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Prevalence of concurrent prescribing of ACE-Is and ARBs among beneficiaries of Puerto Rico's government-sponsored health care plan during 2012 and 2013.

Cardiovascular diseases are the second leading cause of death in Puerto Rico (1). Current recommendations for the treatment of cardiovascular diseases include the use of medications with proven benefits in reducing morbidity and mortality. Because of their proven clinical benefits, drugs that act on the renin-angiotensin system (RAS) such as angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) have become the first-line therapy for many patients with cardiovascular conditions. RAS plays an important role in the regulation of blood pressure, plasma volume, and sympathetic nervous system activity to maintain organ perfusion (2). Pharmacotherapy with ACE-Is or ARBs has been shown to reduce morbidity and mortality among patients with hypertension (HTN), heart failure (HF), or post-myocardial infarction (MI) and to halt the progression of chronic kidney disease (2, 3).

ACE-Is inhibit the enzymatic conversion of angiotensin I to angiotensin II, which inhibition causes an initial reduction in AT-II levels. With the chronic use of ACE-Is, the levels of AT-II gradually increase to pretreatment values (4). This is caused by the production of AT-II by non-ACE pathways. This phenomenon, termed ACE escape, has led many scientists to believe that combining ACE-Is with ARBs to more completely block RAS would translate into better cardiovascular outcomes. Dual RAS blockage with ACE-Is and ARBs became a common medical practice despite the lack of evidence in cardiovascular end points (2-5). The benefits of dual RAS blockage have been documented for several CV and renal diseases, such as HTN, HF, post-MI LVD (left ventricle dystrophy), and chronic kidney disease with proteinuria.

Initial studies that evaluated the effects of the combination therapy in the treatment of HTN showed that this therapy had a modest additive effect on blood pressure, but the effects on cardiovascular outcomes were not evaluated (6-9). Some of the most compelling evidence of the effects of dual therapy in cardiovascular outcomes comes from the ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial) (10). In the ONTARGET study (the endpoint of which is a composite of CV death, MI, stroke or hospitalization for HF), no additional cardiovascular benefit was observed when combining an ACE-I and an ARB compared to when ACE-I monotherapy was implemented. A statistically significant increase in the incidence of renal failure, hyperkalemia, and hypotension was observed in the combination group, along with only a moderate decrease in blood pressure.

A study reported that dual RAS blockage decreases proteinuria to a greater extent than ACE-I monotherapy does. However, this decrease in proteinuria didn't translate into a decrease in the progression to end-stage renal disease and dialysis. Therefore, the decrease in the surrogate endpoint didn't translate into better cardiovascular and renal outcomes (2). The VA-NEPHRON-D study, a large-scale clinical trial evaluating the effect of dual RAS blockades in patients with diabetic nephropathy, had to be stopped early because of a high incidence of acute kidney injury and hyperkalemia and no additional benefit in the combination group (11). The lack of clinical benefit of the dual therapy has also been proven in nephropathy not related to DM. The HALT-PKD trials failed to demonstrate the clinical superiority of dual therapy compared to ACE-I monotherapy among patients with hypertensive ADPKD (autosomal dominant polycystic kidney disease) (12-14).

Although both ACE-Is and ARBs have demonstrated benefits as monotherapies in preventing cardiac remodeling after myocardial infarction, their combination hasn't proved to provide such benefits (15). The Valsartan in Acute Myocardial Infarction Trial (VALIANT) evaluated the efficacy and safety of the ACE-I and ARB combination in patients with post-MI LVD. In this study, combination therapy didn't improve survival over monotherapy with either an ACE-I or an ARB, and discontinuation rates associated with adverse events such as hyperkalemia and renal dysfunction were higher in the dual-therapy group (16).

Due to the lack of benefits and increased risks associated with the concurrent therapy composed of an ACE-I and an ARB, this approach cannot be recommended for any CV-related condition at present, with the exception of HF, and that in only select patients.

