete enrollment?)

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Sanjay Kaul

@kaulcsmc

2 months

1/ PREVENT “If it is too good to be true, then it probably is” PCI+OMT vs OMT in non-flow limiting high-risk vulnerable plaques. N= 1606 PEP: cardiac death, TV-MI, ID-TVR, hosp. for UA/prog. angina at 2y 80% power, delta 30% RRR from 12% control

Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatm...

In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared...

www.thelancet.com

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Sanjay Kaul

@kaulcsmc

7 months

My top 3 LBCTs at AHA DAPA-MI: A Registry-Based RCT of Dapagliflozin in Patient with AMI Without DM SELECT: Semaglutide & Cardiovascular Outcomes in Patients with Overweight or Obesity Who Do Not Have DM ORBITA-2: PCI for Stable Angina: A Randomized, Placebo-Controlled Trial

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Sanjay Kaul

@kaulcsmc

3 years

@JReinerMD @drjohnm In communicating risk, perspective is important •Risk of dying from aspirin =10 out of 100,000 •Risk of dying in a car accident =155 out of 100,000 •Risk of a nonfatal allergic reaction with COVID vaccine =0.35 out of 100,000 Should aspirin & cars be taken off the market?

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Sanjay Kaul

@kaulcsmc

7 months

DAPA-MI A case of 'divining' a positive outcome with 'misuse' of Win Ratio! PEP driven by most prevalent but arguably least relevant components. Number of ties for 7-component PEP exceeded number of wins or losses! CV death/hHF: HR 0.95, 0.64-1.40

Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure

In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. In this international registry-based, ra...

evidence.nejm.org

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Sanjay Kaul

@kaulcsmc

2 years

TRANSFORM-HF 85% power to detect 20% RRR in all-cause mortality (PEP) Expected PEP events = 721 in 6000 pts Observed = 747 in 2841 pts HR 1.02, 0.89-1.18, p=0.77 95% CI excludes 20% RRR OT = ITT analysis Pragmatic trials are challenging. …

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Sanjay Kaul

@kaulcsmc

2 years

REVIVED-BCIS2 Key finding: 1/ PCI in patients with MVCAD, LVEF<35%, and viable myocardial segments + OMT did not reduce risk of ACM or hHF, improve LVEF or QoL outcomes c/w OMT. Unplanned revascularization favored PCI/OMT & major bleeding favored OMT, especially at 1y.

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Sanjay Kaul

@kaulcsmc

2 years

Kudos to DELIVER Investigators & participants. Here are my top 10 observations: 1. Excellent trial conduct with PEP & vital status missing in only 52 & 4 patients, respectively 2. Statistically persuasive benefit on PEP (18% RRR) with 21% RRR in worsening HF & 12% RRR in CV death

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Sanjay Kaul

@kaulcsmc

2 years

PROMINENT (Pemafibrate varies Plbo) TG lowering did not translate into benefit, thereby questioning whether TG is truly a risk factor for ASCVD, and therefore a target for therapeutic intervention.

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Sanjay Kaul

@kaulcsmc

2 years

@venkmurthy Given the null results in POST-PCI, ISCHEMIA, COURAGE, etc. what is the role of stress testing (SPECT or PET-MPI) in patients with SIHD (known obstructive CAD)?

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Sanjay Kaul

@kaulcsmc

7 months

Few observations on ORBITA-2 Kudos to investigators for well-designed & executed trial that isolates an antinaginal effect of PCI over & above placebo PEP: 2.9 vs 5.6 (modest effect) Anginal episodes: 0.3 vs 0.7/d Anginal meds: 0.2 vs 0.3/d

A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina | NEJM

Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

7 months

ARTESIA, apixaban vs aspirin in subclinical atrial fibrillation (SCAF) N= 4102, age 77y, 36% women, CHADSVAC 3.9, mean f/y 3.5y 80% power for 35% RRR event-driven, prespecified evens: 248, observed 141 Expected control event rate 2.75%/PY, observed 1.24%

Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation | NEJM

Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillat...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

7 months

SELECT PEP: 569/8803 (6.5%) vs 701/8803 (8.0%), HR 0.80, 0.72-0.90, p<0.001 CV death: 2.5% vs 3%, 0.85, 0.71-1.01, p=0.07 HF composite: 3.4 vs 4.1%, 0.82, 0.71-0.96 ACM: 4.3% vs 5.2%, 0.81, 0.71-0.93 hHF: 1.0% vs 1.4%, 0.79, 0.60-1.03 Renal composite: 1.8 vs 2.2, 0.78, 0.63-0.96

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Sanjay Kaul

@kaulcsmc

2 years

Key finding: “The recommended troponin thresholds in these consensus statements (>10, ≥35, and ≥70 times the upper reference limit) were exceeded in 97.5%, 89.4%, and 74.7% of patients, respectively, within the first day after surgery.”

