Hypertension is a common chronic condition which is associated with various complications including cardiovascular disease and chronic kidney disease. It remains that hypertension is one of the most important preventable conditions to reduce cardiovascular mortality [
In order to choose the appropriate antihypertensive drug among various available classes, several factors should be considered, such as age and underlying comorbid conditions [
This study aimed at evaluating prescribing patterns of antihypertensive drugs in patients who were prescribed antihypertensive drugs for the first time.
The claims data of the Korean National Health Insurance Research Database (NHIRD) were analyzed. NHIRD contains qualification data, medical services claim data, and pharmacy claim data. As such, the claims data include patient information such as age, sex, household income, residential regions, as well as diagnosis information (by the International Classification of Diseases, 10th Revision; ICD-10) and specific information of diagnostic tests, procedures, and prescriptions.
In general, the Korean National Health Insurance Service (NHIS) is the sole insurer providing a mandatory universal health insurance which virtually covers the entire Korean population (about 97% of total population) and a medical aid program to those in the lowest income bracket who are covered by government funding. We used the nation-wide claims data which covered the South Korean population over a 5-year period, from 1 January 2011 to 31 December 2015. Detailed insights into the advantages of this data are described elsewhere [
From the whole Korean population (
Antihypertensive agents were classified into 5 major categories, including angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), calcium channel blockers (CCB), beta-blockers (BB), and thiazide diuretics (including indapamide and chlorthalidone), or other antihypertensive drugs.
Initial prescription was divided into single drug and combination. Single drug was defined as the prescription of 1 class of antihypertensive at first prescription. Combination was defined as prescription of 2 or more classes of antihypertensives at first prescription and was further categorized by single-pill fixed-dose drug and free combination (multiple-pill combinations). Commonly used combinations available commercially are specifically listed: ARB + CCB, ARB + thiazide, and ARB + CCB + thiazide.
Comorbidities were defined by ICD 10 codes: diabetes (ICD 10: E11-14), dyslipidemia (E78), congestive heart failure (I50), coronary heart disease(I20-25), stroke (I60 to I64, I67, and I69), chronic kidney disease (N18), and cancer (CX) during the previous 1 year prior to index date (first prescription of antihypertensive medication). The Charlson comorbidity index was also assessed in the same manner [
The baseline characteristics of hypertensive patients who were newly prescribed with antihypertensive medication were described using frequencies and percentages or as means with standard deviation.
Descriptive statistics were calculated for patterns of first prescriptions of antihypertensive medications. The proportion of each antihypertensive class was calculated according to patient characteristics (age, sex, income level, and place of residence), medical characteristics (the Charlson comorbidity index and each comorbidity as defined above), provider characteristics (level of hospital; general hospital vs. hospital vs. clinic), and year of first prescription.
Factors associated with choice of first prescription for hypertension were investigated with a series of multivariate logistic regression analyses including all of the aforementioned characteristics. Outcomes were (1) combination vs. single, (2) choice of each drug class among single drug user (exclusive to each other), (3) choice of each drug class among all patients (not exclusive to each other), and (4) fixed-dose combination vs. free combination for selected combinations. Also, the trends of combination therapy according to the age group, income level, and Charlson’s comorbidity index were assessed by calculating the “
All analyses were performed using the SAS statistical software (ver. 9.3, SAS Institute., Cary, NC, USA). All tests were two-sided, and statistical significance was defined as a
This study was reviewed and approved by the Institutional Review Board of the Samsung Medical Center (IRB No. SMC 2007-07-130). The requirement for informed consent was waived because this study is based on routinely collected administrative or claims data.
