ORIGINAL INVESTIGATION Calcium Channel Blockers and Mortality in Elderly Patients With Myocardial Infarction James G. Jollis, MD; Ross J. Simpson, Jr, MD, PhD; Mridul K. Chowdhury, PhD; Wayne E. Cascio, MD; John R. Crouse III, MD; Mark W. Massing, MD, MPH; Sidney C. Smith, Jr, MD Background: Although calcium channel blockers are Results: Calcium channel blockers were widely pre- a useful therapy in relieving angina, lowering blood pres- scribed at hospital discharge to elderly patients with sure, and slowing conduction of atrial fibrillation, grow- myocardial infarction between 1994 and 1995 ing evidence has cast doubt on their safety in patients with (n = 51 921), the most commonly prescribed being dil- coronary disease. tiazem (n = 21 175), nifedipine (n = 12 670), amlo- dipine (n = 11 683), and verapamil (n = 3639). After Objective: To examine the association between cal- adjusting for illness severity and concomitant medica- cium channel blocker therapy at hospital discharge and tion use, patients who were prescribed calcium chan- mortality in a population-based sample of elderly pa- nel blockers at hospital discharge did not have tients hospitalized with acute myocardial infarction. increased risk for 30-day or 1-year mortality, with the exception of the few (n = 116) treated with bepridil. Design: Retrospective cohort study using data from medi- Bepridil differs from other calcium channel blockers cal charts and administrative files. because of its tendency to prolong repolarization, and its association with proarrhythmic effects in elderly Setting: All acute care hospitals in 46 states. patients. Patients: All Medicare patients with a principal diag- Conclusion: We did not identify a mortality risk in a nosis of acute myocardial infarction consecutively dis- large consecutive sample of elderly patients with myo- charged from the hospital alive during 8-month periods cardial infarction, which supports the need for addi- between 1994 and 1995 (N = 141 041). tional prospective trials examining calcium channel blocker therapy for ischemic heart disease. Main Outcome Measure: Mortality at 30 days and 1 year. Arch Intern Med. 1999;159:2341-2348 ALCIUM CHANNEL block- nel blocker therapy, and further studies in- ers represent a poten- volving large numbers of patients are tially useful therapy for needed to examine the safety of their use. elderly patients with coro- Given current apprehension among clini- nary artery disease, given cians regarding calcium channel blocker theirC ability to relieve angina, lower blood therapy, such studies are unlikely to be From the Duke Clinical pressure, and slow conduction of atrial fi- performed, particularly involving formu- Research Institute, Duke brillation. However, growing evidence has lations for which patents have expired. University, Durham, NC cast doubt on their safety. In post hoc Decisions regarding the use of calcium (Dr Jollis); Medical Review of analyses, the Multicenter Diltiazem Postin- channel blockers in the elderly are even North Carolina Inc, Cary farction Trial (MDPIT)1 found higher rates more difficult, given the relatively few (Drs Simpson and Chowdhury); of nonfatal reinfarction or cardiac death elderly patients enrolled in previous tri- Division of Cardiology associated with diltiazem treatment in pa- als. In 1995, calcium channel blockers— (Drs Simpson, Cascio, and tients with myocardial infarction (MI) and including nifedipine, diltiazem, and ver- Smith) and Department of pulmonary congestion or reduced ejec- apamil—were widely used among Epidemiology (Dr Massing), tion fraction. More recently, a meta- Medicare patients. We examined the re- University of North Carolina, 2 Chapel Hill; and the analysis of nifedipine therapy after acute lationship between calcium channel Department of Medicine, Wake MI identified higher mortality associated blocker use after acute MI and survival for Forest University School of with nifedipine therapy on a dose-re- 141 041 elderly patients, as part of the Medicine, Winston-Salem, NC sponse basis. These findings have led to Health Care Financing Administration’s (Dr Crouse). much uncertainty regarding calcium chan- Cooperative Cardiovascular Project (CCP). ARCH INTERN MED/ VOL 159, OCT 25, 1999 WWW.ARCHINTERNMED.COM 2341 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Table 1. Thirty-Day Mortality Logistic Regression Model* PATIENTS AND METHODS Variable Odds Variable Estimate x2 P . Ratio PATIENT POPULATION Intercept −3.57 727.79 .001 The CCP abstracted hospital charts of Medicare patients Age from 65 y 0.04 51.39 .001 1.04 Age from 65 y squared −0.0003 1.87 .17 1.00 withaprincipaldiagnosisofacuteMI(InternationalClas- Female −0.15 29.48 .001 0.86 sification of Diseases codes 410.x0 and 410.x1) consecu- Black −0.12 4.29 .04 0.89 tively discharged from the hospital during 8-month pe- Anterior infarction 0.18 38.56 .001 1.20 3-5 riods between 