According to ACCF/AHA treatment guidelines published in 2013, combining an ACE-I and an ARB may be an alternative for patients with reduced ejection fraction and classified as AHA (American Heart Association) stage C or stage D who remain symptomatic after an adequate dose of an ACE-I and a beta-blocker (unless contraindicated) and who cannot tolerate an aldosterone receptor antagonist or in whom such an antagonist is contraindicated (17). The more recently published European guidelines also addressed the combination of ACE-Is and ARBs in the treatment of HF. According to the guidelines, the combination of ACE-Is and ARBs should be used under strict medical supervision and restricted to patients with reduced ejection fraction who remain symptomatic with a beta-blocker and who are unable to tolerate a mineralocorticoid receptor antagonist (18, 19). Although the combination has not consistently proved to decrease mortality in such patients, a decrease in hospitalizations due to HF has been reported in some clinical trials (18, 20).

The purpose of this study was to estimate the prevalence of the concurrent prescribing of ACE-Is and ARBs, alone or as a combination product, among beneficiaries of the Puerto Rico Health Insurance Administration during the years of 2012 and 2013. Although major pertinent clinical guidelines for the treatment of heart failure and hypertension were published after this study was conducted (17, 21), compelling evidence of the potential risks of the combination was published since the large scale ONTARGET trial in 2008 (10). Clinicians should be aware of the impact of evidence-based medicine and should not rely solely on published treatment guidelines, as they may not always reflect the most recent research findings.

Methods

This 2-year study followed a cross-sectional design. All pharmacy claims during the years 2012 and 2013 involving an ACE-I, an ARB, or a combination product containing either of these 2 therapeutic classes of drugs were provided by ASES. Each pharmacy claim number was complemented with the following variables: 1) a unique scrambled identifier for the beneficiary who generated the claim; 2) the year and month the claim was generated; 3) the name of the drug product associated with the claim; 4) the National Drug Code of the drug product associated with the claim; 5) the major drug classification of the drug product associated with the claim; and 6) the therapeutic class of the drug product associated with the claim. The resulting dataset was named pharmacy claims dataset and was sorted by the beneficiary number and the year and month in which each claim was generated. The months of January to December 2012 were numbered from 1 to 12, and the months of January to December 2013 were numbered from 13 to 24. Each of the 24 periods was analyzed for each beneficiary to find duplicate therapies and, thereby, identify the most prevalent combinations of such therapies. Duplicate therapy was defined as having more than 1 pharmacy claim for an ACE-I, an ARB, a combination product, or any combination of these 3 groups in a single month for at least 2 consecutive months. The 2-consecutive-months rule was used to minimize the probability of capturing transitions from one therapy to another, instead of real duplicate therapies. The prevalence of the occurrence of at least 2 concurrent claims for an ACE-I, an ARB, and/or a combination product for the same beneficiary during 2 consecutive months was calculated.

A second dataset was provided by ASES. This dataset contained information on sociodemographics and primary diagnoses for the beneficiaries in the pharmacy claims dataset. The main purpose of creating this dataset was to be able to identify beneficiaries in the pharmacy claims dataset where the duplicate therapy was possibly indicated, which beneficiaries would be, for example, those who had suffered from heart failure. The resulting data repository was named the sociodemographics and primary diagnosis dataset. This data was merged with the pharmacy claims dataset by the unique beneficiary identification number. Beneficiaries whose data were not present in both datasets were excluded from the analysis, stratifying by primary diagnosis. The final dataset was analyzed at the person-month level using frequency, cumulative frequency, percentage, and cumulative percentage. This research was submitted to and approved by the University of Puerto Rico Medical Sciences Campus Institutional Review Board.

Results

The pharmacy claims dataset contained a total of4,042,823 claims for ACE-Is, ARBs, or combination products containing any of the drugs in these 2 therapeutic classes, which claims were generated by 361,841 unique beneficiaries (Table 1). After sorting by the beneficiary number and by the year and month in which each claim was generated, a total of 150,264 (3.72%) pharmacy claims generated by 37,120 (10.26%) beneficiaries were associated with 2 or more prescriptions (per month) for ACE-Is, ARBs, or combination products for the same beneficiary for 2 consecutive months. This prevalence does not exclude cases in which duplicate therapy may be indicated, such as those cases in which the beneficiary was diagnosed with heart failure. To capture cases where duplicate therapy may be indicated, a secondary analysis was conducted in which the pharmacy claims were merged with sociodemographic and primary diagnosis information.