A total of 2,919,162 subjects had started taking antihypertension medications during the study period. 56.0% of these were male patients. The mean age of the study population was 53.0 (±14.5) years. Over half of the study population resided in metropolitan areas. About 67.9% of subjects had 1 or more comorbidity as per the Charlson comorbidity index. Subjects had various hypertension-related comorbid conditions such as dyslipidemia (27.6%), coronary heart disease (13.8%), diabetes (12.7%), stroke, (4.6%), congestive heart failure (4.1%), and chronic kidney disease (0.93%). The annual incidence rate per year was 1.24% in 2011, 1.20% in 2012, 1.13% in 2013, 1.05% in 2014, and 1.12% in 2015, respectively (Table
Baseline characteristics of newly diagnosed hypertension patients (total
|
% | |
---|---|---|
Age | ||
<20 | 45,222 | 1.55 |
20–29 | 95,489 | 3.27 |
30–39 | 303,523 | 10.40 |
40–49 | 713,524 | 24.44 |
50–59 | 866,370 | 29.68 |
60–69 | 508,662 | 17.42 |
70–79 | 294,771 | 10.10 |
≥80 | 91,601 | 3.14 |
Sex | ||
Male | 1,633,768 | 55.97 |
Female | 1,285,394 | 44.03 |
Income | ||
Medical aid | 112,217 | 3.84 |
Q1 (low) | 766,378 | 26.25 |
Q2 | 696,643 | 23.86 |
Q3 | 663,524 | 22.73 |
Q4 (high) | 680,400 | 23.31 |
Residence | ||
Metropolitan | 1,741,304 | 59.65 |
City | 833,767 | 28.56 |
Rural | 344,091 | 11.79 |
Charlson comorbidity index | ||
0 | 938,134 | 32.14 |
1 | 791,388 | 27.11 |
2 | 497,523 | 17.04 |
≥3 | 692,117 | 23.71 |
Provider type | ||
General hospital | 924,592 | 31.67 |
Hospital | 330,928 | 11.34 |
Clinic | 1,560,700 | 53.46 |
Others (public health centers, etc.) | 102,942 | 3.53 |
Comorbidity | ||
Diabetes | 371,477 | 12.73 |
Dyslipidemia | 806,246 | 27.62 |
Congestive heart failure | 120,749 | 4.14 |
Ischemic heart failure | 401,547 | 13.76 |
Stroke | 135,569 | 4.64 |
Chronic kidney disease | 27,263 | 0.93 |
Cancer | 44,626 | 1.53 |
Year of diagnosis | ||
2011 | 627,249 | 21.49 |
2012 | 597,912 | 20.48 |
2013 | 578,479 | 19.82 |
2014 | 538,468 | 18.45 |
2015 | 577,054 | 19.77 |
Around two-thirds of the study population was prescribed with monotherapy at first prescription, and one-third was prescribed with initial combination therapy (Table
Prescription pattern by the number of drug classes,
Single drug class | Combination | Combination (vs. single) | |
---|---|---|---|
OR (95% CI) | |||
Overall | 1,947,796 (66.72) | 971366 (33.28) | |
Age (mean ± SD) | 53.13 ± 14.48 | 52.84 ± 14.52 | |
<20 | 29,435 (65.09) | 15,787 (34.91) | 1.214 (1.190–1.239) |
20–29 | 72,099 (75.51) | 23,390 (24.49) | 0.650 (0.640–0.661) |
30–39 | 202,994 (66.88) | 100,529 (33.12) | 0.957 (0.948–0.965) |
40–49 | 458,093 (64.2) | 255,431 (35.8) | 1.094 (1.087–1.101) |
50–59 | 574,198 (66.28) | 292,172 (33.72) | 1 (ref.) |
60–69 | 348,811 (68.57) | 159,851 (31.43) | 0.900 (0.894–0.907) |
70–79 | 202,102 (68.56) | 92,669 (31.44) | 0.913 (0.905–0.922) |
≥80 | 60,064 (65.57) | 31,537 (34.43) | 1.041 (1.026–1.057) |
Sex | |||
Male | 1,048,973 (64.21) | 584,795 (35.79) | 1 (ref.) |
Female | 898,823 (69.93) | 386,571 (30.07) | 0.764 (0.760–0.768) |
