Latin American Journal of Pharmacy

(formerly Acta Farmacéutica Bonaerense)

Received: February17, 2019
Lat. Am. J. Pharm. 38 (7): 1458-66 (2019) Accepted: May 3, 2019

Prevalence, Predictors and Outcomes of Potential Drug-Drug Interactions

in Patients with Coronary Artery Disease: a Cross Sectional Study
Inamul HAQ1, Mohammad ISMAIL1,*, Fahadullah KHAN1, Qasim KHAN1,2, Zahid ALI1 & Sidra NOOR1

1 Department of Pharmacy, University of Peshawar, Khyber Pakhtunkhwa, Pakistan

2 Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan

SUMMARY. This study aimed to identify the frequency, levels, predictors and clinical consequences of
potential drug-drug interactions (pDDIs) among 400 hospitalized patients with coronary artery disease
(CAD). Micromedex Drug-Reax® was used for identification of pDDIs. Overall-prevalence of pDDIs was
95.5%, while moderate- and major-pDDIs were identified in 91.5% and 90.5% patients, respectively. To-
tal 2757 pDDIs were identified, of which, 49.8% were major-pDDIs and 47.4% were moderate-pDDIs.
Univariate logistic-regression showed significant risk in female for >5 pDDIs (p = 0.013), >3 major-sever-
ity pDDIs (p < 0.001) and increasing hospital-stay (p < 0.001). However, multivariate logistic-regression
showed significant risk of > 5 pDDIs and > 3 major-pDDIs with increasing prescribed medicines (p <
0.001). The most frequent adverse outcomes of pDDIs were chest pain (n = 81), shortness of breath (61),
raised jugular pressure (34), edema (26) and hypotension (24). The study concluded that the prevalence
of pDDIs was considerably high in CAD patients that warrants close monitoring for their prevention and
management.
RESUMEN. El objetivo de este estudio fue identificar la frecuencia, niveles, factores predictivos y las conse-
cuencias clínicas de las posibles interacciones farmacológicas (pDDI) entre 400 pacientes hospitalizados con
enfermedad coronaria (CAD). Se utilizó Micromedex Drug-Reax® para la identificación de pDDI. La prevalen-
cia general de los pDDI fue del 95,5%, mientras que los pDDI moderados y mayores se identificaron en 91,5 y
90,5% de los pacientes, respectivamente. Se identificaron un total de 2757 pDDI, de los cuales, el 49,8% eran
pDDI principales y el 47,4% eran pDDI moderados. La regresión logística univariada mostró un riesgo signifi-
cativo en mujeres para > 5 pDDI (p = 0.013), > 3 pDDI de gravedad mayor (p < 0.001) y aumento de la estancia
hospitalaria (p < 0.001). Sin embargo, la regresión logística multivariable mostró un riesgo significativo de > 5
pDDI y > 3 pDDI principales al aumentar los medicamentos recetados (p < 0,001). Los resultados adversos más
frecuentes de los pDDI fueron dolor en el pecho (n = 81), falta de aliento (61), presión yugular elevada (34),
edema (26) e hipotensión (24). El estudio concluyó que la prevalencia de pDDI era considerablemente alta en
los pacientes con CAD que requieren una estrecha vigilancia para su prevención y manejo.

INTRODUCTION monly prescribed drugs for the management of CAD

Coronary artery disease (CAD) is a major cardio-
vascular illness that arises as a result of lack of oxygen
supply or blood flow to myocardium. In the US,
around 15.5 million people suffer from CAD and one
out of every seven deaths occurs due to CAD 1,2.
Over the past few decades, the prevalence of CAD
has increased from 1.1 to 7.5% and 2.1 to 3.7% in ur-
ban and rural population, respectively 3.
Medication therapy is the most preferred strategy
for managing patients with CAD 4,5. The aim of phar-
macotherapy is to improve quality of life and survival.
Over the past few years, pharmacological therapy of
CAD patients has led to considerable improvement in
CAD associated morbidity and mortality 1,2. Com-
include; antiplatelet drugs, β-blockers, renin-an-
giotensin-aldosterone blockers, calcium-channel
blockers, nitrates, lipid-lowering agents, and α2-ago-
nists 1,4,6-8 . The CAD patients receive lifelong
medicines and often present with old-age and multiple
co-morbidities that increase the probability of
polypharmacy, drug-drug interactions (DDIs) and ad-
verse drug effects 4,5,9-12. DDIs and their associated
adverse effects prolong hospital stay, increase treat-
ment cost and deteriorate quality of life 13.
The incidence of DDIs and its associated ad-
verse effects have a direct relation with increasing
number of prescribed medicines. The incidence of
DDIs ranges from 13% from two drugs to 82% for

KEY WORDS: coronary artery disease, drug safety, pharmacoepidemiology, polypharmacy, potential drug-drug interactions.
* Author to whom correspondence should be addressed. E-mail: ismailrph@uop.edu.pk

ISSN 0326 2383 (printed ed.)