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality | NEJM

Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial ...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 years

@michaelTCTMD @drjohnm , @mmamas1973 , @venkmurthy Personal sentimentality trumps societal responsibility! Why bother doing the trials if one is so easily persuaded by their own preconceived notions to ignore the trial results? Evidence-be-damned medicine?

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Sanjay Kaul

@kaulcsmc

4 years

@SteveFDA Where is your apology to the 18000 FDA employees for not having their back when POTUS disparaged their integrity and credibility right in front of you?

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Sanjay Kaul

@kaulcsmc

4 years

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Sanjay Kaul

@kaulcsmc

2 years

If a treatment intervention reduces cause-specific mortality but has no impact on all-cause mortality, what does it mean? What is the optimal mortality outcome to evaluate in myocardial revascularization (PCI vs CABG; OMT vs PCI/CABG) trials?

Mortality in Randomized Clinical Trials Comparing PCI With CABG

This meta-analysis evaluates the difference in all-cause and cause-specific mortality in randomized clinical trials comparing percutaneous coronary intervention with coronary artery bypass grafting...

jamanetwork.com

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Sanjay Kaul

@kaulcsmc

2 years

DCP: Chlorthalidone (CTD) vs HCTZ in over 13K VA pts CTD touted to have better 24hr BP control & pleiotropic effects. PEP=MACE Powered for RRR 17.5% HR 1.04, 0.94-1.16 95% CI excludes 17.5% RRR Negative or inconclusive? Subgroups are tricky to interpret RCTs key to dispel myths!

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Sanjay Kaul

@kaulcsmc

8 months

After CREDENCE, DAPA-CKD, & EMPA-KIDNEY, FLOW is 4th RCT in CKD to be stopped early. All 4 RCTs are event-driven; 3 were stopped at 50-60% accrual of planned events. How many of planned 854 events accrued in FLOW? Last time a HF RCT was stopped early?

News Details

www.novonordisk.com

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Sanjay Kaul

@kaulcsmc

3 years

Another one bites the dust! Improved PCI with FFR guidance & current generation DES did not prove to be noninferior to CABG in multivessel disease. In fact it was inferior to CABG with respect to MACCE and up to 110% worse with respect to MACE.

Fractional Flow Reserve–Guided PCI as Compared with Coronary Bypass Surgery | NEJM

Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studie...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

3 years

1/ Despite intuitively appealing, why we must resist the temptation to compare EMPEROR-Preserved vs PARAGON-HF. EMPEROR-P is a placebo-controlled trial while PARAGON is an active control trial.

Empagliflozin and Major Renal Outcomes in Heart Failure | NEJM

In a planned pooled analysis of two trials that evaluated empagliflozin in patients with heart failure, major adverse renal outcomes occurred in 2.8% of the patients who received empagliflozin and ...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 years

Do you agree with conclusion of PROTECTED-TAVR "...the results may not rule out a benefit of CEP during TAVR'? Study was designed to detect a 2% ARD (presumably a clinically important difference), and '95% CI rule out this effect' would have been a more appropriate conclusion.

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Sanjay Kaul

@kaulcsmc

1 year

How strong is the evidence for dietary sodium restriction in heart failure (or in hypertension)? @hswapnil @spjuraschek

Dietary Sodium Restriction in Patients with Heart Failure | NEJM

This feature about a patient with heart failure offers a case vignette accompanied by two essays, one supporting recommendation of a low-sodium diet and the other recommending no sodium ...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

1 year

1/ A recent publication in EHJ has resurrected the debate on casual inference based on observational studies. Death in SWEDEHEART Registry: 340 PCI vs 1794 CABG IR: 68 vs 36/1000 PY Crude RR: 1.90, 1.70-2.12 IPW HR: 2.0, 1.5-2.7 IV HR: 1.5, 1.1-2.0

PCI or CABG for left main coronary artery disease: the SWEDEHEART registry

AbstractAims. An observational nationwide all-comers prospective register study to analyse outcomes after coronary artery bypass grafting (CABG) or percuta

academic.oup.com

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Sanjay Kaul

@kaulcsmc

1 year

1/ @drjohnm has raised Qs regarding interpretation of CABANA Time to revisit the trial Caveat: ITT is the only VALID analysis in an open-label RCT Favorable ‘As Treated’ or ‘Per Protocol’ analyses are subject to potential bias in favor of ablation.