Income | |||
Medical aid | 75,202 (67.01) | 37,015 (32.99) | 1.133 (1.118–1.149) |
Q1(Low) | 499,304 (65.15) | 267,074 (34.85) | 1.220 (1.212–1.229) |
Q2 | 457,765 (65.71) | 238,878 (34.29) | 1.184 (1.175–1.193) |
Q3 | 444,104 (66.93) | 219,420 (33.07) | 1.115 (1.107–1.123) |
Q4(High) | 471,421 (69.29) | 208,979 (30.71) | 1 (ref.) |
Residence | |||
Metropolitan | 1,172,041 (67.31) | 569,263 (32.69) | 1 (ref.) |
City | 549,150 (65.86) | 284,617 (34.14) | 1.068 (1.062–1.074) |
Rural | 226,605 (65.86) | 117,486 (34.14) | 1.077 (1.069–1.086) |
Charlson’s comorbidity index | |||
0 | 616,812 (65.75) | 321,322 (34.25) | 1.050 (1.041–1.058) |
1 | 531,229 (67.13) | 260,159 (32.87) | 0.999 (0.992–1.007) |
2 | 338,054 (67.95) | 159,469 (32.05) | 0.962 (0.955–0.970) |
≥3 | 461,701 (66.71) | 230,416 (33.29) | 1 (ref.) |
Comorbidity | |||
Diabetes | 258,962 (69.71) | 112,515 (30.29) | 0.816 (0.810–0.823) |
Dyslipidemia | 528,199 (65.51) | 278,047 (34.49) | 1.107 (1.101–1.114) |
Congestive heart failure | 65,091 (53.91) | 55,658 (46.09) | 1.890 (1.867–1.914) |
Ischemic heart failure | 257,083 (64.02) | 144,464 (35.98) | 1.132 (1.123–1.140) |
Stroke | 87,896 (64.83) | 47,673 (35.17) | 1.141 (1.128–1.155) |
Chronic kidney disease | 17,263 (63.32) | 10,000 (36.68) | 1.193 (1.163–1.224) |
Cancer | 29,331 (65.73) | 15,295 (34.27) | 1.177 (1.153–1.201) |
Provider type | |||
General hospital | 641,364 (69.37) | 283,228 (30.63) | 0.767 (0.763–0.772) |
Hospital | 216,869 (65.53) | 114,059 (34.47) | 0.964 (0.956–0.971) |
Clinic | 1019,985 (65.35) | 540,715 (34.65) | 1 (ref.) |
Other | 69,578 (67.59) | 33,364 (32.41) | 0.900 (0.888–0.913) |
Year of diagnosis | |||
2011 | 402,660 (64.19) | 224,589 (35.81) | 1 (ref.) |
2012 | 395,541 (66.15) | 202,371 (33.85) | 0.915 (0.909–0.922) |
2013 | 395,450 (68.36) | 183,029 (31.64) | 0.824 (0.818–0.831) |
2014 | 364,782 (67.74) | 173,686 (32.26) | 0.843 (0.837–0.850) |
2015 | 389,363 (67.47) | 187,691 (32.53) | 0.850 (0.843–0.856) |
OR: odds ratio; CI: confidence interval.
Prescription pattern of antihypertensive monotherapy and combination therapy,
Monotherapy | Combination therapy | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ARB | ACEI | BB | CCB | Diuretics | ARB + CCB | Single-pill fixed (ARB + CCB) | ARB + diuretics | Single-pill fixed (ARB + diuretics) | ARB + CCB + diuretics | Separate (ARB + CCB + diuretics) | Others | |
713,667 (24.45) | 44,406 (1.52) | 346,673 (11.88) | 750,337 (25.70) | 92,713 (3.18) | 367,572 (12.59) | 307,781 (83.73) | 285,869 (9.79) | 275,746 (96.46) | 40,691 (1.39) | 38,083 (93.59) | 277,234 (9.50) | |
Age (mean ± SD) | 52.86 ± 12.61 | 50.34 ± 19.56 | 49.32 ± 16.68 | 55.37 ± 13.96 | 52.69 ± 16.7 | 51.96 ± 12.56 | 51.47 ± 12.22 | 53.99 ± 12.52 | 53.84 ± 12.41 | 53.67 ± 13.3 | 53.8 ± 13.28 | 52.68 ± 18.43 |
<20 | 4,492 (9.93) | 4,600 (10.17) | 13,417 (29.67) | 4,786 (10.58) | 2,140 (4.73) | 1,227 (2.71) | 971 (79.14) | 534 (1.18) | 510 (95.51) | 86 (0.19) | 74 (86.05) | 13,940 (30.83) |
