Het Verbeteren van de Therapietrouw Meten is Weten Dr. E. M. van - - PowerPoint PPT Presentation

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Het Verbeteren van de Therapietrouw Meten is Weten Dr. E. M. van - - PowerPoint PPT Presentation

Oct 08, 2022 147 likes •326 views

Het Verbeteren van de Therapietrouw Meten is Weten Dr. E. M. van Maarseveen, PharmD, PhD Clinical pharmacist, clinical pharmacologist University Medical Center Utrecht NVIVG symposium, 7 september 2018 Conflicts of interest I have nothing to

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Het Verbeteren van de Therapietrouw

Meten is Weten

  • Dr. E. M. van Maarseveen, PharmD, PhD

Clinical pharmacist, clinical pharmacologist University Medical Center Utrecht

NVIVG symposium, 7 september 2018

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SLIDE 2

Conflicts of interest

I have nothing to declare in relation to the content of this talk

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Adherence in Hypertension

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Dealing with and monitoring of Adherence

Huffman et al., The Lancet 2017 DOI:https://doi.org/10.1016/S0140-6736(17)30553-6

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Towards Measuring is Knowing

The Mass Spectrometer

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Clinical Mass Spectrometry Core Facility @ UMC Utrecht Pharmacy Department

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Step 1: Qualification using mass spectrometry

Library spectrum Found spectrum

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First Results of “Objective” Monitoring

  • f Adherence to Antihypertensive Agents from Sympathy

No or less than half of the number of prescribed antihypertensive drugs could be detected in 13 (26%) and 17 (34%) patients, respectively.

de Jager et al., Hypertension 2017 de jager et al., BJCP 2018

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SLIDE 9
  • Sympathy trial: Intervention by Renal denervation

Impact on Blood Pressure?

In ten tio n -to -trea t-p o p u la tio n S elected p o p u la tio n w ith sta b le a d h eren ce

  • 2 5
  • 2 0
  • 1 5
  • 1 0
  • 5

5 1 0 D elta sy stolic b loo d p ressu re (m m H g)

D a y tim e s y sto lic A B P M 2 4 -h o u r s y sto lic A B P M O ffic e S B P

De Jager et al, Hypertension 2017

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Azizi et al., Adherence to Antihypertensive Treatment and the Blood Pressure–Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial, Volume: 134, Issue: 12, Pages: 847-857, DOI: (10.1161/CIRCULATIONAHA.116.022922)

Adherence to Antihypertensive Treatment and the Blood Pressure– Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial

Figure 2. Spaghetti plots of individual changes in daytime ambulatory systolic blood pressure

(SBP) between baseline and 6 months in the renal denervation group (red lines) and control group (blue lines) in patients who were fully adherent and nonadherent (partially nonadherent plus completely nonadherent)

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Therapeutic drug monitoring-guided definition of adherence profiles in resistant hypertension and identification of predictors of poor adherence*

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Figure 2 Differences in office diastolic blood pressure (DBP) and office heart rate values among fully adherent (AD), partially adherent (PAD) and totally nonadherent (NAD) patients, according to Kruskal–Wallis test. TDM, therapeutic drug monitoring

*Avataneo et al., Britisch Journal of clinical pharmacology, 2018

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Step 2: Quantitation of antihypertensive agents in serum

  • Combined screening and (semi-)quantification of

52 antihypertensive agents using LC-MS/MS in serum

  • Why serum?

– Quantitative option vs Qualitative urine screening – Direct exposure- effect relationship (PKPD)

  • Concentrations linked to blood pressure
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Quantitative Reporting

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CONCENTRATION RATIO (CR) = Measured Concentration/Population Cmin Example Quinalapril: CR= 20 (µg/L) /10 (µg/L) = 2

Samplenr 21711xxxx Nefine Neg Metoprolol 0,05 Triamtereen 0,04 Perindoprilaat 0,33

FARMACOLOGISCHE INTERPRETATIE Nefine niet teruggevonden. Triamtereen, perindoprilaat en metoprolol in zeer lage (waarschijnlijk supratherapeutische) CR waarden teruggevonden. CR’s kunnen duiden op inconsistente /niet- consequente therapietrouw of op enkelvoudige inname voor polibezoek, waarbij de concentraties in bloed van o.a. nifedipine te laag zijn om te detecteren. CR*= concentratie ratio = ratio gevonden waarde gedeeld door populatie dalspiegel.

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Qualitative versus Quantitative Results?

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  • Nr. of patients

P<0.001 P<0.01

Punt et al., abstract @ IATDMCT Congress, Brisbane, september 16-20, 2018

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But then…..the MS screening results……

PATIENT R B Z X P P Sample lijst 217113016601 217120420601 117120432601 117120443301 217120502501 217120504801 Used Medication Hydrochloorthiazide_204 5,77 15,93 Neg Lercanidipine_280 2,71 Metoprolol_103 0,42 Neg Telmisartan_276 5,15 Barnidipine_315 5,44 Irbesartan_207 114,96 Sotalol_255 1,04 Amlodipine_220 Neg Neg Chloorthiazide_213 Neg Doxazosin_247 Neg Neg 0,66 Neg Olmersartan_429 Neg Neg Neg Furosemide_204 Neg Canrenon_91 Neg Labetalol_311 Neg Nefidipine_284 Neg

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Current Clinical Applications

  • Adherence Screen for Routine Care
  • Research

– SYMPATHY (on/off meds) – CALM-START (on/off meds) – intervention – + antidiabetics + antiplatelets

https://www.umcutrecht.nl/nl/Ziekenhuis/Profes sionals/Diagnostiek-aanvragen/Farmalab

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Take Home Messages

  • Screening and quantification of cardiovascular agents

using LC-MS/MS is a valuable tool for objective drug adherence assessment,

  • which deserves further exploration in clinical

practice with the ultimate goal to improve treatment outcomes.

  • Objective assessment is only the beginning…..