Introduction
Methods
Study design
The Health Improvement Network (THIN) Database
Study participants
Follow-up and endpoints
Baseline and endpoint characteristics
Statistical analysis
Subgroup analysis
Results
Patient characteristics, cases and total follow up
Statin use | None | Total | p value | |
---|---|---|---|---|
(n = 10,682) | (n = 2043) | (n = 12,725) | ||
Demographics | ||||
Age (years). mean (SD) | 59.4 (12.7) | 54.3 (18.2) | 58.6 (13.8) | <0.001 |
Gender. no. (%) | ||||
Female | 5258 (49) | 1122 (55) | 6380 (50) | <0.001 |
Smoking status. no (%) | ||||
Non-smoker | 5549 (52) | 1137 (56) | 6686 (52) | |
Ex-smoker | 3634 (34) | 543 (27) | 4177 (33) | <0.001 |
Current | 1499 (14) | 363 (18) | 1862 (15) | |
Alcohol status. no (%) | ||||
Never | 3431 (32) | 614 (30) | 4045 (32) | |
Ex-drinker | 1133 (11) | 320 (16) | 1453 (11) | <0.001 |
Current | 6118 (57) | 1109 (54) | 7227 (57) | |
Deprivation. no (%) | ||||
Least deprived | 2151 (21) | 403 (21) | 2554 (20) | |
Second quintile | 2089 (20) | 382 (20) | 2471 (19) | |
Third quintile | 2255 (22) | 422 (22) | 2677 (21) | 0.631 |
Fourth quintile | 2171 (21) | 399 (21) | 2570 (20) | |
Most deprived | 1591 (16) | 327 (17) | 1918 (15) | |
Clinical parameters. mean (SD) | ||||
HbA1c (%) | 8.7 (1.8) | 8.7 (2.0) | 8.7 (1.8) | 0.556 |
BMI (kg/m2) | 32.7 (6.9) | 32.8 (7.2) | 32.7 (6.9) | 0.252 |
Diabetes durationa (years) | 4.0 (4.9) | 2.5 (4.3) | 3.8 (4.9) | <0.001 |
Time on insulin (years) | 3.7 (6.3) | 2.3 (6.0) | 3.5 (6.3) | <0.001 |
Height (m) | 1.7 (0.1) | 1.7 (0.1) | 1.7 (0.1) | 0.860 |
Weight (kg) | 91.4 (18.8) | 91.9 (19.1) | 91.5 (18.8) | 0.268 |
DBP (mmHg) | 76.5 (10.8) | 76.9 (11.1) | 76.6 (10.9) | 0.129 |
SBP (mmHg) | 136.4 (23.0) | 134.6 (23.4) | 136.1 (23.1) | 0.002 |
Albumin (g/L) | 4.1 (0.4) | 4.0 (0.4) | 4.1 (0.4) | 0.002 |
ACR (mg/mol) | 5.7 (8.4) | 5.2 (8.5) | 5.6 (8.5) | 0.014 |
eGFR (mLs/min/1.73 m2) | 64.6 (21.0) | 68.0 (22.0) | 65.1 (21.2) | <0.001 |
TC. (mmol/L) | 4.6 (1.3) | 4.7 (1.4) | 4.6 (1.3) | <0.001 |
Triglyceride (mmol/L) | 2.0 (1.2) | 2.0 (1.2) | 2.0 (1.2) | 0.072 |
LDL (mmol/L) | 2.4 (1.1) | 2.5 (1.1) | 2.4 (1.1) | <0.001 |
HDL (mmol/L) | 1.3 (0.5) | 1.3 (0.5) | 1.3 (0.5) | 0.225 |
BMI categories, no. (%) | ||||
Normal | 1371 (13) | 294 (14) | 1665 (13) | |
Overweight | 2533 (24) | 489 (24) | 3022 (24) | 0.131 |
Obese | 6778 (63) | 1260 (62) | 8038 (63) | |
Use of medications, no. (%) | ||||
Aspirin | 10,481 (95) | 1541 (94) | 12,022 (94) | 0.723 |
Antihypertensives | 9321 (87) | 1217 (91) | 10,538 (83) | <0.001 |
GLTsb no (%) | ||||
Dual Therapy | 2334 (22) | 904 (44) | 3238 (28) | |
Triple Therapy | 3400 (33) | 609 (30) | 4009 (33) | <0.001 |
More than triple therapy | 4948 (45) | 669 (26) | 5478 (39) | |
Comorbidities, no. (%) | ||||
Hypoglycaemia | 1824 (17) | 313 (15) | 2137 (17) | 0.052 |
Heart failure | 641 (6) | 72 (4) | 713 (6) | <0.001 |
PAD | 756 (7) | 67 (3) | 823 (7) | <0.001 |
CHD | 1390 (13) | 75 (4) | 1465 (12) | <0.001 |
Primary endpoints: metabolic outcomes
Association between prior statin use and glycaemic response
Relationship between statin use and other clinical measurements