In the sociodemographics and primary diagnosis claims dataset, a total of 23,598 (6.5%) beneficiaries without primary diagnosis information were excluded, leaving a final pool of 338,243 beneficiaries with at least 1 pharmacy claim for an ACE-I, an ARB, or a combination product containing any of the drugs in either of these 2 therapeutic classes (Table 2). The mean age of these beneficiaries was 61 years, and more than half were female (58.51%). A total of 36,202 (10.7%) beneficiaries had 2 or more claims for an ACE-I, an ARB, or combination products in a single month, for 2 consecutive months.

The most prevalent duplicate therapy combination consisted of ACE-Is and ARBs (49.3%), followed by ACE-Is or ARBs and a combination product (21.3% and 13.9%, respectively) (Table 3). Combinations of 2 ACE-Is or 2 ARBs, rare duplicate combinations, and multiple (>2) drug therapy combinations were also observed. The highest prevalence of duplicate therapy was observed in the western and eastern regions of the ASES coverage area, and the primary diagnoses most commonly associated with these claims were diabetes mellitus and hypertension. A primary diagnosis of HF was identified in 1,124 (3.10%) of the beneficiaries (Table 3). Excluding these beneficiaries, a total of35,078 beneficiaries were co-prescribed any combination of ACE-Is and ARBs during 2012 and 2013 for a primary diagnosis other than heart failure. They represented 10.4% of all the beneficiaries who were prescribed at least 1 ACE-I, 1 ARB, or a combination product during the study period (Table 4).

Discussion

ACE-I and ARB pharmacotherapies are frequently prescribed to beneficiaries of Puerto Rico's government-sponsored health care plan. This study identified more than 4 million pharmacy claims (made within the 2-year study period) for these pharmacological products. Interestingly, 10.26% of all the beneficiaries who received at least 1 ACE-I, ARB, or combination product, were receiving a dual RAS blockade with ACE-Is, ARBs, or combination products.

To the best of our knowledge, this is the first study to measure the prevalence of the concurrent prescribing of ACE-Is and ARBs in the United States. A similar study evaluated the trends of the co-prescription of ACE-Is and ARBs in Ireland from 2000 to 2009 (20). The authors reported that 0.3% of the Irish population were receiving a dual RAS blockade over the study period. The Irish study had a population distribution and a prevalence of cardiovascular disease similar to those reported in this study. However, their study was performed over a longer period of time (9 years) and during years in which conflictive evidence of the combination was being published. Although a higher concurrent prescribing of dual RAS blockade therapies was to be expected in the Irish study, the study described herein revealed a higher prevalence in a more recent and shorter time frame.

The concurrent prescribing of ACE-Is and ARBs for 2 consecutive months was present in a range of 2 to 8 claims per patient-month, with the majority of beneficiaries being on duplicate therapy. Having 2 or more claims could be explained by the following: It is possible that the prescribers believed that an additional benefit would accrue from using the combination; there may have been different prescribers for the same patient; there may have been a lack of communication between a given patient and his or her healthcare professionals (including doctors and pharmacists) and/or between those professionals assisting that patient. Another possibility that must be considered is that such dual prescribing might have been caused by the flaws in the current health care plan and the system that regulates it. The concurrent prescribing of more than 3 dual RAS blockade therapies represented less than 1% of the final dataset.

After evaluating each beneficiary's sociodemographic information and primary diagnosis, and excluding those beneficiaries with incomplete information, it was found that a total of 10.7% of the remaining beneficiaries had 2 or more concurrent pharmacy claims for dual RAS blockade in a single month, for 2 consecutive months. The most prevalent combination was at least 1 ACE-I together with at least 1 ARB.

Although a dual RAS blockade was initially thought to be useful in many CV and renal conditions, the current clinical literature recommends its use only in select patients with HF (17). In this study, the primary diagnoses associated with dual RAS blockage were hypertension and diabetes, which are also the main comorbidities in the Puerto Rican population (22). Only 3.10% of the beneficiaries with concurrent dual RAS blockade therapies had a primary diagnosis of HF, which means that 10.4% of the beneficiaries were prescribed a combination therapy without there being a diagnostic indication (per current treatment guidelines) of its necessity. It is important to note that in both the 2012 and 2013 ADA (American Diabetes Association) treatment guidelines, a regimen that includes an ACE-I or an ARB was recommended as the first-line treatment for patients with hypertension and diabetes. Those guidelines do not directly assess combination therapy, but instead recommend using one class of drug or the other (23, 24). Similarly, the guidelines for hypertension in the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), which were published in 2003 and updated in 2013, didn't directly address the combination of an ACE-I and an ARB for the treatment of hypertension, either alone or with any other compelling indications (25).