Effect of Catheter Ablation vs Antiarrhythmic Drugs on Mortality, Stroke, Bleeding, and Cardiac...

This randomized trial compares the effect of pulmonary vein isolation via catheter ablation vs rate and rhythm control using medical therapy on a composite outcome of death, disabling stroke, serious...

jamanetwork.com

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Sanjay Kaul

@kaulcsmc

2 years

3/ REVIVED clarifies evidentiary landscape for PCI Unequivocal evidence of benefit for PCI is confined to primary PCI. Evidence for NSTEMI is conditional, dependent on timing of PCI, risk of patient, & choice of endpoint. No Evidence for SIHD +/- LV systolic dysfunction.

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Sanjay Kaul

@kaulcsmc

3 years

Evidence hierarchy in HF: All-cause death/CV death HHF HF event Functional outcomes: QoL, 6MWT, NYHA Biomarkers: NT-proBNP, Troponin Is there an MCID for NT-proBNP? For which outcome? Trying to understand Rx benefit in PARALLAX. Are the results favorable or neutral for ARNI?

JAMA

@JAMA_current

3 years

Study found treatment w sacubitril/valsartan vs standard treatment w enalapril, valsartan, or placebo resulted in a statistically significant reduction in plasma NT-proBNP levels at 12 wk but no significant change in the 6-minute walking distance at 24 wk

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Sanjay Kaul

@kaulcsmc

1 year

Total HHF or CV death PARAGON-HF (N=4822): 849 vs 1009, RR 0.87, 0.75-1.01, p=0.06 PARAGON-HF + PARAGLIDE-HF (N=5262): 975 vs 1108, RR 0.87, 0.76-0.99, p=0.04 How much has the needle moved in support of ARNI for HFmrEF or HFpEF? @drjohnm , @djc795

Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a...

AbstractAims. The PARAGLIDE-HF trial demonstrated reductions in natriuretic peptides with sacubitril/valsartan compared with valsartan in patients with hea

academic.oup.com

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Sanjay Kaul

@kaulcsmc

2 months

@DFCapodanno If we are designing trials in a frequentist paradigm of null hypothesis significance testing, we should stick to statistical rules of engagement. First specify, what we are going to do, then do exactly what we said we are going to do. Alternatively, embrace Bayesian approaches.

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Sanjay Kaul

@kaulcsmc

2 years

1/ ISCHEMIA-EXTENDed (interim analysis) Prospective observational study with primary outcome of all-cause death, CV death & non-CV death at 10y. Mortality NOT centrally adjudicated. 3.2y f/u HR: 0.87 (0.66-1.15) CV death, 1.05 (0.83-1.32) ACM, & 1.63 (1.06-2.52) non-CV death.

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Sanjay Kaul

@kaulcsmc

4 years

Just published in JACC Is conclusion of noninferiority justified? Is choice of NACE (combined efficacy/safety) justified? HR of 2.51 not r/o for all-stroke/TIA for LAAC vs DOAC No bleeding/CV death advantage for LAAC Was trial doomed to inconclusive result because of NACE as PEP?

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Sanjay Kaul

@kaulcsmc

2 years

Mortality & SGLT2i in HF: Strictly speaking, no individual trial in HF has demonstrated a mortality benefit with SGLT2i, however, none powered for it. DAPA-HF: CV death was not prespecified in testing hierarchy which stopped at renal composite; result, therefore exploratory.

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Sanjay Kaul

@kaulcsmc

1 year

@elmir1omerovic @yudapearl @f2harrell @stephensenn “The plain fact is that 70 years ago Ronald Fisher gave scientists a mathematical machine for turning baloney into breakthroughs, and flukes into funding. It is time to pull the plug.”