1994 and 1995, in 46 states. Informa- Inferior infarction −0.01 0.25 .62 0.99 tion collected for each Medicare patient included patient Non–Q wave infarction −0.19 45.80 .001 0.82 identifiers, hospitalization dates, demographics, chest Systolic blood pressure −0.007 263.17 .001 0.99 pain history, physical examination findings, medica- Pulse 0.003 31.62 .001 1.00 tions used, presence or absence of contraindications to Respiratory rate 0.01 23.06 .001 1.01 therapy,electrocardiograms,cardiacenzymelevels,treat- Rales or pulmonary congestion 0.15 26.23 .001 1.16 ment, complications, and survival status. Accuracy of Ejection fraction 40%-59% −0.53 206.58 .001 0.59 hospital chart abstraction was evaluated on a monthly Ejection fraction .60% −0.97 177.00 .001 0.38 basis by masked reabstraction, with agreement rates by Ejection fraction missing −0.14 16.32 .001 0.87 data element in the 85% to 95% range. Calcium chan- Previous myocardial infarction 0.03 1.30 .25 1.03 nel blockers were identified at 2 points in the CCP chart Previous congestive heart failure 0.08 6.82 .009 1.08 abstraction, according to discharge medications entered Previous bypass surgery 0.06 2.19 .14 1.06 by free text and by a specific variable for “calcium chan- Previous angioplasty −0.37 33.45 .001 0.69 Electrocardiogram—atrial 0.15 25.50 .001 1.16 nel blocker at discharge.” These 2 variables agreed for fibrillation 51 843 of 51 921 patients we identified as being treated Electrocardiogram—heart block 0.10 2.59 .11 1.11 with calcium channel blockers, and for 89 099 of 89 120 Electrocardiogram—myocardial 0.11 10.25 .001 1.12 patientsnotbeingtreated.Allpatientsolderthan65years infarction who were discharged from the hospital alive were in- Diabetes 0.13 20.32 .001 1.14 cludedinthepresentstudy.Datesofdeathwereobtained Hypertension −0.16 29.31 .001 0.86 from the Medicare Enrollment Database and the Social Previous stroke 0.06 2.96 .08 1.06 SecurityAdministration’sMasterBeneficiaryRecordFile. Peripheral vascular disease 0.10 7.62 .006 1.11 Obstructive pulmonary disease 0.08 5.57 .018 1.08 DATA ANALYSIS Current cigarette smoker 0.18 18.58 .001 1.20 Dementia 0.39 98.80 .001 1.48 The primary analysis of the present study compared Serum urea nitrogen level, ,5 −0.13 7.25 .007 0.88 the mortality of patients who were prescribed cal- mmol/L Serum urea nitrogen level, 7-8 0.19 19.05 .001 1.21 cium channel blockers at hospital discharge after acute mmol/L MI with that of patients discharged but not taking Serum urea nitrogen level, 9-10 0.24 24.63 .001 1.27 these drugs. Calcium channel blockers were classi- mmol/L fied as nifedipine, amlodipine, other dihydropteri- Serum urea nitrogen level, ,10 0.60 234.58 .001 1.82 dines, diltiazem, verapamil, and bepridil hydrochlo- mmol/L ride. Baseline characteristics and outcomes were Serum urea nitrogen level 0.17 5.15 .023 1.19 compared between treatment categories using x2 tests missing for categorical variables and analysis of variance for Walks with assistance 0.30 90.61 .001 1.35 continuous variables. Unable to walk 1.22 715.83 .001 3.39 Thirty-day and 1-year mortality after hospital dis- Unable to determine mobility 0.88 92.84 .001 2.41 charge were examined in logistic regression models Congestive heart failure 0.56 304.32 .001 1.74 after adjusting for illness severity, medications taken, Recurrent angina 0.23 64.10 .001 1.26 and propensity for treatment with calcium channel Shock 0.17 6.65 .01 1.19 blockers (propensity score). Logistic model vari- Reinfarction 0.24 11.49 .001 1.28 Stroke 0.55 93.28 .001 1.73 ables were selected on the basis of their association Hemorrhage −0.008 0.05 .82 0.99 with mortality according to previous work, strength Cardiac arrest 0.13 4.66 .03 1.14 of association, and clinical intuition (Table 1 and Discharged to nonacute hospital 0.74 448.40 .001 2.10 Table 2). Specific model components included age, Discharged to home health care 0.27 50.16 .001 1.30 sex, race, descriptors of MI and coronary disease se- Propensity decile 1 −0.73 68.36 .001 0.48 verity, comorbid illnesses, mobility at discharge, dis- Propensity decile 2 −0.48 35.28 .001 0.62 charge destination, and propensity score. Propen- Propensity decile 3 −0.27 12.42 .001 0.76 sity score was derived according to the methods of Propensity decile 4 −0.23 9.44 .002 0.79 Rubin6 using an additional logistic model to exam- Propensity decile 5 −0.19 6.87 .009 0.82 ine characteristics associated with being discharged Propensity decile 6 −0.22 9.29 .002 0.80 while taking a calcium channel blocker.7 Compo- Propensity decile 7 −0.14 3.97 .05 0.87 nent variables for the propensity model were se- Propensity decile 8 −0.10 1.89 .17 0.91 lected in a similar manner as those for the mortality Propensity decile 9 −0.05 0.56 .46 0.95 models, using association with calcium channel Discharged while taking calcium −0.04 2.20 .14 0.96 blocker therapy as the gauge of importance (Table 3).