Effects of Statin Dose, Class, and Use Intensity on All-Cause Mortality in Patients with Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Results
2.1. Association of All-Cause Mortality with Different Statin Dosages and Classes
2.2. Statin Use Intensity
2.3. Sensitivity Analysis
3. Discussion
4. Methods
4.1. Study Population
4.2. Study Covariates
4.3. Outcome Variables
4.4. Statin Use
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nonusers | Users | p | ASMD | |||
---|---|---|---|---|---|---|
N = 427,407 | N = 422,380 | |||||
Characteristic | n | % | n | % | ||
Age, mean ± SD, years | 56.85 ± 20.97 | 56.92 ± 19.24 | 0.8520 | |||
Age, median (IQR), years | 56.00 (46.00, 68.00) | 56.00 (48.00, 68.00) | 0.9999 | |||
Age group, years | 0.0844 | 0.0046 | ||||
≤50 | 143,911 | 33.67% | 141,194 | 33.43% | ||
51–60 | 112,251 | 26.26% | 111,046 | 26.29% | ||
61–70 | 86,430 | 20.22% | 86,057 | 20.37% | ||
≥71 | 84,815 | 19.84% | 84,083 | 19.91% | ||
Sex | 0.6946 | 0.0004 | ||||
Female | 202,041 | 47.27% | 199,485 | 47.23% | ||
Male | 225,366 | 52.73% | 222,895 | 52.77% | ||
Income levels (NTD) | 0.6213 | 0.0008 | ||||
Low income | 6860 | 1.61% | 6702 | 1.59% | ||
Financially dependent | 135,057 | 31.60% | 133,548 | 31.62% | ||
≤20,000 | 202,250 | 47.32% | 200,462 | 47.46% | ||
20,001–30,000 | 38,833 | 9.09% | 38,088 | 9.02% | ||
30,001–45,000 | 28,027 | 6.56% | 27,510 | 6.51% | ||
>45,000 | 16,380 | 3.83% | 16,070 | 3.80% | ||
Urbanization | 0.9444 | 0.0001 | ||||
Rural | 121,995 | 28.54% | 120,589 | 28.55% | ||
Urban | 305,412 | 71.46% | 301,791 | 71.45% | ||
Number of antidiabetic drug types used | 0.0701 | 0.0009 | ||||
0 | 156,611 | 36.64% | 155,804 | 36.89% | ||
1 | 105,742 | 24.74% | 104,725 | 24.79% | ||
2 | 105,362 | 24.65% | 103,280 | 24.45% | ||
3 | 43,350 | 10.14% | 42,551 | 10.07% | ||
≥4 | 16,342 | 3.82% | 16,020 | 3.79% | ||
Antidiabetic drugs used | ||||||
Insulin | 45,219 | 10.58% | 44,743 | 10.59% | 0.9485 | 0.0002 |
Metformin | 183,186 | 43.86% | 181,487 | 42.97% | 0.5920 | 0.0007 |
SU | 206,950 | 48.42% | 204,777 | 48.48% | 0.3972 | 0.0006 |
AGI | 3479 | 0.81% | 3473 | 0.82% | 0.4462 | 0.0001 |
TZD | 27,054 | 6.33% | 26,950 | 6.38% | 0.6642 | 0.0002 |
DPP4i | 21,071 | 4.93% | 20,903 | 4.95% | 0.7950 | 0.0002 |
SGLT2i | 488 | 0.11% | 464 | 0.11% | 0.9429 | 0.0001 |
Others | 24,661 | 5.78% | 24,412 | 5.78% | 0.9652 | 0.0001 |
aDCSI score | ||||||
Mean ± SD | 1.00 ± 1.89 | 1.03 ± 1.44 | 0.5461 | |||
Median (IQR) | 0.00 (0.00, 2.00) | 0.00 (0.00, 2.00) | 0.5659 | |||
aDCSI score | 0.7967 | 0.0059 | ||||
0 | 219,618 | 51.38% | 217,419 | 51.47% | ||
1 | 89,009 | 20.83% | 87,662 | 20.75% | ||
2 | 65,173 | 15.25% | 64,273 | 15.22% | ||
≥3 | 53,607 | 12.54% | 53,026 | 12.55% | ||