Pertinent clinical guidelines that explicitly addressed the combination of ACE-Is and ARBs (e.g., the ACC/AHA HF guidelines and the eighth Joint National Committee [JNC-8] hypertension guidelines) were updated in late 2013, at the end of our study period. Although the fact that the updated guidelines were released late in the "life" of our study may be seen as a potential limitation, it really emphasizes the importance of incorporating updated research clinical evidence into the medical practice. Clinical research is published constantly, and some of the findings of important clinical research end up changing the way medicine is practiced. Clinicians should keep reading medical literature in order to provide patients with the most recent and validated treatment recommendations. Treatment guidelines are only guidelines, and sometimes it takes time to update recommendations based on recent evidence. Ultimately, clinicians are responsible for their patients' clinical outcomes, no matter what the guidelines recommend--especially if outdated guidelines are used to make important clinical decisions.

One limitation of this study was that the database did not provide information about HF stage, making it impossible to determine whether there was really a possible indication for concomitant prescribing in these beneficiaries. Moreover, we could identify only the primary diagnosis of each of the beneficiaries. Other possible comorbidities not listed as primary, which may also include HF, couldn't be identified. This may have caused an overestimation of inappropriate co-prescribing in this study. Another limitation of this study was that the database is representative of only the medically indigent and elderly population enrolled in the government health care plan. In addition, the study was performed during a 2-year time frame, which makes it difficult to determine whether there has been an increasing or decreasing trend of concurrent prescribing.

Conclusion

To our knowledge this is the first study that reports the prevalence of the concurrent prescribing of ACE-Is and ARBs in the Puerto Rican population. An unacceptable pattern of ACE-I and ARB co-prescribing was observed among beneficiaries with diagnoses for which the combination is not supported by clinical evidence or current treatment guidelines. There is a need to develop education policies and strategies aimed at prescribers and health plans to ensure the safe and effective use of these pharmacotherapies. Such strategies could lead to reducing the concurrent prescribing of RAS blockade therapies and subsequently decreasing health care costs, and lead, as well, to the elimination of those risks associated with concurrent prescribing, which risks include hyperkalemia, hypotension, and acute renal failure. As a result, the successful implementation of these kinds of programs may further contribute to the reduction of morbidity and mortality associated with poor management in the treatment of cardiovascular diseases.

Acknowledgments

The authors wish to thank collaborators David Santiago, Planning and Quality Affairs Division Evaluation Analyst, and Isabel Hernandez Lopez for their efforts in acquiring the data needed for our analysis from the government-sponsored health care plan.

References

(1.) Armendariz AR, Sanchez-Hernandez EM, Rosado-Santiago NM, et al. Informe de la Salud en Puerto Rico, 2014. San Juan, PR: Departament de Salud; 2014:1-211.

(2.) Krause MW, Fonseca VA, Shah SV. Combination Inhibition of the Renin-Angiotensin System: Is More Better? Kidney Int. 2011,-80: 245-255.

(3.) Wong J. Is There Benefit in Dual Renin-Angiotensin-Aldosterone System Blockade? No, Yes and Maybe: A Guide for the Perplexed. Diab Vasc Dis Res 2013, 10:193-201.

(4.) Holdiness A, Monahan K, Minor D, De Shazo RD. Renin Angiotensin Aldosterone System Blockade: Little to No-Rationale for ACE-I and ARB Combinations. Am J Med 2011, 124:15-19.

(5.) Mallat SG. Dual Renin-Angiotensin System Inhibition for Prevention of Renal and Cardiovascular Events: Do the Latest Trials Challenge Existing Evidence? Cardiovasc Diabetol 2013, 12:108.

(6.) Azizi M, Linhart A, Alexander J, et al. Pilot Study of Combined Blockade of the Renin-Angiotensin System in Essential Hypertensive Patients. J Hypertension 2000, 18:1139-1147.