20–29 | 15,365 (16.09) | 1,681 (1.76) | 30,155 (31.58) | 18,757 (19.64) | 6,141 (6.43) | 8,426 (8.82) | 7,083 (84.06) | 4,454 (4.66) | 4,279 (96.07) | 830 (0.87) | 747 (90.00) | 9,680 (10.14) |
30–39 | 72,328 (23.83) | 4,051 (1.33) | 48,706 (16.05) | 66,834 (22.02) | 11,075 (3.65) | 43,945 (14.48) | 37,796 (86.01) | 25,751 (8.48) | 24,977 (96.99) | 4,304 (1.42) | 3,981 (92.50) | 26,529 (8.74) |
40–49 | 194,938 (27.32) | 8,606 (1.21) | 75,324 (10.56) | 160,178 (22.45) | 19,047 (2.67) | 109,288 (15.32) | 94,415 (86.39) | 77,024 (10.79) | 74,997 (97.37) | 11,147 (1.56) | 10,387 (93.18) | 57,972 (8.12) |
50–59 | 229,509 (26.49) | 10,949 (1.26) | 87,726 (10.13) | 222,731 (25.71) | 23,283 (2.69) | 114,792 (13.25) | 97,355 (84.81) | 91,574 (10.57) | 88,931 (97.11) | 12,316 (1.42) | 11,522 (93.55) | 73,490 (8.48) |
60–69 | 122,171 (24.02) | 7,423 (1.46) | 52,154 (10.25) | 152,145 (29.91) | 14,918 (2.93) | 54,608 (10.74) | 44,390 (81.29) | 51,040 (10.03) | 49,072 (96.14) | 6,527 (1.28) | 6,157 (94.33) | 47,676 (9.37) |
70–79 | 60,175 (20.41) | 5,136 (1.74) | 30,672 (10.41) | 94,567 (32.08) | 11,552 (3.92) | 26,871 (9.12) | 20,214 (75.23) | 28,025 (9.51) | 26,273 (93.75) | 3,947 (1.34) | 3,749 (94.98) | 33,826 (11.48) |
≥80 | 14,689 (16.04) | 1,960 (2.14) | 8,519 (9.30) | 30,339 (33.12) | 4,557 (4.97) | 8,415 (9.19) | 5,557 (66.04) | 7,467 (8.15) | 6,707 (89.82) | 1,534 (1.67) | 1,466 (95.57) | 14,121 (15.42) |
Sex | ||||||||||||
Male | 420,813 (25.76) | 27,129 (1.66) | 155,995 (9.55) | 417,782 (25.57) | 27,254 (1.67) | 238,220 (14.58) | 200,266 (84.07) | 157,969 (9.67) | 153,329 (97.06) | 25,404 (1.55) | 23,701 (93.30) | 163,202 (9.99) |
Female | 292,854 (22.78) | 17,277 (1.34) | 190,678 (14.83) | 332,555 (25.87) | 65,459 (5.09) | 129,352 (10.06) | 107,515 (83.12) | 127,900 (9.95) | 122,417 (95.71) | 15,287 (1.19) | 14,382 (94.08) | 114,032 (8.87) |
Income | ||||||||||||
Medical aid | 21,158 (18.85) | 1,963 (1.75) | 19,159 (17.07) | 27,747 (24.73) | 5,175 (4.61) | 10,888 (9.70) | 8,507 (78.13) | 8,903 (7.93) | 8,405 (94.41) | 1,477 (1.32) | 1,409 (95.40) | 15,747 (14.03) |
Q1(low) | 179,546 (23.43) | 10,688 (1.39) | 87,246 (11.38) | 196,925 (25.70) | 24,899 (3.25) | 100,997 (13.18) | 84,407 (83.57) | 78,733 (10.27) | 75,970 (96.49) | 12,159 (1.59) | 11,381 (93.60) | 75,185 (9.81) |
Q2 | 167,807 (24.09) | 10,021 (1.44) | 81,121 (11.64) | 176,271 (25.30) | 22,545 (3.24) | 91,692 (13.16) | 77,146 (84.14) | 69,714 (10.01) | 67,372 (96.64) | 10,238 (1.47) | 9,573 (93.50) | 67,234 (9.65) |
Q3 | 166,039 (25.02) | 10,571 (1.59) | 75,841 (11.43) | 171,715 (25.88) | 19,938 (3.00) | 83,991 (12.66) | 70,344 (83.75) | 65,496 (9.87) | 63,175 (96.46) | 9,085 (1.37) | 8,512 (93.69) | 60,848 (9.17) |
Q4 (high) | 179,117 (26.33) | 11,163 (1.64) | 83,306 (12.24) | 177,679 (26.11) | 20,156 (2.96) | 80,004 (11.76) | 67,377 (84.22) | 63,023 (9.26) | 60,824 (96.51) | 7,732 (1.14) | 7,208 (93.22) | 58,220 (8.56) |
Residence | ||||||||||||
Metropolitan | 441,925 (25.38) | 25,693 (1.48) | 208,988 (12.00) | 443,462 (25.47) | 51,973 (2.98) | 222,839 (12.80) | 189,878 (85.21) | 165,196 (9.49) | 159,935 (96.82) | 22,894 (1.31) | 21,283 (92.96) | 158,334 (9.09) |
