Table 2.

Sudden cardiac death by study exposures, nested case-control analysis: results of unadjusted and multivariable conditional logistic regression

Exposure category (categories are mutually exclusive)	SCD cases [N = 3239]		Controls [N = 12,572]		Matched ORa	95 % CI	Adjusted ORb	95 % CI
	N	%	N	%
Reference level: no exposure to any study drug
Current exposure to domperidonec	28	0.9	52	0.4	3.23	2.02–5.16	1.71	0.92–3.18
Current exposure to PPI	1935	59.7	6499	51.7	1.72	1.57–1.89	1.35	1.21–1.51
Current exposure to metoclopramide	37	1.1	44	0.3	5.15	3.29–8.06	4.31	2.33–7.98
Current combined exposured	96	3.0	154	1.2	3.62	2.77–4.73	2.68	1.87–3.83
Past exposure to any study drug	341	10.5	1330	10.6	1.47	1.27–1.70	1.20	1.01–1.43
No exposure to any study drug	802	24.8	4493	35.7	Reference		Reference
Reference level: current exposure to PPI
Current exposure to domperidonec	28	0.9	52	0.4	1.88	1.18–2.99	1.26	0.68–2.34
Current exposure to PPI	1935	59.7	6499	51.7	Reference		Reference
Current exposure to metoclopramide	37	1.1	44	0.3	2.99	1.92–4.65	3.19	1.73–5.88
Current combined exposured	96	3.0	154	1.2	2.10	1.62–2.73	1.98	1.40–2.81
Past exposure to any study drug	341	10.5	1330	10.6	0.85	0.75–0.97	0.89	0.75–1.05
No exposure to any study drug	802	24.8	4493	35.7	0.58	0.53–0.64	0.74	0.66–0.83
Reference level: current exposure to metoclopramide
Current exposure to domperidonec	28	0.9	52	0.4	0.63	0.33–1.18	0.40	0.17–0.94
Current exposure to PPI	1935	59.7	6499	51.7	0.33	0.21–0.52	0.31	0.17–0.58
Current exposure to metoclopramide	37	1.1	44	0.3	Reference		Reference
Current combined exposured	96	3.0	154	1.2	0.70	0.42–1.17	0.62	0.31–1.25
Past exposure to any study drug	341	10.5	1330	10.6	0.29	0.18–0.45	0.28	0.15–0.52
No exposure to any study drug	802	24.8	4493	35.7	0.19	0.12–0.30	0.23	0.13–0.43

OR odds ratio, CI confidence interval, PPI proton pump inhibitor, SCD sudden cardiac death, BMI body mass index, GP general practitioner, hERG human Ether-à-go-go-Related Gene

^aOR matched for age, sex, and practice. The 12,572 controls were matched to cases as follows: 70 cases with one control each, 54 cases with two controls each, 66 cases with three controls each, and 3049 cases with four controls each. Twenty-eight cases and 52 controls were exposed solely to domperidone at the index date

^bOR matched for age, sex, and practice, and adjusted for the following covariates: history of serious ventricular arrhythmia, myocardial infarction, heart failure, valvular heart disease including valve replacement, cardiomyopathy, other arrhythmia or conduction disorder, epilepsy, depression, group 2 QTc-prolonging drugs, drugs that affect hERG, digoxin, diuretics, laxatives, β-blockers, BMI, alcohol use, smoking history, number of GP visits, and number of hospital admissions

^cIncludes one case and one control with rectal exposure to domperidone

^dCurrent exposure to more than one study drug: domperidone + PPI, domperidone + metoclopramide, PPI + metoclopramide, or domperidone + PPI + metoclopramide