Secondary endpoints: risk of major adverse cardiovascular events (3-point MACE)
Crude event rates
Statin use (N = 10,682) | None (N = 2043) | |
---|---|---|
Composite outcomea
| ||
No of events/person-years | 878/42,484 | 217/7032 |
Absolute ratesb (95% CI) | 20.7 (19.3–22.1) | 30.9 (27.0–35.3) |
HRc (95% CI) | 1 (reference) | 1.53 (1.32–1.77) |
aHRd (95% CI) | 1 (reference) | 1.36 (1.15–1.62) |
All-cause mortality | ||
No of events/person-years | 415/43,503 | 177/7098 |
Absolute rates (95% CI) | 9.5 (8.7–10.5) | 24.9 (21.5–28.9) |
HR (95% CI) | 1 (reference) | 2.61 (2.19–3.12) |
aHR (95% CI) | 1 (reference) | 1.89 (1.51–2.37) |
Acute myocardial infarction (AMI) | ||
No of events/person-years | 60/43,377 | 5/7094 |
Absolute rates (95% CI) | 1.4 (1.1–1.8) | 0.7 (0.3–1.7) |
HR (95% CI) | 1 (reference) | 0.50 (0.20–1.25) |
aHR (95% CI) | 1 (reference) | 0.88 (0.35–2.23) |
Non-fatal stroke | ||
No of events/person-years | 401/42,643 | 34/7051 |
Absolute rates (95% CI) | 9.4 (8.5–10.4) | 4.8 (3.4–6.7) |
HR (95% CI) | 1 (reference) | 0.51 (0.36–0.72) |
aHR (95% CI) | 1 (reference) | 0.55 (0.38–0.81) |
Risk of 3-point composite of MACE
Subgroup and sensitivity analyses
None | Atorvastatin | Simvastatin | Rosuvastatin | Pravastatin | |
---|---|---|---|---|---|
(N = 2043) | (N = 4415) | (N = 4462) | (N = 713) | (N = 1092) | |
Composite outcomea
| |||||
No of events/person-years | 217/7032 | 398/16,840 | 342/18,287 | 41/2894 | 97/4461 |
Absolute ratesb (95% CI) | 30.9 (27.0–35.3) | 23.6 (21.4–26.1) | 18.7 (16.8–20.8) | 14.2 (10.4–19.2) | 21.7 (17.8–26.5) |
HRc (95% CI) | 1 (reference) | 0.75 (0.64–0.89) | 0.59 (0.50–0.70) | 0.45 (0.32–0.62) | 0.68 (0.54–0.87) |
aHRd (95% CI) | 1 (reference) | 0.82 (0.68–0.98) | 0.67 (0.55–0.82) | 0.56 (0.39–0.81) | 0.78 (0.60–1.01) |
All-cause mortality | |||||
No of events/person-years | 177/7098 | 203/17,229 | 162/18,710 | 17/2947 | 33/4616 |
Absolute rates (95% CI) | 24.9 (21.5–28.9) | 11.8 (10.3–13.5) | 8.7 (7.4–10.1) | 5.8 (3.6–9.3) | 7.1 (5.1–10.1) |
HR (95% CI) | 1 (reference) | 0.45 (0.37–0.55) | 0.32 (0.26–0.40) | 0.22 (0.13–0.36) | 0.27 (0.19–0.39) |
aHR (95% CI) | 1 (reference) | 0.61 (0.48–0.78) | 0.49 (0.38–0.64) | 0.39 (0.22–0.67) | 0.39 (0.26–0.60) |
Acute myocardial infarction (AMI) | |||||
No of events/person-years | 5/7094 | 26/17,168 | 21/18,670 | 2/2948 | 11/4590 |
Absolute rates (95% CI) | 0.7 (0.3–1.7) | 1.5 (1.0–2.2) | 1.1 (0.7–1.7) | 0.7 (0.2–2.7) | 2.4 (1.3–4.3) |
HR (95% CI) | 1 (reference) | 2.17 (0.83–5.65) | 1.62 (0.61–4.30) | 0.98 (0.19–5.03) | 3.45 (1.20–9.94) |
aHR (95% CI) | 1 (reference) | 1.42 (0.53–3.78) | 0.88 (0.32–2.40) | 0.63 (0.12–3.33) | 1.61 (0.54–3.78) |
Non-fatal stroke | |||||
No of events/person-years | 34/7051 | 168/16,919 | 158/18,337 | 22/2896 | 53/4489 |
Absolute rates (95% CI) | 4.8 (3.4–6.7) | 9.9 (8.5–11.6) | 8.6 (7.4–10.1) | 7.6 (5.0–11.5) | 11.8 (9.0–15.5) |
HR (95% CI) | 1 (reference) | 2.07 (1.43–2.99) | 1.80 (1.24–2.61) | 1.59 (0.93–2.72) | 2.47 (1.61–3.80) |
aHR (95% CI) | 1 (reference) | 1.82 (1.22–2.72) | 1.67 (1.11–2.51) | 1.64 (0.91–2.94) | 2.42 (1.52–3.84) |