Atrial fibrillation in Sub-Saharan Africa: epidemiology, unmet needs, and treatment options

Figures & data

Table 1 Selected risk factors for AF in African patients compared with the global population enrolled in a prospective registry of emergency department patients presenting with AF

	Africa	Overall
Number of patients with AF	1,137	15,400
Age, years, mean (SD)	57* (19)	66 (15)
Hypertension, %	54*	62
Previous stroke or TIA, %	14	14
Heart failure, %	64*	35
Diabetes mellitus, %	14*	22
Rheumatic heart disease, %	22*	2
CHADS2score, mean	1.8	1.8

Notes:

* Significantly different from the rest of the world (P<0.005). Data from Walker et al.³⁷

Abbreviations: AF, atrial fibrillation; CHADS₂, Congestive heart failure, Hypertension, Age ≥75 years, and Diabetes (one point each), Stroke or transient ischemic attack (two points); SD, standard deviation; TIA, transient ischemic attack.

Table 2 Phase III clinical trial results for the NOACs

Comparator	RE-LY (dabigatran 110 mg)^Citation55	RE-LY (dabigatran 150 mg)^Citation55	ROCKET AF (rivaroxaban 20 mg)^Citation86	ARISTOTLE (apixaban 5 mg)^Citation56	AVERROES (apixaban 5 mg)^Citation57	ENGAGE AF-TIMI 48 (edoxaban 60 mg)^Citation58	ENGAGE AF-TIMI 48 (edoxaban 30 mg)^Citation58
	Warfarin	Warfarin	Warfarin	Warfarin	Aspirin	Warfarin	Warfarin
Trial design	Randomized, open-label, rater-blinded, noninferiority trial	Randomized, open-label, rater-blinded, noninferiority trial	Randomized, double-dummy, double-blind, noninferiority trial	Randomized, double-dummy, double-blind, noninferiority trial	Randomized, double-dummy, double-blind, superiority trial	Randomized, double-dummy, double-blind, noninferiority trial	Randomized, double-dummy, double-blind, noninferiority trial
Stroke or systemic embolism	RR: 0.91 (95% CI: 0.74, 1.11); P=0.34*	RR: 0.65 (95% CI: 0.52, 0.81); P<0.001*,**	HR: 0.88 (95% CI: 0.75, 1.03); P=0.12a,*	HR: 0.79 (95% CI: 0.66, 0.95); P=0.01*	HR: 0.45 (95% CI: 0.32, 0.62); P<0.001**	HR: 0.79 (97.5% CI: 0.63, 0.99);b P<0.001*	HR: 1.07 (97.5% CI: 0.87, 1.31);b P=0.005*
Hemorrhagic stroke	RR: 0.31 (95% CI: 0.17, 0.56); P<0.001	RR: 0.26 (95% CI: 0.14, 0.49); P<0.001	HR: 0.59 (95% CI: 0.37, 0.93);c P=0.024	HR: 0.51 (95% CI: 0.35, 0.75); P<0.001	HR: 0.67 (95% CI: 0.24, 1.88); P=0.45	HR: 0.54 (95% CI: 0.38, 0.77); P<0.001	HR: 0.33 (95% CI: 0.22, 0.50); P<0.001
Intracranial hemorrhage	RR: 0.30 (95% CI: 0.19, 0.45); P<0.001	RR: 0.41 (95% CI: 0.28, 0.60); P<0.001	HR: 0.67 (95% CI: 0.47, 0.93);c P=0.02	HR: 0.42 (95% CI: 0.30, 0.58);c P<0.001	HR: 0.69 (95% CI: 0.38, 1.90); P=0.69	HR: 0.47 (95% CI: 0.34, 0.63);c P<0.001	HR: 0.30 (95% CI: 0.21, 0.43);c P<0.001
Myocardial infarction	RR: 1.29 (95% CI: 0.96, 1.75); P=0.09	RR: 1.27 (95% CI: 0.94, 1.71); P=0.12	HR: 0.81 (95% CI 0.63, 1.06);c P=0.121	HR: 0.88 (95% CI: 0.66, 1.17); P=0.37	HR: 0.86 (95% CI: 0.50, 1.48); P=0.59	HR: 0.94 (95% CI: 0.74, 1.19); P=0.60	HR: 1.19 (95% CI: 0.95, 1.49); P=0.13
All-cause mortality	RR: 0.91 (95% CI: 0.80, 1.03); P=0.13	RR: 0.88 (95% CI: 0.77, 1.00); P=0.051	HR: 0.92 (95% CI: 0.82, 1.03); P=0.15	HR: 0.89 (95% CI: 0.80, 0.998); P=0.047	HR: 0.79 (0.62, 1.02); P=0.07	HR: 0.92 (95% CI: 0.83, 1.01); P=0.08	HR: 0.87 (95% CI: 0.79, 0.96); P=0.006
Major bleeding	RR: 0.80 (95% CI: 0.70, 0.93); P=0.003	RR: 0.93 (95% CI: 0.81, 1.07); P=0.32	HR: 1.04 (95% CI: 0.90, 1.20);c P=0.58	HR: 0.69 (95% CI: 0.60, 0.80);c P<0.001	HR: 1.13 (95% CI: 0.74, 1.75); P=0.57	HR: 0.80 (95% CI: 0.71, 0.91);c P<0.001	HR: 0.47 (95% CI: 0.41, 0.55);c P<0.001