Retinopathy | 24,661 | 5.77% | 24,395 | 5.78% | 0.8936 | 0.0004 |
Nephropathy | 50,647 | 11.85% | 50,118 | 11.87% | 0.8851 | 0.0002 |
Neuropathy | 44,450 | 10.40% | 44,130 | 10.45% | 0.3064 | 0.0008 |
Cerebrovascular | 45,518 | 10.65% | 45,226 | 10.71% | 0.7408 | 0.0002 |
Cardiovascular | 113,946 | 26.66% | 113,559 | 26.89% | 0.8863 | 0.0002 |
Peripheral vascular disease | 16,113 | 3.77% | 15,914 | 3.77% | 0.9940 | 0.0001 |
Metabolic disorder | 7738 | 1.81% | 7734 | 1.83% | 0.8046 | 0.0001 |
Comorbidities | ||||||
Hypertension | 219,833 | 51.43% | 217,360 | 51.46% | 0.8053 | 0.0003 |
Coronary artery disease | 96,754 | 22.64% | 95,261 | 22.55% | 0.3541 | 0.0008 |
Stroke | 62,388 | 14.60% | 61,602 | 14.58% | 0.8697 | 0.0001 |
Depression | 28,112 | 6.58% | 28,035 | 6.64% | 0.2645 | 0.0006 |
Anxiety | 59,006 | 13.81% | 58,624 | 13.88% | 0.3245 | 0.0007 |
Heart failure | 28,686 | 6.71% | 28,508 | 6.75% | 0.4897 | 0.0004 |
Peripheral vascular disease | 9221 | 2.16% | 9091 | 2.15% | 0.8691 | 0.0001 |
COPD | 88,209 | 20.64% | 86,839 | 20.56% | 0.3698 | 0.0008 |
Atrial fibrillation | 9495 | 2.22% | 9328 | 2.21% | 0.6841 | 0.0001 |
Traumatic head injury | 26,003 | 6.08% | 25,696 | 6.08% | 0.9955 | 0.0000 |
Hearing loss | 11,359 | 2.66% | 11,365 | 2.69% | 0.3464 | 0.0003 |
Sleep apnea | 2423 | 0.57% | 2349 | 0.56% | 0.5036 | 0.0001 |
Liver cirrhosis | 119,973 | 28.07% | 118,674 | 28.10% | 0.2204 | 0.0023 |
SLE | 6592 | 1.54% | 6547 | 1.55% | 0.7749 | 0.0001 |
CCI scores | ||||||
Mean ± SD | 1.10 ± 2.10 | 1.20 ± 1.58 | 0.1397 | |||
Median (Q1, Q3) | 0.00 (0.00, 2.00) | 1.00 (0.00, 2.00) | 0.9628 | |||
CCI scores | 0.0785 | 0.0019 | ||||
0 | 229,905 | 53.79% | 226,397 | 53.60% | ||
≥1 | 197,503 | 46.21% | 195,983 | 46.40% | ||
Different classes of statins | ||||||
Lipophilic statins | ||||||
Atorvastatin | 0 | 0.00% | 151,553 | 35.88% | ||
Lovastatin | 0 | 0.00% | 30,567 | 7.24% | ||
Simvastatin | 0 | 0.00% | 83,995 | 19.89% | ||
Fluvastatin | 0 | 0.00% | 39,711 | 9.40% | ||
Pitavastatin | 0 | 0.00% | 2830 | 0.67% | ||
Hydrophilic statins | ||||||
Rosuvastatin | 0 | 0.00% | 82,591 | 19.55% | ||
Pravastatin | 0 | 0.00% | 31,134 | 7.37% | ||
cDDD-year of statins | ||||||
Q1 | 0 | 0.00% | 118,541 | 28.06% | ||
Q2 | 0 | 0.00% | 109,873 | 26.01% | ||
Q3 | 0 | 0.00% | 101,282 | 23.98% | ||
Q4 | 0 | 0.00% | 98,684 | 21.94% | ||
DDD | ||||||
≤1 | 0 | 0.00% | 143,141 | 33.89% | ||
>1 | 0 | 0.00% | 279,239 | 66.11% | ||
Stain use | ||||||
New use (after type 2 diabetes diagnosis) | 0 | 0.00% | 384,108 | 90.94% | ||
Prevalent use (before type 2 diabetes diagnosis) | 0 | 0.00% | 38,272 | 9.06% | ||
Time from type 2 diabetes diagnosis to statins exposure | ||||||
Mean ±SD follow-up | 2.42 ± 2.69 | |||||
