Atrial fibrillation and coronary artery disease: An integrative review focusing on therapeutic implications of this relationship

Table 1 Prominent studies over the last three decades highlighting the clinical impact of underlying coronary artery disease in patients suffering from atrial fibrillation

Ref.	Year	Type of study	Number of patients	Principal findings and comment
Petersen et al[37]	1990	Double blind RCT	516	Active angina was the only independent predictor of stroke on multivariate analysis [OR of 3.3 (95%CI: 1.3-8.9, P = 0.02)]
Ezekowitz et al[38]	1995	RCT	516	Active angina was an independent predictor of silent brain infarctions (15% vs 5% in those without angina; P = 0.02)
Van Walraven et al[39]	2003	Metanalysis of 6 RCTs	2501	Observed rate of stroke or TIAs was 3-fold higher in group with history of angina (5.6 vs 1.4 events/100 patient years; P = 0.002)
Goto et al[40]	2008	Observational cohort study	63589	MACCE events were consistently higher at 12 mo in AF patients with concomitant CAD compared to those without CAD (19.70 vs 14.52; P < 0.05)
Olesen et al[41]	2012	Registry based cohort study	87202	Stroke risk significantly higher in AF patients who had underlying CAD or past history of MI [HR of 1.14 (1.03-1.27)]
Rasmussen et al[42]	2011	Observational cohort study	3315	Risk of stroke or death significantly higher among those with underlying CAD [HR of 1.99 (1.46-2.72)]
Anandasundaram et al[43]	2013	Systematic review of 19 observational studies	6465	Atherosclerotic vascular disease was a significant independent predictor of stroke, thromboembolism and mortality in AF patients (P < 0.05)
Steensig et al[44]	2018	Prospective cohort study	12690	CAD was independently associated with increased risk of ischemic stroke in AF patients. Concomitant CAD increased stroke risk by 29% compared to AF patients without CAD [crude IRR of 1.62; (1.41-1.87)]
Steensig et al[6]	2018	Observational cohort study	96430	CAD was an independent predictor of composite endpoints [adjusted IRR, 1.25; (1.06-1.47)] over and above the usual components of vascular disease in CHA2DS2VASC score
Shi et al[36]	2021	Observational cohort study	2335	Risk of stroke was more dependent on underlying atherosclerotic risk factors than AF per say (P < 0.001)

AF: Atrial fibrillation; CAD: Coronary artery disease; CI: Confidence interval; HR: Hazard ratio; IRR: Incidence rate ratio; MACCE: Major adverse cardio-cerebro vascular event; MI: Myocardial infarction; OR: Odds ratio; RCT: Randomized control trial; TIA: Transient ischemic attack.

Table 2 Impact of various antidiabetic agents on the burden of atrial fibrillation and coronary artery disease and their surrogate endpoints

Antidiabetic drug class	Impact on AF burden/ surrogate end points	Impact on CAD burden/ surrogate end points
Insulin[71]	Increased (↑)	Neutral or increased (-/↑)
Metformin[72]	Reduced (↓)	Reduced (↓)
Sulfonylureas[71]	Neutral (-/↑)	Increased (↑↑)
Thiazolidinediones[73]	Reduced or neutral (-/↓)	Increased (↑↑)
DPP-4 inhibitors[74]	Reduced (-/↓)	Reduced (↓)
GLP-1 receptor agonists[75]	Neutral or slightly increased (-/↑)	Reduced (↓↓)
SGLT-2 inhibitors[76]	Reduced (↓↓)	Reduced (↓↓↓)

AF: Atrial fibrillation; CAD: Coronary artery disease; DPP-4: Dipeptidyl peptidase-4; GLP-1: Glucagon-like peptide 1; SGLT-2: Sodium-glucose cotransporter-2.