(7.) Izzo JL, Weinberg MS, Hainer JW, Kerkering J, Tou CK, AMAZE. Antihypertensive Efficacy of Candesartan-Lisinopril in Combination Vs. Up-Titration of Lisinopril: The AMAZE Trials. J Clin Hypertens (Greenwich). 2004, 6:485-493.

(8.) Mogensen CE, Neldam S, Tikkanen I, et al. Randomised Controlled Trial of Dual Blockade of Renin-Angiotensin System in Patients with Hypertension, Microalbuminuria, and Non-Insulin Dependent Diabetes: The Candesartan and Lisinopril Microalbuminuria (CALM) Study. BMJ 2000,321:1440-1444.

(9.) Stergiou GS, Skeva II, Baibas NM, et al. Additive Hypotensive Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Antagonism in Essential Hypertension. J Cardiovasc Pharmacol. 2000,35:937-941.

(10.) ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, et al. Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events. N Engl J Med 2008, 358:1547-1559.

(11.) Fried LF, Duckworth W, Zhang JH, et al., VA NEPHRON-D Investigators. Design of Combination Angiotensin Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (Va Nephron-D). Clin J Am Soc Nephrol. 2009, 4: 361-368.

(12.) Chapman AB, Torres VE, Perrone RD, et al. The HALT Polycystic Kidney Disease Trials: Design and Implementation. Clin J Am Soc Nephrol 2010, 5:102-109.

(13.) Schrier RW, Abebe KZ, Perrone RD, et al., HALT-PKD Trial Investigators. Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease. N Engl J Med 2014, 371:2255-2266.

(14.) Torres VE, Abebe KZ, Chapman AB, et al., HALT-PKD Trial Investigators. Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease. N Engl J Med 2014, 371:2267-2276.

(15.) Nakamura Y, Yoshiyama M, Omura T, et al. Beneficial Effects of Combination of Ace Inhibitor and Angiotensin II Type 1 Receptor Blocker on Cardiac Remodeling in Rat Myocardial Infarction. Cardiovasc Res 2003, 57:48-54.

(16.) Pfeffer MA, McMurray JJ, Velazquez EJ, et al., Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, Captopril, or Both in Myocardial Infarction Complicated by Heart Failure, Left Ventricular Dysfunction, or Both. N Engl J Med 2003, 349:1893-1906.

(17.) Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013, 128:1810-1852.

(18.) McMurray JJ, Ostergren J, Swedberg K, et al., CHARM Investigators and Committees. Effects of Candesartan in Patients with Chronic Heart Failure and Reduced Left-Ventricular Systolic Function Taking Angiotensin-Converting-Enzyme Inhibitors: The CHARM-Added Trial. Lancet 2003, 362:767-771.

(19.) Ponikowski P, Voors AA, Anker SD, et al., Authors/Task Force Members, Document Reviewers. 2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the Special Contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016, 18:891-975.

(20.) Wan Md Adnan WA, Zaharan NL, Bennett K, Wall CA. Trends in Co-Prescribing of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Ireland. Br J Clin Pharmacol 2011, 71:458-466.

(21.) James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014, 311:507-520.

(22.) Departamento de Salud de Puerto Rico. Plan de Accion de Enfermedades Cronicas para Puerto Rico 2014-2020. San Juan, PR: Division de Prevencion y Control de Enfermedades Cronicas, 2014:1-28.

(23.) American Diabetes Association. Standards of Medical Care in Diabetes--2012. Diabetes Care 2012, 35 Suppl 1:S11-63.

(24.) Executive Summary: Standards of Medical Care in Diabetes--2013. Diabetes Care 2013, 36 Suppl 1:S4-10.

(25.) Chobanian AV, Bakris GL, Black HR, et al., National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 2003, 289:2560-2572.

Denise Figueroa-Rios, PharmD *; Jose J. Hernandez-Munoz, PhD ([dagger]) ([double dagger]); Aileen Garcia-Albarran, PharmD *; Emily A. Garcia-Rodriguez, PharmD *; Glendaliz Mendez-Hernandez, PharmD *; Suzette M. Velez-Rivera, PharmD *

* Department of Pharmacy Practice, School of Pharmacy, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico; ([dagger]) Center for Drug Information and Research, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico; ([double dagger]) Texas A&M University, Irma Lerma Rangel College of Pharmacy, College Station, Texas, United States of America

The author/s has/have no conflict/s of interest to disclose.