Median (IQR) follow-up | 1.33 (0.07, 4.19) | |||||
Follow-up duration | ||||||
Mean ± SD follow-up | 8.04 ± 3.12 | 9.48 ± 1.76 | <0.0001 | |||
Median (IQR) follow-up | 8.97 (5.66, 9.33) | 9.65 (7.58, 9.76) | <0.0001 | |||
All-cause mortality | <0.0001 | |||||
No | 308,643 | 72.21% | 371,576 | 87.97% | ||
Yes | 118,765 | 27.79% | 50,804 | 12.03% |
Variables | Crude HR (95%CI) | p | aHR (95%CI) * | p | ||
---|---|---|---|---|---|---|
Stain user or nonusers | ||||||
Nonusers | Reference | |||||
Users | 0.37 | (0.36, 0.37) | <0.0001 | 0.32 | (0.31, 0.33) | <0.0001 |
Different classes of statins | ||||||
Nonusers | Reference | |||||
Hydrophilic statins | ||||||
Rosuvastatin | 0.32 | (0.31, 0.34) | <0.0001 | 0.29 | (0.28, 0.31) | <0.0001 |
Pravastatin | 0.31 | (0.3, 0.32) | <0.0001 | 0.28 | (0.27, 0.29) | <0.0001 |
Lipophilic statins | ||||||
Atorvastatin | 0.05 | (0.03, 0.07) | <0.0001 | 0.06 | (0.04, 0.09) | <0.0001 |
Lovastatin | 0.47 | (0.45, 0.48) | <0.0001 | 0.36 | (0.35, 0.38) | <0.0001 |
Simvastatin | 0.34 | (0.33, 0.35) | <0.0001 | 0.31 | (0.30, 0.32) | <0.0001 |
Fluvastatin | 0.58 | (0.56, 0.61) | <0.0001 | 0.48 | (0.47, 0.50) | <0.0001 |
Pitavastatin | 0.36 | (0.36, 0.37) | <0.0001 | 0.31 | (0.31, 0.32) | <0.0001 |
cDDD-year of statins | ||||||
Nonusers | Reference | |||||
Q1 | 0.61 | (0.6, 0.62) | <0.0001 | 0.51 | (0.5, 0.52) | <0.0001 |
Q2 | 0.41 | (0.4, 0.42) | <0.0001 | 0.36 | (0.35, 0.37) | <0.0001 |
Q3 | 0.27 | (0.26, 0.27) | <0.0001 | 0.24 | (0.23, 0.25) | <0.0001 |
Q4 | 0.15 | (0.14, 0.15) | <0.0001 | 0.13 | (0.13, 0.14) | <0.0001 |
p for trend | <0.0001 | <0.0001 |
Subpopulation or Exposure | No. of Patients | All-Cause Mortality | |||
---|---|---|---|---|---|
No. of Deaths | aHR * | 95% CI | p | ||
Age group, years | |||||
≤50 | 285,105 | 23,316 | 0.29 | (0.28–0.30) | <0.0001 |
51–60 | 223,297 | 27,319 | 0.31 | (0.30–0.32) | <0.0001 |
61–70 | 172,487 | 37,672 | 0.33 | (0.32–0.34) | <0.0001 |
≥71 | 168,898 | 81,260 | 0.32 | (0.32–0.33) | <0.0001 |
Sex | |||||
Female | 401,526 | 68,131 | 0.3 | (0.30–0.31) | <0.0001 |
Male | 448,261 | 101,438 | 0.33 | (0.33–0.34) | <0.0001 |
Income levels (NTD) | |||||
Low income | 13,562 | 4936 | 0.35 | (0.32–0.38) | <0.0001 |
Financially dependent | 268,604 | 62,198 | 0.33 | (0.32–0.33) | <0.0001 |
≤20,000 | 402,713 | 90,946 | 0.31 | (0.31–0.32) | <0.0001 |
20,001–30,000 | 76,921 | 5847 | 0.34 | (0.31–0.36) | <0.0001 |
30,001–45,000 | 55,537 | 3713 | 0.32 | (0.29–0.35) | <0.0001 |
>45,000 | 32,450 | 1928 | 0.41 | (0.36–0.47) | <0.0001 |
Urbanization | |||||
Rural | 242,584 | 58,568 | 0.31 | (0.30–0.32) | <0.0001 |
Urban | 607,203 | 111,001 | 0.33 | (0.32–0.33) | <0.0001 |
Number of antidiabetic drug types used | |||||
0 | 312,415 | 50,615 | 0.33 | (0.32–0.34) | <0.0001 |
