Risk of Mortality (including Sudden Cardiac Death) and Major Cardiovascular Events in Users of Olanzapine and Other Antipsychotics: A Study with the General Practice Research Database

Table 5

Relative risks of all-cause mortality (excluding suicide) and cardiovascular outcomes for current users of various types of antipsychotics versus nonuser psychiatric controls stratified by dose.

Outcome	Exposure type of current users	Dose	Outcome events	Person-time (Years)	Incidence rate per 1000 PY; (95% CI)	Fully adjusted RR (aRR); (95% CI)
All-cause mortality	Nonuser psychiatric	NA	7765	307,276	25.3 (24.7–25.8)	Reference
	Atypical or typical	Low	21,208	218,635	97.0 (95.7–98.3)	1.72 (1.62–1.84)^‡
		Medium	1978	37,704	52.5 (50.2–54.8)	1.94 (1.80–2.10)^‡
		High	655	20,553	31.9 (29.5–34.4)	1.89 (1.71–2.09)^‡
	Atypical	Low	5969	51,838	115.2 (112.3–118.1)	1.51 (1.40–1.64)^‡
		Medium	1106	28,874	38.3 (36.1–40.6)	1.54 (1.40–1.69)^‡
		High	281	13,401	21.0 (18.6–23.6)	1.48 (1.29–1.71)^‡
	Typical	Low	14,528	160,264	90.7 (89.2–92.1)	1.76 (1.63–1.89)^‡
		Medium	683	4232	161.4 (149.5–174.0)	3.74 (3.36–4.15)^‡
		High	262	2509	104.4 (92.2–117.9)	3.61 (3.14–4.16)^‡
	Olanzapine	Low	873	17,172	50.8 (47.5–54.3)	1.00 (0.88–1.13)
		Medium	323	12,304	26.3 (23.5–29.3)	1.07 (0.92–1.24)
		High	109	5509	19.8 (16.3–23.9)	1.20 (0.97–1.49)*
Cardiac Mortality	Nonuser psychiatric	NA	1289	200,988	6.4 (6.1–6.8)	Reference
	Atypical or typical	Low	2157	107,874	20.0 (19.2–20.9)	1.65 (1.36–2.00)^‡
		Medium	251	25,299	9.9 (8.7–11.2)	2.10 (1.68–2.63)^‡
		High	70	12,470	5.6 (4.4–7.1)	2.27 (1.68–3.07)^‡
	Atypical	Low	984	42,824	23.0 (21.6–24.5)	1.35 (1.24–1.47)^‡
		Medium	173	21,258	8.1 (7.0–9.5)	1.67 (1.42–1.97)^‡
		High	43	9202	4.7 (3.4–6.3)	1.84 (1.35–2.51)^‡
	Typical	Low	1108	61,999	17.9 (16.8–19.0)	1.82 (1.44–2.32)^‡
		Medium	57	1862	30.6 (23.2–39.7)	3.40 (2.39–4.83)^‡
		High	15	1053	14.3 (8.0–23.5)	3.13 (1.79–5.47)^‡
	Olanzapine	Low	129	13,897	9.3 (7.8–11.0)	1.31 (0.93–1.82)
		Medium	60	8851	6.8 (5.2–8.7)	2.06 (1.41–3.01)^‡
		High	17	4016	4.2 (2.5–6.8)	2.37 (1.36–4.12)^‡
SCD (secondary definition)	Nonuser psychiatric	NA	98	23,873	4.1 (3.3–5.0)	Reference
	Atypical or typical	Low	157	11,914	13.2 (11.2–15.4)	2.09 (1.60–2.75)^‡
		Medium	14	2956	4.7 (2.6–8.0)	2.42 (1.35–4.35)^‡
		High	7	1274	5.5 (2.2–11.3)	3.36 (1.50–7.50)^‡
	Atypical	Low	82	6469	12.7 (10.1-15.7)	1.78 (1.31–2.42)^‡
		Medium	6	2660	2.3 (0.8–4.9)	1.32 (0.57–3.05)
		High	2	1072	1.9 (0.2–6.7)	1.53 (0.37–6.39)
	Typical	Low	70	5202	13.5 (10.5–17.0)	2.48 (1.81–3.40)^‡
		Medium	5	156	32.1 (10.4–74.8)	6.07 (2.45–14.99)^‡
		High	3	57	52.8 (10.9–154.3)	10.05 (3.15–32.08)^‡
	Olanzapine	Low	8	1951	4.1 (1.8–8.1)	0 (NC)
		Medium	2	1052	1.9 (0.2–6.9)	0 (NC)
		High	0	451	0.0 (0.0-8.2)	0 (NC)
CHD	Nonuser psychiatric	NA	982	278,330	3.5 (3.3–3.8)	Reference
	Atypical or typical	Low	1192	185,032	6.4 (6.1–6.8)	1.19 (0.96–1.48)
		Medium	126	33,440	3.8 (3.1–4.5)	1.15 (0.88–1.50)
		High	37	17,757	2.1 (1.5 –2.9)	0.86 (0.59–1.26)
	Atypical	Low	328	48,223	6.8 (6.1–7.6)	0.94 (0.72–1.23)
		Medium	95	26,059	3.7 (3.0–4.5)	1.11 (0.81–1.51)
		High	21	11,833	1.8 (1.1–2.7)	0.77 (0.47–1.26)
	Typical	Low	843	131,363	6.4 (6.0–6.9)	1.40 (1.10–1.78)^‡
		Medium	20	3413	5.9 (3.6–9.1)	1.25 (0.76–2.05)
		High	10	2001	5.0 (2.4–9.2)	1.54 (0.80–2.98)
	Olanzapine	Low	76	15,856	4.8 (3.8–6.0)	0.99 (0.68–1.45)
		Medium	46	11,029	4.2 (3.1–5.6)	1.34 (0.89–2.01)
		High	10	4921	2.0 (1.0–3.7)	0.82 (0.42–1.63)
Ventricular arrhythmias	Nonuser psychiatric	NA	500	279,243	1.8 (1.6–2.0)	Reference
	Atypical or typical	Low	540	186,417	2.9 (2.7–3.2)	1.13 (0.99–1.29)*
		Medium	70	33,445	2.1 (1.6–2.6)	1.27 (0.98–1.64)*
		High	36	17,784	2.0 (1.4–2.8)	1.55 (1.08–2.20)^†
	Atypical	Low	163	48,398	3.4 (2.9–3.9)	1.03 (0.85–1.24)
		Medium	48	26,079	1.8 (1.4–2.4)	1.12 (0.83–1.51)
		High	19	11,842	1.6 (1.0–2.5)	1.27 (0.79–2.02)
	Typical	Low	359	132,550	2.7 (2.4–3.0)	1.13 (0.98–1.31)*
		Medium	16	3416	4.7 (2.7–7.6)	2.23 (1.35–3.69)^‡
		High	7	2017	3.5 (1.4–7.2)	2.11 (0.99–4.47)*
	Olanzapine	Low	33	15,926	2.1 (1.4–2.9)	0.84 (0.59–1.20)
		Medium	14	11,068	1.3 (0.7–2.1)	0.78 (0.46–1.33)
		High	8	4927	1.6 (0.7–3.2)	1.22 (0.60–2.46)

^∗𝑃<0.10, ^†𝑃<0.05, ^‡𝑃<0.01.
Abbreviations: aRR: adjusted relative risk; CHD: coronary heart disease; CI: confidence interval; NC: not calculable; PY: person-years; SCD: sudden cardiac death.