City | 198,002 (23.75) | 12,818 (1.54) | 100,108 (12.01) | 210,123 (25.20) | 28,099 (3.37) | 106,064 (12.72) | 87,828 (82.81) | 84,793 (10.17) | 81,631 (96.27) | 12,440 (1.49) | 11,738 (94.36) | 81,320 (9.75) |
Rural | 73,740 (21.43) | 5,895 (1.710) | 37,577 (10.92) | 96,752 (28.12) | 12,641 (3.67) | 38,669 (11.24) | 30,075 (77.78) | 35,880 (10.43) | 34,180 (95.26) | 5,357 (1.56) | 5,062 (94.49) | 37,580 (10.92) |
Charlson comorbidity index | ||||||||||||
0 | 223,380 (23.81) | 7,532 (0.80) | 102,265 (10.90) | 259,791 (27.69) | 23,844 (2.54) | 144,663 (15.42) | 126,841 (87.68) | 101,639 (10.83) | 99,032 (97.44) | 14,243 (1.52) | 13,245 (92.99) | 60,777 (6.48) |
1 | 194,677 (24.60) | 9,554 (1.21) | 93,931 (11.87) | 206,751 (26.13) | 26,316 (3.33) | 101,812 (12.86) | 86,629 (85.09) | 81,253 (10.27) | 78,628 (96.77) | 11,177 (1.41) | 10,490 (93.85) | 65,917 (8.33) |
2 | 125,456 (25.22) | 9,257 (1.86) | 61,032 (12.27) | 124,275 (24.98) | 18,034 (3.62) | 55,255 (11.11) | 45,584 (82.50) | 47,316 (9.51) | 45,392 (95.93) | 6,542 (1.31) | 6,118 (93.52) | 50,356 (10.12) |
≥3 | 170,154 (24.58) | 18,063 (2.61) | 89,445 (12.92) | 159,520 (23.05) | 24,519 (3.54) | 65,842 (9.51) | 48,727 (74.01) | 55,661 (8.04) | 52,694 (94.67) | 8,729 (1.26) | 8,230 (94.28) | 100,184 (14.48) |
Comorbidity | ||||||||||||
Diabetes | 146,705 (39.49) | 12,888 (3.47) | 26,869 (7.23) | 65,253 (17.57) | 7,247 (1.95) | 39,243 (10.56) | 31,441 (80.12) | 35,983 (9.69) | 34,825 (96.78) | 4,397 (1.18) | 4,140 (94.16) | 32,892 (8.85) |
Dyslipidemia | 240,239 (29.80) | 17,020 (2.11) | 77,673 (9.63) | 176,764 (21.92) | 16,503 (2.05) | 97,247 (12.06) | 79,833 (82.09) | 78,273 (9.71) | 75,288 (96.19) | 10,327 (1.28) | 9,564 (92.61) | 92,200 (11.44) |
Congestive heart failure | 14,337 (11.87) | 5,768 (4.78) | 26,936 (22.31) | 14,183 (11.75) | 3,867 (3.20) | 6,022 (4.99) | 3,569 (59.27) | 5,859 (4.85) | 4,705 (80.30) | 964 (0.80) | 908 (94.19) | 42,813 (35.46) |
Ischemic heart failure | 58,176 (14.49) | 9,904 (2.47) | 81,919 (20.40) | 99,718 (24.83) | 7,366 (1.83) | 30,283 (7.54) | 19,567 (64.61) | 19,949 (4.97) | 18,447 (92.47) | 4,467 (1.11) | 4,238 (94.87) | 89,765 (22.35) |
Stroke | 31,015 (22.88) | 2,857 (2.11) | 15,783 (11.64) | 34,864 (25.72) | 3,377 (2.49) | 14,745 (10.88) | 9,600 (65.11) | 8,295 (6.12) | 7,727 (93.15) | 2,235 (1.65) | 2,075 (92.84) | 22,398 (16.52) |
Chronic kidney disease | 8,793 (32.25) | 1,102 (4.04) | 1,694 (6.21) | 5,072 (18.60) | 602 (2.21) | 3,088 (11.33) | 1,769 (57.29) | 1,441 (5.29) | 1,297 (90.01) | 344 (1.26) | 324 (94.19) | 5,127 (18.81) |
Cancer | 5,652 (12.67) | 651 (1.46) | 6,097 (13.66) | 16,004 (35.86) | 927 (2.08) | 3,526 (7.90) | 2,498 (70.85) | 2,073 (4.65) | 1,963 (94.69) | 421 (0.94) | 400 (95.01) | 9,275 (20.78) |
Provider type | ||||||||||||
General hospital | 170,474 (18.44) | 27,923 (3.02) | 188,819 (20.42) | 226,705 (24.52) | 27,443 (2.97) | 85,950 (9.30) | 60,437 (70.32) | 25,458 (2.75) | 22,832 (89.68) | 7,785 (0.84) | 6,939 (89.13) | 164,035 (17.74) |