1 | 210,467 | 43,730 | 0.30 | (0.29–0.31) | <0.0001 |
2 | 208,642 | 40,260 | 0.33 | (0.32–0.34) | <0.0001 |
3 | 85,901 | 24,499 | 0.31 | (0.30–0.32) | <0.0001 |
≥4 | 32,362 | 10,464 | 0.33 | (0.31–0.35) | <0.0001 |
aDCSI score | |||||
0 | 437,037 | 53,522 | 0.31 | (0.31–0.32) | <0.0001 |
1 | 176,671 | 27,167 | 0.36 | (0.34–0.37) | <0.0001 |
2 | 129,446 | 39,528 | 0.29 | (0.28–0.30) | <0.0001 |
≥3 | 106,633 | 49,352 | 0.33 | (0.32–0.34) | <0.0001 |
CCI scores | |||||
0 | 437,037 | 53,522 | 0.31 | (0.31–0.32) | <0.0001 |
≥1 | 393,486 | 105,134 | 0.30 | (0.29–0.30) | <0.0001 |
Coexisting comorbidities | |||||
Hypertension | 437,193 | 112,774 | 0.33 | (0.32–0.34) | <0.0001 |
Coronary artery disease | 192,015 | 50,785 | 0.30 | (0.29–0.31) | <0.0001 |
Stroke | 123,990 | 58,964 | 0.34 | (0.33–0.34) | <0.0001 |
Depression | 56,147 | 13,352 | 0.32 | (0.30–0.34) | <0.0001 |
Anxiety | 117,630 | 24,118 | 0.33 | (0.31–0.34) | <0.0001 |
Heart failure | 57,194 | 27,547 | 0.32 | (0.31–0.34) | <0.0001 |
Peripheral vascular disease | 18,312 | 6472 | 0.34 | (0.31–0.36) | <0.0001 |
COPD | 175,048 | 56,398 | 0.31 | (0.30–0.32) | <0.0001 |
Atrial fibrillation | 18,823 | 10,415 | 0.35 | (0.33–0.37) | <0.0001 |
Traumatic head injury | 51,699 | 15,134 | 0.29 | (0.27–0.30) | <0.0001 |
Hearing loss | 22,724 | 6519 | 0.32 | (0.30–0.35) | <0.0001 |
Sleep apnea | 4772 | 840 | 0.33 | (0.27–0.42) | <0.0001 |
Liver cirrhosis | 237,795 | 46,407 | 0.29 | (0.28–0.30) | <0.0001 |
SLE | 13,139 | 2879 | 0.31 | (0.27–0.34) | <0.0001 |
DDD | |||||
≤1 | 560,998 | 137,268 | 0.36 | (0.35–0.37) | <0.0001 |
>1 | 288,789 | 32,300 | 0.50 | (0.46–0.53) | <0.0001 |
Stain use | |||||
New use (after type 2 diabetes diagnosis) | 803,889 | 159,321 | 0.31 | (0.31–0.32) | <0.0001 |
Prevalent use (before type 2 diabetes diagnosis) | 45,898 | 10,247 | 0.28 | (0.26–0.29) | <0.0001 |
Metformin use | 357,572 | 69,229 | 0.35 | (0.34–0.36) | <0.0001 |
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Yu, J.-M.; Chen, W.-M.; Chen, M.; Shia, B.-C.; Wu, S.-Y. Effects of Statin Dose, Class, and Use Intensity on All-Cause Mortality in Patients with Type 2 Diabetes Mellitus. Pharmaceuticals 2023, 16, 507. https://doi.org/10.3390/ph16040507
Yu J-M, Chen W-M, Chen M, Shia B-C, Wu S-Y. Effects of Statin Dose, Class, and Use Intensity on All-Cause Mortality in Patients with Type 2 Diabetes Mellitus. Pharmaceuticals. 2023; 16(4):507. https://doi.org/10.3390/ph16040507
Chicago/Turabian StyleYu, Jung-Min, Wan-Ming Chen, Mingchih Chen, Ben-Chang Shia, and Szu-Yuan Wu. 2023. "Effects of Statin Dose, Class, and Use Intensity on All-Cause Mortality in Patients with Type 2 Diabetes Mellitus" Pharmaceuticals 16, no. 4: 507. https://doi.org/10.3390/ph16040507