Selection of essential medicines for the prevention and treatment of cardiovascular diseases in low and middle income countries

Abstract

Background: The incidence and mortality of cardiovascular diseases (CVDs) in low and middle income countries (LMICs) have been increasing, while access to CVDs medicines is suboptimal. We assessed selection of essential medicines for the prevention and treatment of CVDs on national essential medicines lists (NEMLs) of LMICs and potential determinants for selection.

Methods: Only operational NEMLs were considered eligible for this study. A selection of medicines listed under "cardiovascular medicines" or "blood products and plasma substitutes" in the NEMLs were included if they were present on international guidelines for the prevention and treatment of CVDs (hyperlipidemia, hypertension, platelet inhibition, ischemic stroke, stable ischemic heart disease, acute coronary syndromes, heart failure, atrial fibrillation, peripheral arterial disease and acute limb ischemia). The number and diversity of essential medicines selected for CVDs were studied. Moreover, determinants of selection of essential medicines for CVDs at a national level were explored. Data analysis was done using univariate linear regression and non-parametric tests.

Results: All medicine groups listed by the international guidelines were selected by the majority of the 34 countries studied with the exception of adenosine diphosphate receptor inhibitors which appeared on less than half of the NEMLs studied (41% of countries). The total number of essential medicines for the prevention and treatment of cardiovascular diseases (median 24 (range 16-50)) differed significantly across income levels (median range: 19.5-25, p = 0.014) and across regions (median range: 20-32, p = 0.049). When recommendations of the international guidelines were considered, over 75% of the NEMLs contained essential medicines for the majority of CVDs.

Conclusion: The main medicine classes for the management of CVDs were represented on NEMLs. Consequently, for the majority of CVDs, evidence-based guideline-recommended treatment is possible as far as selection of essential medicines is concerned. Selection will therefore not be the limiting step in access to medicines for cardiovascular diseases.

Keywords: Access to medicines; Cardiovascular diseases; Essential medicines lists; Low and middle income countries.

Fig. 1

Percentage of 34 countries with essential medicines for primary and secondary prevention of cardiovascular diseases. RAAS inhibitors: renin angiotensin aldosterone system inhibitors, from which angiotensin-converting enzyme (ACE inhibitors) and angiotensin receptor blockers (ARBs) are included. Selective beta-blocker here refers to β1-selective agents, including: metoprolol, bisoprolol, acebutolol, atenolol, betaxolol, celiprolol, esmolol, nebivolol. ADP- receptor blockers: adenosine diphosphate receptor inhibitors (especially P2Y12 receptor inhibitors) include medicines such as clopidogrel, prasugrel, ticagrelor

Fig. 2

a- Percentage of 34 countries with essential medicines selected for treatment of acute cardiovascular events (ischemic stroke, stable ischemic heart disease, acute coronary syndrome). Thrombolytic agents includes streptokinase and urokinase as well as recombinant tissue plasminogen activators (rt-PAs) such as alteplase, reteplase, and tenecteplase. Platelet inhibitors include either acetylsalicylic acid or ADP-receptor blockers (e.g. clopidogrel). Selective beta-blocker here refers to β1-selective agents, including: metoprolol, bisoprolol, acebutolol, atenolol, betaxolol, celiprolol, esmolol, nebivolol. Heparin-like medicines includes unfractionated heparin (UFH) as well as low molecular weight heparins (LMWH) e.g. enoxaparin. Ischemic stroke includes both transient ischemic attacks (TIA) and cerebrovascular accidents (CVA). Acute coronary syndrome (ACS) refers to unstable angina pectoris (AP), ST segment elevation myocardial infarction (STEMI) and non-STEMI. Treatment of complications of ACS also requires atropine, which was out of the scope of this study. b - Percentage of 34 countries with essential medicines selected for treatment of acute cardiovascular events (heart failure, peripheral arterial disease, acute limb ischemia). RAAS inhibitors: Renin-angiotensin-aldosterone system inhibitors, from which angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are included in the table. Selective beta-blocker here refers to β1-selective agents, including: metoprolol, bisoprolol, acebutolol, atenolol, betaxolol, celiprolol, esmolol, nebivolol. Dopamine* includes dopamine, dobuamine, milrinone. Medicines for pharmacological cardioversion are flecainide, dofetilide, propafenone, ibutilide, amiodarone. Medicines for maintaining sinus rhythm are amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol. Oral anticoagulants include both vitamin K antagonists (e.g. warfarin) as well as direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban). Medicines for management of claudicatio intermittens include cilostazol or naftidrofuryl. Thrombolytic agents includes streptokinase and urokinase as well as recombinant tissue plasminogen activators (rt-PAs) such as alteplase, reteplase, and tenecteplase. Platelet inhibitors include either acetylsalicylic acid or ADP-receptor blockers (e.g. clopidogrel)