Hospital | 64,955 (19.63) | 3,981 (1.20) | 38,207 (11.55) | 99,156 (29.96) | 10,570 (3.19) | 50,126 (15.15) | 40,075 (79.95) | 26,565 (8.03) | 25,504 (96.01) | 7,847 (2.37) | 7,645 (97.43) | 29,521 (8.92) |
Clinic | 457,721 (29.33) | 10,968 (0.70) | 116,359 (7.46) | 382,965 (24.54) | 51,972 (3.33) | 217,934 (13.96) | 197,185 (90.48) | 223,409 (14.31) | 21,7378 (97.3) | 22,652 (1.45) | 21,151 (93.37) | 76,720 (4.92) |
Others | 20,517 (19.93) | 1,534 (1.49) | 3,288 (3.19) | 41,511 (40.32) | 2,728 (2.65) | 13,562 (13.17) | 10,084 (74.35) | 10,437 (10.14) | 10,032 (96.12) | 2,407 (2.34) | 2,348 (97.55) | 6,958 (6.76) |
Year | ||||||||||||
2011 | 133,122 (21.22) | 11,086 (1.77) | 69,095 (11.02) | 169,958 (27.10) | 19,399 (3.09) | 67,370 (10.74) | 51,975 (77.15) | 74,967 (11.95) | 71,990 (96.03) | 12,913 (2.06) | 12,913 (100) | 69,339 (11.05) |
2012 | 142,023 (23.75) | 10,293 (1.72) | 70,719 (11.83) | 153,033 (25.59) | 19,473 (3.26) | 62,141 (10.39) | 48,491 (78.03) | 69,941 (11.7) | 67,656 (96.73) | 10,217 (1.71) | 10,217 (100) | 60,072 (10.05) |
2013 | 150,777 (26.06) | 9,248 (1.60) | 68,405 (11.82) | 148,626 (25.69) | 18,394 (3.18) | 68,945 (11.92) | 56,772 (82.34) | 55,487 (9.59) | 53,536 (96.48) | 7,025 (1.21) | 6,597 (93.91) | 51,572 (8.92) |
2014 | 136,533 (25.36) | 7,415 (1.38) | 68,083 (12.64) | 134,755 (25.03) | 17,996 (3.34) | 79,351 (14.74) | 70,132 (88.38) | 42,131 (7.82) | 40,626 (96.43) | 5,123 (0.95) | 4,319 (84.31) | 47,081 (8.74) |
2015 | 151,212 (26.20) | 6,364 (1.10) | 70,371 (12.19) | 143,965 (24.95) | 17,451 (3.02) | 89,765 (15.56) | 80,411 (89.58) | 43,343 (7.51) | 41,938 (96.76) | 5,413 (0.94) | 4,037 (74.58) | 49,170 (8.52) |
Prescription pattern by the drug classes, either included in monotherapy or combination therapy,
ARB | ACEI | BETA | CCB | Diuretics | |
---|---|---|---|---|---|
Overall | 150,6561 (51.61) | 90,784 (3.11) | 539,372 (18.48) | 1,314,597 (45.03) | 496,634 (17.01) |
Age (mean ± SD) | 53.01 ± 12.74 | 53.4 ± 17.74 | 51.43 ± 16.17 | 54.32 ± 13.73 | 54.07 ± 13.81 |
<20 | 6,928 (15.32) | 5,564 (12.30) | 15,015 (33.20) | 7,479 (16.54) | 3,092 (6.84) |
20–29 | 31,458 (32.94) | 2,561 (2.68) | 35,064 (36.72) | 32,134 (33.65) | 13,038 (13.65) |
30–39 | 156,422 (51.54) | 7,447 (2.45) | 66,968 (22.06) | 130,704 (43.06) | 48,151 (15.86) |
40–49 | 415,900 (58.29) | 17,660 (2.48) | 118,228 (16.57) | 315,763 (44.25) | 124,418 (17.44) |
50–59 | 476,338 (54.98) | 24,123 (2.78) | 142,677 (16.47) | 393,807 (45.45) | 148,443 (17.13) |
60–69 | 251,389 (49.42) | 17,004 (3.34) | 87,818 (17.26) | 241,238 (47.43) | 86,640 (17.03) |
70–79 | 131,138 (44.49) | 11,737 (3.98) | 55,469 (18.82) | 145,191 (49.26) | 54,624 (18.53) |
≥80 | 36,988 (40.38) | 4,688 (5.12) | 18,133 (19.80) | 48,281 (52.71) | 18,228 (19.90) |
Sex | |||||
Male | 904,778 (55.38) | 60,192 (3.68) | 275,763 (16.88) | 775,090 (47.44) | 251,286 (15.38) |
Female | 601,783 (46.82) | 30,592 (2.38) | 263,609 (20.51) | 539,507 (41.97) | 245,348 (19.09) |
Income | |||||
Medical aid | 46,315 (41.27) | 3,943 (3.51) | 27,160 (24.20) | 46,751 (41.66) | 19,055 (16.98) |
Q1 (low) | 398,887 (52.05) | 22,550 (2.94) | 139,374 (18.19) | 353,498 (46.13) | 138,079 (18.02) |
