Fixed dose combination drugs for cardiovascular disease in a prolonged humanitarian crisis in Lebanon: an implementation study

Abstract

Objectives: This pre-post implementation study evaluated the introduction of fixed dose combination (FDC) medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention into routine care in a humanitarian setting.

Setting: Two Médecins sans Frontières (MSF) primary care clinics serving Syrian refugee and host populations in north Lebanon.

Participants: Consenting patients ≥18 years with existing ASCVD requiring secondary prevention medication were eligible for study enrolment. Those with FDC contraindication(s) or planning to move were excluded. Of 521 enrolled patients, 460 (88.3%) were retained at 6 months, and 418 (80.2%) switched to FDC. Of these, 84% remained on FDC (n=351), 8.1% (n=34) discontinued and 7.9% (n=33) were lost to follow-up by month 12.

Interventions: Eligible patients, enrolled February-May 2019, were switched to Trinomia FDC (atorvastatin 20 mg, aspirin 100 mg, ramipril 2.5/5/10 mg) after 6 months' usual care. During the study, the COVID-19 pandemic, an economic crisis and clinic closures occurred.

Outcome measures: Descriptive and regression analyses compared key outcomes at 6 and 12 months: medication adherence, non-high density lipoprotein cholesterol (non-HDL-C) and systolic blood pressure (SBP) control. We performed per-protocol, intention-to-treat and secondary analyses of non-switchers.

Results: Among 385 switchers remaining at 12 months, total adherence improved 23%, from 63% (95% CI 58 to 68) at month 6, to 86% (95% CI 82 to 90) at month 12; mean non-HDL-C levels dropped 0.28 mmol/L (95% CI -0.38 to -0.18; p<0.0001), from 2.39 (95% CI 2.26 to 2.51) to 2.11 mmol/L (95% CI 2.00 to 2.22); mean SBP dropped 2.89 mm Hg (95% CI -4.49 to -1.28; p=0.0005) from 132.7 (95% CI 130.8 to 134.6) to 129.7 mm Hg (95% CI 127.9 to 131.5). Non-switchers had smaller improvements in adherence and clinical outcomes.

Conclusion: Implementing an ASCVD secondary prevention FDC improved adherence and CVD risk factors in MSF clinics in Lebanon, with potential for wider implementation by humanitarian actors and host health systems.

Keywords: Ischaemic heart disease; PREVENTIVE MEDICINE; PRIMARY CARE; PUBLIC HEALTH; THERAPEUTICS.

Figure 1

Flow chart of the study procedure.

Figure 2

Study enrolment and retention flow diagram reasons for not switching to FDC or for discontinuation: ‘contraindication/side effect’: any medical reported side effect [by MSF general practitioner (GP) or private physician outside MSF clinic] or any specific reported side effects from patients. ‘Patient preference’: any non-specific reason for discontinuation provided by the patient for example, ‘patient feels bad and wants to stop the medication’. ‘Doctor recommendation’: any recommendation by MSF GP to discontinue.’Other’: any non-MSF guided intervention (ie, private doctor advised to stop, without mentioning reason) or any reason that does not fit the above categories. FDC, fixed dose combination; MSF, Médecins sans Frontières.

Figure 3

Proportion of patients achieving full adherenceˆ, non-HDL cholesterol and systolic blood pressure control at 6 month (switching) and 12 month visits*. ˆAdherence was defined as self-reported MARS5 score of 25, regarding all of the FDC equivalent medications at 6 months (atorvastatin, rampiril/losartan, aspirin) and regarding the FDC for those patients who switched and were maintained on the FDC (n=351), or all the equivalent medications in the case of those discontinuing the FDC at 12 months (n=34). *6 month visit data include all patients switched to the FDC, and 12 month visit data include all patients switched to the FDC and retained in the study at 12 months, in an intention to treat analysis. BP, blood pressure; FDC, fixed dose combination; non HDL-C, non-high density lipoprotein cholesterol.

Figure 4

Distribution of continuous outcomes, non-HDL cholesterol and systolic blood pressure levels, at 6-month (switching) and 12-month visits*. *6-month visit data include all patients switched to the FDC and 12-month study visit include all patients switched to FDC and retained in the study at 12 months, in an intention-to-treat analysis. FDC, fixed dose combination; non-HDL, non high-density lipoprotein.