Address correspondence to: Denise Figueroa-Rios, PharmD, School of Pharmacy, University of Puerto Rico Medical Science Campus, PO Box 365067, San Juan, PR 00936-5067. Email: denisse.figueroa2@upr.edu
Table 1. Distribution of claims for ACE-Is, ARBs, or antihypertensive
combinations of the 2 (n = 4,042,823).

Therapeutic Class   Frequency   Percent

ACE-I *             2567085     63.50
ARB ([dagger])      951068      23.52
Antihypertensive    524670      12.98
  combinations

* Angiotensin-converting enzyme inhibitor;
([dagger]) Angiotensin II receptor blocker

Table 2. Sociodemographics and primary diagnosis claims distribution
for beneficiaries with at least 1 pharmacy claim for an ACE-I, an
ARB, or a combination product (n = 338,243).

                                     Frequency   Percent
Gender
  Female                             197908      58.51
  Male                               140335      41.49
ASES * region
  East                               55697       16.47
  Metro-North                        49646       14.68
  North                              52216       15.44
  Northeast                          33243       9.83
  San Juan                           20376       6.02
  Southeast                          38292       11.32
  Southwest                          32017       9.47
  Special                            22          0.01
  West                               56734       16.77
Primary diagnosis
  Diabetes                           144619      42.76
  Hypertension                       185570      54.86
  Coronary artery disease            1296        0.38
  Congestive heart failure           6742        1.99
  Chronic kidney disease             16          0.00
Number of claims in the same month
  1                                  302041      89.30
  2                                  34795       10.29
  3                                  1384        0.41
  4                                  23          0.01

* The Puerto Rico Health Services Administration (by its initials in
Spanish)

Table 3. Primary diagnosis and co/prescribing distribution of ACE/I,
ARBs, and/or combination products in a single month for a single
beneficiary (for at least 2 consecutive months) (n = 36,202).

                                         Frequency   Percent
Primary diagnosis
  Diabetes                               16176       44.68
  Hypertension                           18678       51.59
  Coronary artery disease                220         0.61
  Congestive heart failure               1124        3.10
  Chronic kidney disease                 4           0.01
CO-PRESCRIBING
  ACE-I * + ARB ([dagger])               17859       49.33
  ACE-I + COMBO ([dagger]) ([dagger])    7726        21.34
  ARB + COMBO                            5041        13.92
  OTHER COMBINATIONS ([double dagger])   5576        15.40

* Angiotensin-converting enzyme inhibitor; ([dagger]) Angiotensin II
receptor blocker; ([dagger])([dagger]) Combination therapy that
includes an ACE-I or ARB; ([double dagger]) Multiple (>2) drug therapy
combinations.

Table 4. Distribution of beneficiaries who, based on current
guidelines, incorrectly received 2 or more prescriptions for an
ACE-I, ARB, or combination therapy in a single month (for at least 2
consecutive months) (n = 35,078).

                                         Frequency   Percent
Gender
  Female                                 20887       59.54
  Male                                   14191       40.46
ASES * Region
  East                                   5862        16.71
  Metro-North                            5117        14.59
  North                                  5388        15.36
  Northeast                              3641        10.38
  San Juan                               1888        5.38
  Southeast                              3882        11.07
  Southwest                              2929        8.35
  West                                   6371        18.16
Number of claims in the same month
  2                                      33727       96.15
  3                                      1328        3.79
  4                                      23          0.07
CO-PRESCRIBING
  ACE-I ** + ARB ([dagger])              17211       49.06
  ACE-I + COMBO                          7556        21.54
  ARB + COMBO ([dagger]) ([dagger])      4927        14.05
  OTHER COMBINATIONS ([double dagger])   5384        15.35

* The Puerto Rico Health Services Administration (by its initials in
Spanish); ** Angiotensin Converting enzyme inhibitor; ([dagger])
Angiotensin II receptor blocker; ([dagger])([dagger]) Combination
therapy that includes an ACE-I or ARB; ([double dagger]) Multiple
(>2) drug therapy combinations.
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Author:Figueroa-Rios, Denise; Hernandez-Munoz, Jose J.; Garcia-Albarran, Aileen; Garcia-Rodriguez, Emily A.
Publication:Puerto Rico Health Sciences Journal
Date:Jun 1, 2017
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