Non-adherence to cardiovascular pharmacotherapy in Iraq assessed using 8-items Morisky questionnaire and analysis of dried blood spot samples

The study evaluated the non-adherence to selected cardiovascular medications, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, simvastatin and valsartan in Iraqi patients by applying a standardized Morisky questionnaire (8-MMAS) and by measuring therapeutic drug concentrations in dried blood spots (DBS) analysed by liquid chromatography high resolution mass spectrometry (LC-HRMS). Sixtynine patients on continued use of one or more of the selected drugs were evaluated. The questionnaire showed that 21.7% of participants were non-adherent whereas DBS analysis showed that 49.3% were non-adherent to their medications. No significant correlation between medication non-adherence and gender was detected, but adherence was negatively correlated with the number of medication in the regimen. The 8-items questionnaire was unable to differentiate nonadherence to multi-medications in the prescribed pharmacotherapy regimens. DBS is an alternative to conventional methods to monitor non-adherence objectively. Agreement between the two approaches was weak (Kappa =0.269, pvalue 0.05).


INTRODUCTION
Cardiovascular disease (CVD) is a broad term covering disorders of the heart and blood vessels.Examples include hypertension, angina, heart attack, stroke, and heart failure [1].CVDs accounts for the highest number of deaths worldwide [2].There is evidence that as many as 50% of prescribed CVD drugs worldwide are not taken by patients as recommended.Medication adherence can be assessed by indirect methods (e.g.questionnaire) or direct methods (concentration of drugs or metabolites in a biological fluid (such as urine or blood).However, no consensus has been reached on a gold standard for routine clinical practice [3].The 8-item Morisky Medication Adherence Scale (8-MMAS), provides a single qualitative ternary metric to assess adherence (low, medium, or high) depending on the total score.Conventional direct methods require large blood volumes (0.5 -10 mL) [1].Dried blood spot (DBS) sampling is an alternative to conventional methods [4].It is less invasive, typically involving the collection of just a few drops of blood from a finger or heel prick onto a filter paper [1].The aim of this research was to assess patients' non-adherence to treatment with atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, losartan, simvastatin and valsartan by 8-MMAS and determination of the target medications in DBS from the same patients and to compare the results obtained from the two approaches Proceedings of the APS@FIP Conference 2018 Hospital in Iraq during routine clinical visits.Following consent, patients were invited to complete an Arabic version of (8-MMAS) questionnaire and to provide a finger-prick blood spots samples on DBS cards.Drugs concentration in DBS was determined by liquid chromatography-high resolution mass spectrometry (LC-HRMS) [5].Patients were categorized as non-adherent when one or more of their prescribed cardiovascular medications were outside the range of (0.05) Cmax to Cmax.
However, adherence assessment by DBS showed that 35 patients (50.7%) were adherent to medications (21 males and 14 females) and 34 patients (49.3%) were non-adherent (20 males and 14 females).Both approaches showed no significant relationship between medication non-adherence and gender.The negative correlation between adherence and the number of medications was seen in both approaches.DBS analysis showed that adherence to medication was not uniform (Fig 1).44 participants (63.8%) showed agreement and 25 (36.2%)showed disagreement.22 patients were classified as adherent according to 8-MMAS but they were non-adherent according to their blood concentration.This difference may be due to prescribing errors, substandard medications, individual pharmacokinetic variability, or drug interactions.The other 3 patients were non-adherent by the 8-MMAS but were defined as adherent according to DBS analysis.The agreement between the two approached was weak (Kappa = 0.269, p-value ˂ 0.05).
The answers to the Morisky questions with respect to non-adherence were:

CONCLUSIONS
The Morisky 8-MMAS and the DBS sampling approach both indicated levels of non-adherence.Poor agreement between the two approaches was seen.The DBS derived data provided drug specific information about patient medication taking behaviour.The results from the DBS sampling indicated that non-adherence was not uniform towards the different medications in the sample medical regimens tested.

Fig. 1 .
Fig. 1.Comparison of non-adherence among the Iraq patient group for each of the target cardiovascular drugs by DBS analysis and 8-MMAS