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Sanjay Kaul

@kaulcsmc

1 year

1/ Prompted by the recent JAMA paper on Emulation, revisiting evidentiary landscape for ARNI in HF PARADIGM-HF (vs enalapril in HFrEF): PEP (CV death/HHF) met; CV death, ACM ⬇️; FDA approved PARAGON-HF (vs valsartan in HFpEF): PEP (CV death/total HHF) not met; FDA approved

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Sanjay Kaul

@kaulcsmc

3 years

1/ ARNI RCTs PARADIGM-HF (vs enalapril in HFrEF):PEP (CV death/HHF) was met; CV death, ACM reduced PARAGON-HF (vs valsartan in HFpEF):PEP (CV death/total HHF) not met PARADISE-MI (vs ramipril in LV dysfunction & HF post-MI):PEP (CV death/HHF) not met

Angiotensin Receptor–Neprilysin Inhibition in Acute Myocardial Infarction | NEJM

In patients with symptomatic heart failure, sacubitril–valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-conve...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

10 months

My interpretation of the evidence is aligned with this report. Rather than withdrawing from Guideline Writing, 2 surgeons from AATS & STS should have insisted on publishing a minority 'dissenting' report a la SCOTUS. Time for Task Force to reconsider!

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Sanjay Kaul

@kaulcsmc

7 months

“In patients with no plaque or calcium, having a FAI score above 75th percentile was associated with a HR of 11.6 (95% CI: 3.51-38.21) for cardiac mortality compared to patients below 25th percentile” How does one reconcile this with the “power of zero”?

Coronary Inflammation on CCTA as Predictor of Cardiac Events: the ORFAN Study

Key Points: Out of all patients who undergo a CCTA, the highest number of cardiac…

cardiologynownews.org

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Sanjay Kaul

@kaulcsmc

4 years

@cardiobrief @ProfDFrancis I have watched, to my consternation, many times my interventional colleagues get a hug from family members for saving their loved one’s life (from PCI of a side branch). But I never get a hug for prescribing Lipitor which actually saves lives! Cache of interventional cardiology?

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Sanjay Kaul

@kaulcsmc

4 years

@SherylNYT @matthewherper @CDCgov , @CDCDirector Whether CDC walks it back or not, no reasonable physician should follow this guideline. It is not fact- or evidence-based. It is eminence-based.

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Sanjay Kaul

@kaulcsmc

2 years

@drandrewsharp Slightly is the understatement of the day! You design a study for an unrealistic 50% reduction in stroke at 72h, you fail to win on PEP, and then you still declare victory based on a potentially 'spurious' result (cannot r/o a type 1 error), and proclaim wide use of the device!🧐

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Sanjay Kaul

@kaulcsmc

1 year

Although testosterone replacement was noninferior to placebo with respect to MACE & MACE+, it was associated with increase in: Cor. Revasc. 0.9% Nonfatal arrhythmia 1.9% A fib 0.9% VTE 0.5% AKI 0.8% Does benefit of TRT exceed risk?

Cardiovascular Safety of Testosterone-Replacement Therapy | NEJM

The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. In a multicenter, randomized, double-blind, placebo-controlled,...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

2 months

RELIEVE-HF Randomized double-blind, placebo-controlled trial of Interatrial shunting using V-Valve in 508 pts with HFrEF (EF<40%) & HFpEF (EF>40%) Null effectiveness result in overall cohort No safety concerns Favorable benefit-risk in HFrEF cohort, driven by clinical outcomes

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Sanjay Kaul

@kaulcsmc

2 years

@pash22 @LVignaResearch @pomyers @Argenscore @VictorDayan1 @ovidiogarciav @dr_benoy_n_shah @mmamas1973 @MadalinaGarbi @susan_bewley @TomPMarshall If up to 50% of guideline recommendations are based on 'expert opinion' or 'consensus' (LOE C), do they belong in guidelines?

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Sanjay Kaul

@kaulcsmc

3 months

Interesting letters on ORBITA 2 published in NEJM today. How best to communicate placebo-resistant treatment effect of PCI to patients? Two fewer anginal episodes/day or 1 fewer med/day or 1 extra minute on treadmill (? baseline treadmill time)

A Placebo-Controlled Trial of PCI for Stable Angina | NEJM

To the Editor: In the editorial accompanying the article by Rajkumar and colleagues (Dec. 21 issue)1 on the results of the ORBITA-2 trial involving the use of percutaneous coronary intervention (PC...

www.nejm.org

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Sanjay Kaul

@kaulcsmc

4 years

@StevenSalzberg1 @matthewherper @VincentRK , @skathire Thank you @StevenSalzberg1 for raising the issue, listening to reasoned and constructive feedback, and changing course. Scientific discourse at its very best!