Notes: All values are for the intention-to-treat populations unless otherwise stated.

* Noninferior to comparator;

** superior to comparator;

a the primary end point for ROCKET-AF used the per-protocol population. In the per-protocol analysis, the HR for stroke or systemic embolism with rivaroxaban vs warfarin was 0.79 (95% CI: 0.66, 0.96; P<0.001 for noninferiority);

b modified intention-to-treat population in the treatment period;

c safety on-treatment population.

Abbreviations: CI, confidence interval; HR, hazard ratio; NOAC, non-vitamin K antagonist oral anticoagulants; RR, relative risk; RE-LY AF, Randomized Evaluation of Long-Term Anticoagulation Therapy ROCKET-AF, Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; ARISTOTLE, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; AVERROES, Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; ENGAGE AF-TIMI, Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation -Thrombolysis in Myocardial Infarction.

Table 3 Guideline recommendations on the use of antithrombotic therapy for the prevention of stroke in patients with nonvalvular atrial fibrillation, based on stroke risk

Guideline	CHADS2 risk score
	0	1	≥2
South African Stroke Society (2010)	Aspirin alone	Warfarin or aspirin, taking into account patient preferences, bleeding risk, and access to reliable INR monitoring	Warfarin recommended, taking into account patient preferences, bleeding risk, and access to reliable INR monitoring
ACCP (2012)	No antithrombotic therapy or aspirin alone	OAC suggested rather than no therapy or aspirin/aspirin + clopidogrel If OAC unsuitable or not desired, aspirin + clopidogrel suggested rather than aspirin alone	OAC suggested rather than no therapy or aspirin/aspirin + clopidogrel If OAC unsuitable or not desired, aspirin + clopidogrel suggested rather than aspirin alone
Guideline	CHA2DS2–VASc risk score
	0	1	≥2
ESC (2012)	No antithrombotic therapy	Consider OAC, depending on individual risk (not recommended in female patients aged <65 years with lone AF)	NOAC (dabigatran, rivaroxaban, and apixaban) or VKA recommended. If patient refuses OAC, consider aspirin + clopidogrel
NICE (2014)	No OAC recommended	Consider OAC for men, taking into account bleeding risk and individual patient risks and preferences	OAC recommended, taking into account bleeding risk and individual patient risks and preferences
ACC/AHA/HRS (2014)	Reasonable to omit antithrombotic therapy	Either no therapy or consider aspirin or OAC	OAC recommended, either warfarin (INR 2–3) or NOAC
ASA/AHA (2014)	Reasonable to omit antithrombotic therapy	No antithrombotic therapy, anticoagulant therapy, or aspirintherapy may be considered	OAC recommended, either warfarin (INR 2–3) or NOAC

Abbreviations: ACC/AHA/HRS, American College of Cardiology/American Heart Association/Heart Rhythm Society; ACCP, American College of Chest Physicians; AF, atrial fibrillation; ASA, American Stroke Association; CHADS₂, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes (one point each), Stroke or transient ischemic attack (two points); ESC, European Society of Cardiology; INR, international normalized ratio; NICE, National Institute for Health and Care Excellence; NOAC, non-vitamin K antagonist oral anticoagulants; OAC, oral anticoagulant; VKA, vitamin K antagonist.

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