Quality Assessment of 7 Cardiovascular Drugs in 10 Sub-Saharan Countries: The SEVEN Study

Substandard and falsified medicines pose a serious threat to patient safety and public health.¹ Studies on the quality of drugs have focused mainly on antimicrobial agents, such as antiretroviral therapy (for human immunodeficiency virus) and antimalarial medications.² Although cardiovascular disease kills millions of Africans,³ to our knowledge, little published research has explored the quality of essential cardiovascular disease medicines to date. We therefore performed a quality assessment of 7 commonly used cardiac drugs (ie, an anticoagulant drug, a statin, and 5 antihypertensive drugs) in 10 countries of sub-Saharan Africa.

We assessed 7 of the most common cardiovascular medicines used in Africa: the anticoagulant acenocoumarol, the statin simvastatin, and 5 antihypertensive drugs, including furosemide, hydrochlorothiazide (a diuretic), captopril (an angiotensin-converting enzyme inhibitor), atenolol (a β-blocker), and amlodipine (a calcium channel blocker).

According to Medicine Quality Assessment Reporting Guidelines,⁴ we prospectively collected samples using standardized methods between November 2012 and August 2014 from pharmacies and street markets in 10 African countries, including Benin, Burkina Faso, Congo-Brazzaville, Côte D’Ivoire, Guinea, Mauritania, Niger, the Democratic Republic of the Congo, Senegal, and Togo.

A falsified medicine is one which is deliberately and fraudulently mislabeled. Falsified drugs may contain different ingredients (both harmless and toxic) from the one stated on the label or a different content of the expected active ingredient. Substandard medicines are those produced by legitimate manufacturers that do not meet required quality specifications. We did not conduct forensic analyses of the drugs to determine whether they were substandard or falsified drugs.

A reversed-phase liquid chromatography with tandem mass spectrometry method was developed⁵ in a certified public laboratory in Paris, France, to accurately quantify the active ingredient. Three quality categories were defined based on the ratio of measured to expected dose of the active ingredient in the sample; a ratio of 95% to 105% indicated good quality, a ratio of 85% to less than 95% or greater than 105% to 115% indicated low quality, and a ratio less than 85% or greater than 115% indicated very low quality. Overall, drugs were considered to be of poor quality if they were low or very low quality.

According to the sampling protocol, 3468 samples were collected and 1530 were tested at random, of which 249 (16.3%) were deemed to be of poor quality. The prevalence of poor-quality drugs differed significantly between drugs (P < .001), with the lowest prevalence for acenocoumarol (0 of 165 samples [0%]) and highest for amlodipine (87 of 305 samples [28.5%]), and between countries, although this difference did not reach statistical significance (P = 0.08) (Table). The proportion of poor-quality drugs exceeded 20% in Benin, Congo-Brazzaville, Niger, and the Democratic Republic of the Congo and was below 10% in Guinea, Senegal, and Togo (Figure). While low-quality samples were observed in all 10 countries, very-low-quality samples were obtained only from Niger (1 of 100 samples [1.0%]), Côte D’Ivoire (3 of 295 samples [1.0%]), Benin (10 of 325 samples [3.1%]), and Congo-Brazzaville (10 of 150 samples [6.7%]).

To our knowledge, we have presented the first data on the quality of cardiovascular drugs in countries in sub-Saharan Africa. We found a high prevalence of poor-quality drugs, with a little less than 1 in 6 samples failing to meet standards.

The observed variation in quality by country merits consideration. Indeed, in 2013, operation BIYELA was carried out in 23 African countries and resulted in the interception of more than 500 million illicit or falsified drugs, most of which were from Benin, Tanzania, and the Democratic Republic of the Congo.⁶

A combination of political apathy and corruption may make the task of improving the quality of drugs especially challenging in the developing world. Increasing public awareness and heightening international scrutiny are necessary to bring about changes. Improving the quality of cardiovascular drugs would be a major achievement for the prevention and control of noncommunicable diseases in sub-Saharan Africa. Improvement in the public’s access to effective medications also remains an important goal that will help to achieve the target of the United Nations of a 25% reduction in premature cardiovascular disease mortality by 2025.⁷ Accessibility to quality drug testing for interested parties is a crucial requirement.

Corresponding Author: Marie Antignac, PharmD, PhD, Department of Pharmacy, Saint-Antoine Hospital, East Paris University Hospitals, AP-HP, 184 Rue du Faubourg Saint-Antoine, Paris, France 75012 (marie.antignac@aphp.fr).

Published Online: October 19, 2016. doi:10.1001/jamacardio.2016.3851

Author Contributions: Drs Antignac and Jouven had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Antignac, Diop, Jouven.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Antignac, Jouven.

Critical revision of the manuscript for important intellectual content: Antignac, Jouven.

Statistical analysis: Antignac, Jouven.

Obtained funding: Antignac, Jouven.

Administrative, technical, or material support: All authors.

Study supervision: Antignac, Diop, N’Guetta, Jouven.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: The SEVEN Study was exclusively supported by grant AAP-2014-042 from the National Agency of Drug Safety as well as by INSERM, AP-HP, and Paris Descartes University.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Diane Macquart De Terline, PharmD (Department of Pharmacy, Saint-Antoine Hospital) as well as Muriel Tafflet, MCH, and J. P. Empana, MD, PhD (INSERM U970), for their help with statistical analysis; Melisande Bernard, PharmD (Department of Laboratories, General Agency of Health Equipment and Products), for her help with chemical analysis; Méo Stéphane Ikama, MD (Cardiology Department, Cardiology Institute of Abidjan), Dadhi M. Balde, MD (Cardiology Department, National Hospital of Sanou Souro of Bobo Dioulasso), Yessoufou Tchabi, MD (Department of Cardiology, European Georges Pompidou Hospital), Abdallahi Sidi Aly, MD (INSERM U970), Jean Marie F. Damorou, MD (Cardiology Department, University Hospital of Lomé, Togo), and Jean Laurent Takombe, MD (Kinshasa General Hospital, Kinshasa, Democratic Republic of the Congo), for collecting drug samples; and Kumar Narayanan, MD (INSERM U970) as well as P. F. Plouin, PhD, and Eloi Marijon, PhD (Department of Cardiology, European Georges Pompidou Hospital), for reviewing the manuscript. The contributors were not compensated for their work.