TY - JOUR
T1 - Association of 3 different antihypertensive medications with hip and pelvic fracture risk in older adults secondary analysis of a randomized clinical trial
AU - Puttnam, Rachel
AU - Davis, Barry R.
AU - Pressel, Sara L.
AU - Whelton, Paul K.
AU - Cushman, William C.
AU - Louis, Gail T.
AU - Margolis, Karen L.
AU - Oparil, Suzanne
AU - Williamson, Jeffrey
AU - Ghosh, Alokananda
AU - Einhorn, Paula T.
AU - Barzilay, Joshua I.
AU - Furberg, Curt D.
AU - Wright, Jackson T.
AU - Cutler, Jeffrey A.
AU - Alderman, Michael
AU - Black, Henry
AU - Grimm, Richard
AU - Haywood, L. Julian
AU - Leenen, Frans
AU - Probstfield, Jeffrey
AU - Nwachuku, Chuke
AU - Gordon, David
AU - Proschan, Michael
AU - Ford, Charles E.
AU - Piller, Linda B.
AU - Dunn, Kay
AU - Goff, David
AU - Bettencourt, Judy
AU - DeLeon, Barbara
AU - Simpson, Lara M.
AU - Blanton, Joe
AU - Geraci, Therese
AU - Walsh, Sandra M.
AU - Nelson, Christine
AU - Rahman, Mahboob
AU - Juratovac, Anne
AU - Pospisil, Robert
AU - Carroll, Lillian
AU - Sullivan, Sheila
AU - Russo, Jeanne
AU - Barone, Gail
AU - Christian, Rudy
AU - Feldman, Sharon
AU - Lucente, Tracy
AU - Calhoun, David
AU - Jenkins, Kim
AU - McDowell, Peggy
AU - Eckfeldt, J.
AU - Lopez, F.
AU - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group
PY - 2017/1/1
Y1 - 2017/1/1
N2 - IMPORTANCE On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. OBJECTIVE To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. DESIGN, SETTING, AND PARTICIPANTS Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. MAIN OUTCOMES AND MEASURES Hip and pelvic fracture hospitalizations. RESULTS A total of 22 180 participants (mean [SD] age, 70.4 [6.7] years; 43.0%female; and 49.9%white non-Hispanic, 31.2%African American, and 19.1%other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79; 95%CI, 0.63-0.98; P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75; 95%CI, 0.58-0.98; P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82; 95%CI, 0.63-1.08; P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95%CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. CONCLUSIONS AND RELEVANCE These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications.
AB - IMPORTANCE On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. OBJECTIVE To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. DESIGN, SETTING, AND PARTICIPANTS Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. MAIN OUTCOMES AND MEASURES Hip and pelvic fracture hospitalizations. RESULTS A total of 22 180 participants (mean [SD] age, 70.4 [6.7] years; 43.0%female; and 49.9%white non-Hispanic, 31.2%African American, and 19.1%other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79; 95%CI, 0.63-0.98; P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75; 95%CI, 0.58-0.98; P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82; 95%CI, 0.63-1.08; P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95%CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. CONCLUSIONS AND RELEVANCE These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications.
UR - http://www.scopus.com/inward/record.url?scp=85011294803&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011294803&partnerID=8YFLogxK
U2 - 10.1001/jamainternmed.2016.6821
DO - 10.1001/jamainternmed.2016.6821
M3 - Article
C2 - 27893045
AN - SCOPUS:85011294803
SN - 2168-6106
VL - 177
SP - 67
EP - 76
JO - JAMA internal medicine
JF - JAMA internal medicine
IS - 1
ER -