Abstract
BACKGROUND: Angiotensin-converting enzyme inhibitors are effective for many cardiovascular diseases and are widely prescribed, but cough sometimes necessitates their withdrawal.
OBJECTIVE: To develop and validate a model that predicts, by using information available at first prescription, whether a patient will develop cough within 6 months.
DESIGN: Retrospective cohort study with derivation and validation sets.
SETTING: Outpatient clinics affiliated with an urban tertiary care hospital.
PATIENTS: Clinical data were collected from electronic charts. The derivation set included 1,125 patients and the validation set included 567 patients.
INTERVENTIONS: None.
MEASUREMENTS: Angiotensin-converting enzyme inhibitor-induced cough assessed by predetermined criteria.
RESULTS: In the total cohort, 12% of patients developed angiotensin-converting enzyme inhibitor-induced cough. Independent multivariate predictors of cough were older age, female gender, non-African American (with East Asian having highest risk), no history of previous angiotensin-converting enzyme inhibitor use, and history of cough due to another angiotensin-converting enzyme inhibitor. Patients with a history of angiotensin-converting enzyme inhibitor-induced cough were 29 times more likely to develop a cough than those without this history. These factors were used to develop a model stratifying patients into 4 risk groups. In the derivation set, low-risk, average-risk, intermediate-risk, and high-risk groups had a 6%, 9%, 22%, and 55% probability of cough, respectively. In the validation set, 4%, 14%, 20%, and 60% of patients in these 4 groups developed cough, respectively.
CONCLUSIONS: This model may help clinicians predict the likelihood of a particular patient developing cough from an angiotensin-converting enzyme inhibitor at the time of prescribing, and may also assist with subsequent clinical decisions.
Similar content being viewed by others
References
Khalil ME, Basher AW, Brown EJ Jr., Alhaddad IA. A remarkable medical story: benefits of angiotensin-converting enzyme inhibitors in cardiac patients. J Am Coll Cardiol. 2001;37:1757–64.
Halkin A, Keren G. Potential indications for angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease. Am J Med. 2002;112:126–34.
Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2000 Summary. Advance Data from Vital and Health Statistics; No. 328. Hyattsville, Md: National Center for Health Statistics; 2002.
Sebastian JL, McKinney WP, Kaufman J, Young MJ. Angiotensin-converting enzyme inhibitors and cough. Prevalence in an outpatient medical clinic population. Chest. 1991;99:36–9.
Simon SR, Black HR, Moser M, Berland WE. Cough and ACE inhibitors. Arch Intern Med. 1992;152:1698–700.
Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992;117:234–42.
Smyrnios NA, Irwin RS, Curley FJ, French CL. From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults. Arch Intern Med. 1998;158:1222–8.
Gandhi TK, Burstin HR, Cook EF, et al. Drug complications in outpatients. J Gen Intern Med. 2000;15:149–54.
Grossman E, Messerli FH, Neutel JM. Angiotensin II receptor blockers: equal or preferred substitutes for ACE inhibitors? Arch Intern Med. 2000;160:1905–11.
Speirs C, Wagniart F, Poggi L. Perindopril postmarketing surveillance: a 12 month study in 47,351 hypertensive patients. Br J Clin Pharmacol. 1998;46:63–70.
Moore N, Noblet C, Joannides R, Ollagnier M, Imbs JL, Lagier G. Cough and ACE inhibitors. Lancet. 1993;341:61.
Os I, Bratland B, Dahlof B, Gisholt K, Syvertseri JO, Tretli S. Female preponderance for lisinopril-induced cough in hypertension. Am J Hypertens. 1994;7:1012–5.
Elliott WJ. Higher incidence of discontinuation of angiotensin converting enzyme inhibitors due to cough in black subjects. Clin Pharmacol Ther. 1996;60:582–8.
Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators. Am Heart J. 1996;131:350–5.
Woo KS, Norris RM, Nicholls G. Racial difference in incidence of cough with angiotensin-converting enzyme inhibitors (a tale of two cities). Am J Cardiol. 1995;75:967–8.