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Sanjay Kaul

@kaulcsmc

7 months

@drjohnm Increased stroke risk also seen in AZALEA-TIMI 71, which was stopped early. Guess there is no free lunch when it comes to improving bleeding risk without compromising stroke/thrombotic risk.

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Sanjay Kaul

@kaulcsmc

2 years

Effect of unmeasured confounders ASCERT registry (CABG vs PCI) If frailty was present in 10% of CABG gp (green line) but in 35% of PCI gp (x axis), & if frailty increased death risk by HR ~2, then frailty alone could account for observed diff. in mortality

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Sanjay Kaul

@kaulcsmc

1 year

1/ CLEAR OUTCOMES Bempedoic acid vs placebo in statin-intolerant patients 22084 screened, 13970 enrolled (63%) 4-wk single-blind pbo run-in period >95% power to detect 17% RRR (delta) f/u 3.4y Missing data: 5% PEP, 0.5% vital status 30% pr. prevention cohort LDL 139, CRP 2.3

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Sanjay Kaul

@kaulcsmc

2 years

@SVRaoMD @FaisalBakaeen I was there & I did not hear Faisal ‘destroying’ any trial. He questioned whether ISCHEMIA provided justification to downgrade CABG recommendation (if that is what really happened!) for normal or mildly reduced LVEF. Not unreasonable IMO.

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Sanjay Kaul

@kaulcsmc

2 years

What makes it worse is a NNT is estimated for a secondary outcome (disabling outcome) leading to the tall claim that "CEP should be considered in all patients undergoing TAVR". Embellishment to the extreme!

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Sanjay Kaul

@kaulcsmc

2 years

@drjohnm The graveyard of reperfusion injury is littered with many therapies that have failed. Now comes TXL, & we have a whopping (‘too good to be true’) treatment effect. Given the prior, don’t you think we need to replicate these findings before applying it into clinical practice?

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Sanjay Kaul

@kaulcsmc

6 months

1/ Does the evidence support Class IA guideline recommendation for catheter ablation for AF HFrEF? 2019 guidelines: Class IIb, LOE B (to potentially lower mortality and reduce HHF) Any new data to justify upgrading to Class IA?

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Sanjay Kaul

@kaulcsmc

8 months

Win Ratio (not significantly different) is based on 41% wins or losses. 59% ties are essentially ignored in the estimation of WR. In this scenario where ties exceed wins (or losses), can WR be informative? @ADAlthousePhD

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Sanjay Kaul

@kaulcsmc

7 months

Nonrandomized comparison of PCI or CABG c/w conservative strategy to 'better inform interpretation of ISCHEMIA' Using a 'disordered' (nonrandomized) dataset to inform interpretation of an 'ordered' (randomized) dataset! What am I missing?🤷‍♂️

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Sanjay Kaul

@kaulcsmc

3 years

@CMichaelGibson Cause & effect should not be established on the basis of case reports. Assuming background VTE rate of 0.1% in the population (1 in 1000), alpha of 0.025, power of 0.9, it would take about 42K pts to rule out a doubling of risk and about 168K pts to rule out 50% increase in risk.

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Sanjay Kaul

@kaulcsmc

5 months

I usually don’t respond to snark, but it is worthwhile reviewing the approval history of these devices.

vjyden sam

@rational_doc

5 months

@kaulcsmc @drjohnm @VPrasadMDMPH @AndrewFoy82 If it were up to you guys we won’t have any progress in medicine…

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Sanjay Kaul

@kaulcsmc

2 years

@BartoszHudzik @drjohnm @mmamas1973 @mirvatalasnag @DocSavageTJU @CMichaelGibson @djc795 @DLBHATTMD @AnkurKalraMD @DFCapodanno Reminds me of what Peter McCulloch observed: “The vehemence with which evidence is proclaimed is inversely related to the strength of the evidence and directly related to the square of the prominence of the proclaimer” In other words, weaker the evidence, louder the hype!

