Post hoc study to investigate the potential causes of poor quality of cardiovascular medicines collected in sub-Saharan countries.

OBJECTIVES: The incidence of cardiovascular diseases is increasing and there is a growing need to provide access to quality cardio drugs in Africa. In the SEVEN study, we analysed 1530 cardiovascular drug samples randomly collected from 10 African countries. By that time, of the seven drugs products analysed, only those containing amlodipine and captopril had very low assay values with active substance contents that could be less than 75% of those expected. In this article we investigate complementary aspects of the amlodipine and captopril samples so to explain the previously observed low assays for these two drugs. DESIGN: Post hoc analysis of the captopril and amlodipine drugs samples and their packages collected in the context of the SEVEN study. SETTING: 10 countries were concerned: Benin, Burkina Faso, Congo, Democratic Republic of the Congo, Guinea, Côte d'Ivoire, Mauritania, Niger, Senegal and Togo. PARTICIPANTS: Local scientists and hospital practitioners collected the drug samples in the 10 African countries. OUTCOME MEASURES: The drug amount and the relative amounts of drug impurities, as well as the main compounds of the drugs packaging, were analysed. RESULTS: Identification of the blister packaging of the samples led to separate both amlodipine and captopril drug samples in two groups. Mann Whitney's bilateral test showed a significant difference (p<0.0001) between the median value of the captopril dosage when tablets are packaged in blisters providing higher protection to humidity (n=105) as opposed to the tablets packaged in blisters providing lower humidity protection (n=130). CONCLUSION: Based on these results, particular attention should be paid to the materials and types of packaging used in order to minimise the lack of control over the exposures and drug circuits present in these different countries.

Poor adherence to medication and salt restriction as a barrier to reaching blood pressure control in patients with hypertension: Cross-sectional study from 12 sub-Saharan countries.

BACKGROUND: Sub-Saharan Africa is experiencing a rising burden of hypertension. Antihypertensive medications and diet are the cornerstone of effective hypertension control. AIMS: To assess adherence to medication and salt restriction in 12 sub-Saharan countries, and to study the relationship between adherence and blood pressure control in patients with hypertension. METHODS: We conducted a cross-sectional survey in urban clinics in twelve sub-Saharan countries. Data were collected on demographics, treatment and adequacy of blood pressure control in patients with hypertension attending the clinics. Adherence was assessed by questionnaires completed by the patients. Hypertension grades were defined according to European Society of Cardiology guidelines. Association between adherence and blood pressure control was investigated using multilevel logistic regression analysis, adjusting for age, sex and country. RESULTS: Among the 2198 patients, 77.4% had uncontrolled blood pressure, 34.0% were poorly adherent to salt restriction, 64.4% were poorly adherent to medication and 24.6% were poorly adherent to both. Poor adherence to salt restriction (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.03-1.72), medication (OR 1.56, 95% CI 1.25-1.93) or both (OR 1.91 1.39-2.66) was related to uncontrolled blood pressure. Moreover, poor adherence to both medication and salt restriction was related to a 1.52-fold (95% CI 1.04-2.22), 1.8-fold (95% CI 1.22-2.65) and 3.08-fold (95% CI 2.02-4.69) increased likelihood of hypertension grade 1, 2 and 3, respectively. CONCLUSIONS: High levels of poor adherence to salt restriction and medication were noted in this urban sub-Saharan study; both were significantly associated with uncontrolled blood pressure, representing major opportunities for intervention to improve hypertension control in sub-Saharan Africa.

Substandard drugs among five common antihypertensive generic medications: an analysis from 10 African countries.

OBJECTIVE: Hypertension results in more deaths than any other risk factor and has been on the rise in sub-Saharan Africa over the past few decades. Generic drugs have helped improve accessibility and affordability of antihypertensive therapy in developing countries. However, assessment of quality standards of these products is important. We performed a quality assessment of five commonly used antihypertensive generic drugs in 10 sub-Saharan African countries and studied the impact of price on quality. METHODS: Drug samples were prospectively collected using standardized methods between 2012 and 2014. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Quality was defined based on the percentage ratio of measured to expected dosage of active ingredient. RESULTS: A total of 1185 samples were assessed, of which 70.0% were generic (n = 830). Among the generic drugs, the percentage of poor-quality drugs was 24.3% (n = 202/830). The percentage ratio of measured to expected dosage of active ingredient ranged from 49.2 to 111.3%; the majority (81.7%) of the poor-quality samples had insufficient quantity of the active ingredient. Moreover, poor quality was not associated with purchase price of the drug. CONCLUSION: In this study from 10 sub-Saharan African countries, nearly one-quarter of the available generic antihypertensive drugs were found to be of poor quality. Concerted measures to improve the quality of antihypertensive drugs could lead to major improvements in hypertension control with attendant reduction of its deleterious consequences in low-income and middle-income countries.

Fighting fake medicines: First quality evaluation of cardiac drugs in Africa.

BACKGROUND: The growing menace of poor quality and falsified drugs constitutes a major hazard, compromising healthcare and patient outcomes. Efforts to assess drug standards worldwide have almost exclusively focused on anti-microbial drugs; with no study to date on cardiovascular drugs. Our study aims to assess quality of seven routinely used cardiovascular medications (anticoagulants, antihypertensives and statins) in ten Sub-Saharan African countries. METHODS: Drugs were prospectively collected using standardized methods between 2012 and 2014 from licensed (random pharmacies) and unlicensed (street-markets) places of sale in Africa. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Three quality categories were defined based on the ratio of the measured to the expected dosage of the active ingredient: A (good quality): 95% to 105%, B (low quality): 85 to 94.99% or 105.01 to 115%, C (very low quality): <85% or >115%. RESULTS: All expected medicines (n=3468 samples) were collected in Benin, Burkina-Faso, Congo-Brazzaville, the Democratic Republic of Congo, Guinea, Côte d'Ivoire, Mauritania, Niger, Togo and Senegal. Out of the 1530 samples randomly tested, poor quality (types B and C) was identified in 249 (16.3%) samples. The prevalence of poor quality was significantly increased in certain specific drugs (amlodipine 29% and captopril 26%), in generic versions (23%) and in drugs produced in Asia (35%). The proportion of poor quality reached 50% when drugs produced in Asia were sold in street-markets. CONCLUSION: In this first study assessing the quality of cardiovascular drugs in Africa, we found a significant proportion of poor quality drugs. This requires continued monitoring strategies.