Q2 | 363,159 (52.13) | 20,640 (2.96) | 126,485 (18.16) | 315,653 (45.31) | 121,217 (17.40) |
Q3 | 346,565 (52.23) | 21,268 (3.21) | 119,086 (17.95) | 299,447 (45.13) | 111,549 (16.81) |
Q4 (high) | 351,635 (51.68) | 22,383 (3.29) | 127,267 (18.7) | 299,248 (43.98) | 106,734 (15.69) |
Residence | |||||
Metropolitan | 909,496 (52.23) | 53,311 (3.06) | 320,725 (18.42) | 778,121 (44.69) | 282,095 (16.20) |
City | 430,908 (51.68) | 25,320 (3.04) | 156,480 (18.77) | 375,042 (44.98) | 148,404 (17.80) |
Rural | 166,157 (48.29) | 12,153 (3.53) | 62,167 (18.07) | 161,434 (46.92) | 66,135 (19.22) |
Charlson comorbidity index | |||||
0 | 502,861 (53.60) | 12,245 (1.31) | 137,490 (14.66) | 456,193 (48.63) | 163,131 (17.39) |
1 | 411,171 (51.96) | 18,536 (2.34) | 136,449 (17.24) | 355,466 (44.92) | 138,614 (17.52) |
2 | 252,680 (50.79) | 19,096 (3.84) | 97,293 (19.56) | 212,683 (42.75) | 85,095 (17.10) |
≥3 | 339,849 (49.10) | 40,907 (5.91) | 168,140 (24.29) | 290,255 (41.94) | 109,794 (15.86) |
Comorbidity | |||||
Diabetes | 240,501 (64.74) | 21,283 (5.73) | 53,265 (14.34) | 127,538 (34.33) | 55,124 (14.84) |
Dyslipidemia | 465,523 (57.74) | 44,577 (5.53) | 155,768 (19.32) | 331,832 (41.16) | 124,074 (15.39) |
Congestive heart failure | 45,540 (37.71) | 22,783 (18.87) | 65,416 (54.18) | 37,246 (30.85) | 16,936 (14.03) |
Ischemic heart failure | 148,348 (36.94) | 40,612 (10.11) | 161,776 (40.29) | 178,876 (44.55) | 44,121 (10.99) |
Stroke | 67,621 (49.88) | 6,568 (4.84) | 34,636 (25.55) | 66,925 (49.37) | 19,360 (14.28) |
Chronic kidney disease | 16,310 (59.82) | 2,274 (8.34) | 5,974 (21.91) | 12,220 (44.82) | 3,257 (11.95) |
Cancer | 13,353 (29.92) | 1,531 (3.43) | 11,312 (25.35) | 24,520 (54.95) | 4,385 (9.83) |
Provider type | |||||
General hospital | 350,910 (37.95) | 67,357 (7.29) | 316,088 (34.19) | 406,074 (43.92) | 81,064 (8.77) |
Hospital | 161,403 (48.77) | 5,958 (1.80) | 57,090 (17.25) | 176,623 (53.37) | 55,586 (16.80) |
Clinic | 946,054 (60.62) | 14,843 (0.95) | 160,542 (10.29) | 668,985 (42.86) | 339,547 (21.76) |
Others | 48,194 (46.82) | 2,626 (2.55) | 5,652 (5.49) | 62,915 (61.12) | 20,437 (19.85) |
Year | |||||
2011 | 312,074 (49.75) | 21,853 (3.48) | 115,374 (18.39) | 291,626 (46.49) | 132,317 (21.09) |
2012 | 306,353 (51.24) | 20,206 (3.38) | 112,748 (18.86) | 257,977 (43.15) | 117,653 (19.68) |
2013 | 300,076 (51.87) | 18,703 (3.23) | 104,476 (18.06) | 252,941 (43.73) | 94,175 (16.28) |
2014 | 280,036 (52.01) | 15,514 (2.88) | 101,408 (18.83) | 245,769 (45.64) | 76,045 (14.12) |
2015 | 308,022 (53.38) | 14,508 (2.51) | 105,366 (18.26) | 266,284 (46.15) | 76,444 (13.25) |
A comparison of prescription rates between 2011 and 2015 revealed an increase of 4% in the prescription rate of ARB and an 8% increase in the rate of thiazide prescription (Figure
Prescription pattern and trend of the antihypertensive drugs. (a) Prescription pattern including combination therapy, (b) trend including combination therapy, (c) prescription number by drug classes, and (d) trend by drug classes.