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Sanjay Kaul

@kaulcsmc

11 months

Silencing angiotensinogen in HTN might be an effective treatment strategy. Insights from a Phase 1 Study.

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Sanjay Kaul

@kaulcsmc

3 years

How many drugs have been valued at $5B based on 81 events (8 deaths) in a 1550-pt trial that was truncated after first interim analysis among 762 patients? What are the odds that the effect size is overestimated? And the effect size will be replicated?

What we know — and don’t know — about Merck’s new Covid-19 pill

STAT looks at the unanswered questions about Merck's new Covid-19 drug, molnupiravir, and about other Covid-fighting pills in development.

www.statnews.com

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Sanjay Kaul

@kaulcsmc

3 years

With the null results from FUTURE, FLOWER-MI, and RIPCORD 2 trials, will the FAME 3 results ‘make or break’ it for FFR in complex CAD? Or will the FFR gravy train continue to chug along? Evidence be damned!

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Sanjay Kaul

@kaulcsmc

2 months

1/ This was my most eagerly anticipated trial at ACC 2024. TACT 2: PEP for 5-MACE: HR 0.93, 0.76-1.16, p=0.53 TACT DM: PEP for 5-MACE: HR 0.59, 0.44-0.79, p<0.001 TACT 2 trial failed to validate hypothesis generated from prespecified subgroup analysis of TACT

TCTMD

@TCTMD

2 months

EDTA Chelation No Help in Cutting CV Outcomes After MI in Diabetic Patients: TACT2

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Sanjay Kaul

@kaulcsmc

2 years

@Doc_Tiger @HanCardiomd @mmamas1973 @CircAHA @ALEX_MISCHIE @AnkurKalraMD @ErinMichos @DrMarthaGulati @DavidLBrownMD @djc795 @GreggWStone @PCRonline With the null results in FUTURE, FLOWER-MI, FAME-3, and RIPCORD-2, the role of FFR in decision-making process rests on a shaky foundation. If the guidelines persist with endorsing FFR, then I am left with only one conclusion: evidence-be-damned!

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Sanjay Kaul

@kaulcsmc

2 years

@rational_doc @djc795 @mmamas1973 @drrashid05 @hwijeysundera @ncurzen @DrAsifQasim @rwyeh @SVRaoMD @GreggWStone @ShelleyWood2 @DavidLBrownMD @alaide_chief @ShrillaB @mirvatalasnag @cardiojaydoc02 @rallamee @ajaykirtane @amibanerjee1 @dr_mosama @Hragy @aymanka @aayshacader @agtruesdell @KardiologieHH @iamritu Financial incentives are one among the myriad reasons shown 👇 So, no material impact on PCI volume post-COURAGE, ORBITA (I would add ISCHEMIA even though it is too early to tell) is exactly as anticipated.

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Sanjay Kaul

@kaulcsmc

22 days

Couldn't agree more! Finkelstein–Schoenfeld test is much more 'palatable' as a statistical approach; however, difficult to communicate its clinical meaningfulness. WR should only be used as a complimentary analysis to communicate FS test results.

Win Ratio: A Seductive But Potentially Misleading Method for Evaluating Evidence from Clinical...

www.ahajournals.org

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Sanjay Kaul

@kaulcsmc

2 years

@cardiobrief @JohnArnoldFndtn Larry is correct! Of 14 large RCTs conducted between 1988 & 2018, only 1 met primary endpoint (ASCEND) at cost of increased bleeding. Thus, no trial showed a positive benefit-risk balance for ASA in primary prevention (PP). FDA, CDC, NHLBI, never approved/recommended ASA for PP.

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Sanjay Kaul

@kaulcsmc

7 months

Residual angina: 61% in ORBITA vs 59% ORBITA-2 despite near-resolution of ischemia. Poor correlation of symptoms with ischemia (not new) Clinical impact? Should we offer PCI as 1st line intervention for angina relief? Offering GDMT first attenuates incremental benefit from PCI

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Sanjay Kaul

@kaulcsmc

2 years

PCI trends PCI for stable angina in US (2014) 13% PCI for stable angina in UK (2019) 34.5% ? upcoding to acute PCI in US? PCIs in asymptomatic pts: 20-25% (ACC-NCDR) vs 10% (UK) No stress test prior to PCI: 65% in UK vs 30-50% in US

Rates of Elective Percutaneous Coronary Intervention in England and Wales: Impact of COURAGE and...

www.ahajournals.org

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Sanjay Kaul

@kaulcsmc

6 months

@drjohnm @rallamee @ProfDFrancis @DavidLBrownMD @VPrasadMDMPH Why do you think ORBITA-2 should change guidelines? Establishing placebo-resistant antianginal effect of PCI (modest imo) is already ‘baked in’ the guidelines. Whether it will change current clinical practice is unclear as the latter is seldom based on evidence!