Ishimitsu T, Yagi S, Ebihara A, et al. Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension. Jpn Heart J. 1997;38:831–40.
Ajayi AA, Adigun AQ. Angioedema and cough in Nigerian patients receiving ACE inhibitors. Br J Clin Pharmacol. 2000;50:81–2.
Malini PL, Strocchi E, Fiumi N, Ambrosioni E, Ciavarella A. ACE inhibitor-induced cough in hypertensive type 2 diabetic patients. Diabetes Care. 1999;22:1586–7.
Lee YJ, Chiang YF, Tsai JC. Severe nonproductive cough and cough-induced stress urinary incontinence in diabetic postmenopausal women treated with ACE inhibitor. Diabetes Care. 2000;23:427–8.
Keane WF, Polis A, Wolf D, Faison E, Shahinfar S. The long-term tolerability of enalapril in hypertensive patients with renal impairment. Nephrol Dial Transplant. 1997;12(suppl 2):75–81.
Gilchrist NL, Richards AM, March R, Nicholls MG. Effect of sulindac on angiotensin converting enzyme inhibitor-induced cough: randomised placebo-controlled double-blind cross-over study. J Hum Hypertens. 1989;3:451–5.
Fogari R, Zoppi A, Tettamanti F, Malamani GD, Tinelli C, Salvetti A. Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study. J Cardiovasc Pharmacol. 1992;19:670–3.
Tenenbaum A, Grossman E, Shemesh J, Fisman EZ, Nosrati I, Motro M. Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough. Am J Hypertens. 2000;13:776–82.
Knox AJ, Pang L. Tackling ACE inhibitor cough. Lancet. 1997;350:814.
Tu JV, Naylor CD. Clinical prediction rules. J Clin Epidemiol. 1997;50:743–4.
Metz CE. Basic principles of ROC analysis. Semin Nucl Med. 1978;8:283–98.
Laupacis A, Sekar N, Stiell IG. Clinical prediction rules. A review and suggested modifications of methodological standards. JAMA. 1997;277:488–94.
Bates DW, Lee TH. Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA. 1992;267:1962–6.
Bates DW, Leape LL, Cullen DJ, et al. Effect of computerized physician order entry and a team intervention on prevention of serious medication errors. JAMA. 1998;280:1311–6.
Raschke RA, Gollihare B, Wunderlich TA, et al. A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital. JAMA. 1998;280:1317–20.
Wang SJ, Kuperman GJ, Ohno-Machado L, Onderdonk A, Sandige H, Bates DW. Using electronic data to predict the probability of true bacteremia from positive blood cultures. Proc AMIA Symp. 2000:893–7.
Goldman L, Cook EF, Brand DA, et al. A computer protocol to predict myocardial infarction in emergency department patients with chest pain. N Engl J Med. 1988;318:797–803.
Goldman L, Cook EF, Johnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to the emergency departments with acute chest pain. N Engl J Med. 1996;334:1498–504.
Bates DW, Ebell M, Gotlieb E, Zapp J, Mullins HC. A proposal for electronic medical records in U.S. primary care. J Am Med Inform Assoc. 2003;10:1–10.
Randolph AG, Guyatt GH, Calvin JE, Doig G, Richardson WS. Understanding articles describing clinical prediction tools. Evidence Based Medicine in Critical Care Group. Crit Care Med. 1998;26:1603–12.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported in part by grants from the Pfizer Health Research Foundation and the Health Care Science Institute and grant R01-HS11169 from the Agency for Healthcare Research and Quality.
Dr. Morimoto received fellowship grant support from the St. Luke’s Life Science Institute, Tokyo.
Rights and permissions
About this article
Cite this article
Morimoto, T., Gandhi, T.K., Fiskio, J.M. et al. Development and validation of a Clinical prediction rule for angiotensin-converting enzyme inhibitor-induced cough. J GEN INTERN MED 19, 684–691 (2004). https://doi.org/10.1111/j.1525-1497.2004.30016.x
Issue Date:
DOI: https://doi.org/10.1111/j.1525-1497.2004.30016.x