Among combination therapy users, most patients were prescribed a single-pill fixed-dose combination (83.73% for ARB + CCB and 96.46% for ARB + thiazide, respectively) in an increasing proportion during the study period (Table
Female patients were less likely to be prescribed with combination therapy at first prescription (adjusted odds ratio: 0.764, 95% CI 0.760–0.768). Having congestive heart failure, dyslipidemia, CHD, stroke, CKD, and cancer was slightly associated with initiation with combination therapy, while it was opposite with diabetes mellitus. Primary clinics prescribed combination antihypertensive drugs more frequently than secondary hospitals and general hospitals. Initial combination therapy decreased slightly during the study period (35.81 in year 2011 to 32.53% in year 2015). There was no significant trend by the age group or Charlson comorbidity index (Table
In this study, physicians’ prescription patterns of antihypertensive drugs for treatment-naïve patients were identified using the National Health Insurance claims data. The strength of this study is its generalizability, as it uses claims data collected from the entire South Korean population and assess data over a 5-year period which allows for the identification of trends in prescription patterns.
In a previous study of prescription patterns in Korea conducted in 2009, CCB was the most frequently prescribed antihypertensive (64.4%), followed by diuretics (44.6%), ARB (33.3%), BB (21.6%), and ACEi (11.7%) [
Similarly, we also identified that the use of thiazide diuretics and ACEi was decreasing and ARB use was increasing during the study period. Although CCB was the most frequently prescribed drug for monotherapy, overall ARB was the most frequently prescribed class of antihypertensive drugs since the prescription of ARB for combination therapy also increased.
The prescription of CCBs and ARBs increased worldwide over the past several years [
In some groups, other classes rather than CCBs or ARBs were prescribed frequently. In those less than 20 years of age, the use of ACEi and BBs was more frequent. However, it is unclear why ACEi and BBs were used more frequently than in other age groups. Certain underlying conditions such as diabetes, proteinuria, or migraines as well as physician’s preference considering adverse drug effects may affect the prescription pattern in children and adolescents [
On the contrary, we also observed some gaps between the guidelines and clinical practice. According to the JNC 8 guideline, the use of ARB or ACEi was recommended especially in those with chronic kidney diseases [
Overall, the prescription rate of combination therapy was slightly decreasing throughout the study period. In JNC 8 guideline, patients with stage 2 hypertension (BP > 160/100) are recommended to receive combination therapy from the first prescription [
For initial combination therapy, most patients received single-pill fixed-dose combination drugs and this was an increasing trend. The use of single-pill fixed-dose combination is advantageous in terms of the price of a single-pill combination and the advantage of drug adherence and blood pressure control [
There are several limitations to be considered in this study. First, there is possibility of false claims of hypertension for reimbursement purpose. For example, beta-blockers are often effective in chronic headache but not reimbursed in Korea for that purpose. So, the physician might have entered the hypertension disease code for making the drug covered by the NHI. Second, we do not have detailed clinical information for each prescription and could not determine the appropriateness of drug choice in individual basis.
We identified overall prescription patterns of antihypertensives for treatment-naïve patients in South Korea. The findings can lead to a rational, evidence-based, and cost-effective improvement of prescription patterns in newly diagnosed hypertensive patients.
The data are available at the online public repository of the National Health Insurance Sharing Service (
Kim Y.-H., Jeon S.-A., and Kwon Y.-C. are Pfizer employees. However, they made no influence on this work in relation with the company or its products. Other authors have no potential conflicts of interest to disclose.
The authors would like to thank Ms. Tanaya Bharatan, Pfizer, for her editorial support for this manuscript. This study was sponsored by Pfizer Pharmaceutical Korea Ltd (Grant no. X9001150).