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Sanjay Kaul

@kaulcsmc

3 years

Recent trends in HF trials Recurrent events 1. Does it improve power, precision or chances of a win? 2. Any example where a trial was rescued by recurrent event outcome? Worsening HF as an endpoint (HHF + urgent HF visit) 1. Does it add much? 2. Is it an approvable endpoint?

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Sanjay Kaul

@kaulcsmc

1 year

I see the spirit of Martin Luther King and Malcolm X alive and well! So proud of these two gentlemen. I stand in solidarity with them and honor them.

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Sanjay Kaul

@kaulcsmc

4 years

And then there were two!

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Sanjay Kaul

@kaulcsmc

3 months

1/ Will empagliflozin deliver where dapagliflozin and ARNI failed? Awaiting results of EMPACT-MI at ACC 2024 Placebo-controlled RCT of empagliflozin post MI in pts with CHF or LVEF <45% Event-driven, time-to-first event trial: 532 PEP events (CV death or total hHF)

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Sanjay Kaul

@kaulcsmc

1 year

@drjohnm Eliminate recs based on expert/consensus opinion. Avoid nonrandomized studies and meta-analysis (essentially observational studies) Incorporate a formal benefit-risk and benefit-risk-cost assessment (as in HTA) PIs of guideline-relevant trials to only serve as advisors/reviewers

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Sanjay Kaul

@kaulcsmc

11 months

MIND (Mediterranean + DASH) diet did not help with dementia. Neither does intensive SBP lowering.

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Sanjay Kaul

@kaulcsmc

2 years

@rahatheart1 @pash22 @nz_philip @SABOURETCardio @DavidLBrownMD @DrMarthaGulati @MichaelJBlaha @AnnMarieNavar @rblument1 @DrHeatherJohn @ErinMichos @a_l_bailey @PamTaubMD @FaRodriguezMD @cardio10s @ASPCardio @SethJBaumMD @CiccaroneCenter @ShelleyWood2 @venkmurthy @pomyers @dompagano @VictorDayan1 The word skeptic comes from the Greek skepticos, which means “that who reflects, who questions, inspects”. So a skeptic is not some boring person who does not believe in anything, but rather someone wishing to get close to a consistent truth. A seeker of truth!

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Sanjay Kaul

@kaulcsmc

2 years

@drjohnm @narrowQRS @rdschaller @wpentz @cardiojaydoc02 @djc795 @mmamas1973 @drrashid05 @hwijeysundera @ncurzen @DrAsifQasim @rwyeh @SVRaoMD @GreggWStone @ShelleyWood2 @DavidLBrownMD @alaide_chief @ShrillaB @mirvatalasnag @rallamee @ajaykirtane @amibanerjee1 @dr_mosama @Hragy @aymanka @aayshacader @agtruesdell @KardiologieHH @iamritu @VPrasadMDMPH @AndrewFoy82 As I have said before, evidence-based medicine works best when if informs (not replace) our clinical judgment, and when it incorporates patient's preference and values. Remember, it is evidence-BASED, not evidence-BOUND!

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Sanjay Kaul

@kaulcsmc

1 year

1/ Ferric carboxymaltose (Injectafer) approved for iron deficiency in adult patients with HF & NYHA class II/III to improve exercise capacity based on CONFIRM-HF where PEP of change in 6MWT at 24 wks was met: 25m, 7m-43 m, p=0.007.

Sanjay Kaul

@kaulcsmc

1 year

FDA guidance states that improvement in functional outcomes & QoL can form the basis for approval in HF even without mortality/morbidity benefit. What magnitude of effect on 6MWT and KCCQ-TS would support approval of new Rx in DB-PC trial in HF?

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Sanjay Kaul

@kaulcsmc

2 years

1/ CTS-AMI trial Tongxinluo (TXL), traditional Chinese compound, vs placebo in STEMI TXL has protective effects on myocardial no-reflow & ischemia-reperfusion injury via PKA/eNOS pathway Design: 80% power for 30% RRR in 30-day MACCE, pbo rate 9%

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Sanjay Kaul

@kaulcsmc

2 months

@RichardAFerraro @BakhshiHooman @baileyannRN @SABOURETCardio @gbiondizoccai Implausibly large effect sizes with sparse events are seldom replicable.

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Sanjay Kaul

@kaulcsmc

1 year

Only reliable conclusion one can draw from this report is limited external generalizability of SPRINT. Lack of 'legacy effect' of BP lowering (reported previously) might also be supported. Calls for lowering BP targets based on this is a slippery slope.

Longer-Term All-Cause and Cardiovascular Mortality With Intensive Blood Pressure Control

This secondary analysis of the Systolic Blood Pressure Intervention Trial evaluates the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause...

jamanetwork.com

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Sanjay Kaul

@kaulcsmc

3 months

@sameerbansilal @PamTaubMD @CMichaelGibson Less of an issue! Using 10h as cutoff instead of 8h, CV mortality is 113/1906 vs 423/11831 (ref.), RR 1.66, 1.36-2.03. Key issue is this is based on dietary recall (highly flawed) & association is not strong enough to be immune to residual confounding, & it is counter to RCT data

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Sanjay Kaul

@kaulcsmc

4 years

@dr_benoy_n_shah Stress test in ISCHEMIA was used as a gatekeeper test for enrichment while CCTA was used as a 2nd test to filter out nonobstructive & LM CAD. Trial was not designed to compare ischemia vs CCTA. So, to infer CCTA as test of 1st choice is a case of enthusiasm exceeding evidence.

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Sanjay Kaul

@kaulcsmc

3 years

Interesting mortality results in EMPEROR-Preserved Total mortality: 422 vs 427 CV mortality: 219 vs 244, ARD 0.4%, HR 0.91, 0.76-1.09 Non-CV mortality: 203 vs 183, ARD -0.7%, RR 1.11, 0.91-1.34

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Sanjay Kaul

@kaulcsmc

4 years

Interesting peek behind the curtain! Even without this controversy, there is no credible evidence to support guideline recommendation that PCI & CABG are “comparable” for low-intermediate complexity LMD. How guideline committee endorsed this is beyond me!

The 'Grubby' Affair of the EXCEL Trial and the European Guidelines

A major trial comparing stents and surgery influenced European guidelines, but allegations of misconduct and hidden data have led many cardiologists and researchers to demand an independent analysis.

www.medscape.com

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Sanjay Kaul

@kaulcsmc

7 months

MINT (Restrictive vs liberal transfusion in MI) PEP (death or MI): Adjusted RR 1.15, 0.99-1.34, p=0.07 No significant difference! Is that not an uncharitable inference? Effect ranged from 1% benefit to 34% harm. Prob of RR >1.10 = 72%!; RR >1 = 97%

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Sanjay Kaul

@kaulcsmc

4 years

@matthewherper @SteveFDA , @US_FDA FDA might be under pressure, but clinicians should not acquiesce unless it is under the setting of a randomized controlled trial. Unfortunately, promoting political shenanigans, not innovation or protecting public health appears to be the new FDA mission.

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Sanjay Kaul

@kaulcsmc

2 years

4/ Bottom line, EMPA-KIDNEY extends nephroprotective benefit of SGLT2i to a broader spectrum of CKD, but suggests that albuminuria might be a prerequisite for benefit. 48% had UACR <300, and 20% had UACR <30.

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Sanjay Kaul

@kaulcsmc

3 years

3/ however absolute benefit in <50% EF nearly 2-fold greater than in >50% (EF < or > 50% was a stratifying variable) 5. Lack of mortality benefit not surprising. Total N=463 CV deaths, so not a power issue! 6. Null effect on renal composite, all-cause hosp., & all-cause mortality

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Sanjay Kaul

@kaulcsmc

1 year

Which amongst the following is most vulnerable to misinterpretation or misleading information?

Metaanalysis of RCTs

61

Subgroup analysis of RCTs

198

Observational studies

264

Simulation studies

118

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Sanjay Kaul

@kaulcsmc

2 years

@gcfmd @mvaduganathan @JavedButler1 What is a true HFpEF? Why the obsession with first dichotomizing, then trichotomizing, and now 'quadratomizing' HF?

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