1458 ISSN 2362-3853 (on line ed.)
 Latin American Journal of Pharmacy - 38 (7): 1458-66 (2019)

seven or more drugs 11,13. Whereas, the probability cated, major, moderate and minor) and documenta-
of an interaction is 100% with eight or more drugs tion (excellent, good and fair) levels 20.
10. Hospitalized patients are more prone to DDIs

due to severe medical illness, complex therapeutic Statistical analysis

regimen (polypharmacy) and frequent modification The study variables such as the patients’ gender,
in therapy 14-17. age, hospital stay and number of prescribed medicines
Patients with cardiovascular illness including CAD are presented as frequencies and percentages. Where-
are at higher risk of DDIs and its associated adverse as, median and interquartile range (IQR) are given for
events 13,14, because of lifelong administration of mul- quantitative variables where applicable. The preva-
tiple drugs and the lack of clinical pharmacy services lence and levels of pDDIs are graphically presented.
in majority healthcare settings 4,18,19. Sufficient litera- Logistic regression analysis was applied to estimate
ture is available regarding the issue of DDIs in other the association between various study variables such
cardiovascular illnesses 13,14. However, this issue re- as gender, age, hospital stay and prescribed medicines
mains unaddressed in patients with CAD. Hence, with the presence of > 5 pDDIs (all-types) and > 3
there is a great need for explicit work regarding DDIs major-pDDIs. The odds-ratio (OR) and 95% confi-
and its associated adverse effects in CAD patients dence interval (95% CI) was reported for each vari-
particularly in developing countries in order to pro- able. The SPSS, version-23 was used for the statistical
mote the safe use of drugs by optimizing and moni- analysis and a p-value of 0.05 or less was considered
toring pharmacotherapy for individual patient. statistically significant.
The primary aim of this study was to estimate the
frequency, levels and predictors of pDDIs among RESULTS
hospitalized CAD patients and to develop a list of the Patients characteristics
most frequent pDDIs along with their potential ad- Of the total 400 patients, 55.3% (n = 221) were
verse outcome. Additionally, this study aimed to iden- male and 44.7% (179) were female as shown in Table
tify the possible adverse outcomes of the most fre- 1. Around 33.5% (n = 134) patients were 56-65 years
quent drug interacting pairs. of age, half of the patients (50%, n = 200) were ad-
mitted for ≤ 2 days. While, 28.5% (n = 114) patients
METHODS were prescribed ≤ 7 drugs during their hospital stay.
Study settings and design The median age, hospital stay and number of pre-
A cross-sectional study was conducted in the car- scribed medicines were 60 years (IQR = 51-70), 3
diology wards of two tertiary care teaching hospitals days (2-4) and 10 drugs (7-13), respectively.
of a provincial capital. Characteristics Patients: n (%)
Male 221 (55.3)
Administration and ethical approval Gender
Female 179 (44.7)
A written permission from the administration of
≤ 45 50 (12.5)
each hospital was obtained to access patients’ clinical
46-55 111 (27.8)
profiles. The ethical approval was granted by the In-
56-65 134 (33.5)
stitutional Ethical Committee. Age (Years)
> 65 105 (26.3)
Inclusion and exclusion criteria
Median 60
The clinical profiles of adult (≥ 18 years age) hos-
pitalized patients of either gender, diagnosed with IQR 51.2-69.5
CAD were included in this study. Clinical profiles ≤2 200 (50)
missing the relevant data required for this study were 3-4 108 (27)
excluded. Hospital stay (Days) >4 92 (23)
Median 2.5
Data collection and screening of pDDIs IQR 2-4
Data regarding patient demographic information, ≤7 114 (28.5)
hospital stay, medication therapy, signs, symptoms, 8-10 95 (23.8)
and laboratory/diagnostic findings were collected for Prescribed medications
11-13 95 (23.8)
each patient. The Micromedex Drug-Reax® (Truven > 13 96 (24)
Health Analytics, Greenwood Village, Colorado, Median 10
USA) was used to screen patients’ medication profile IQR 7-13
for pDDIs 20. The Micromedex categorizes the de-
Table 1. General characteristics of study sub-
tected interaction(s) into various severity (contraindi- jects. IQR = Interquartile range.

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HAQ I., ISMAIL M., KHAN F., KHAN Q., ALI Z. & NOOR S.
Frequency of pDDIs
The frequencies of pDDIs are illustrated
in Fig. 1 . Overall, 382 (95.5%) patients were
exposed to at least one pDDI. At least one
moderate- and major-pDDI was identified
in 366 (91.5%) and 362 (90.5%) patients,
respectively, while 9 (2.2%) patients had at
Figure 1. Frequencies of potential drug-drug interactions.
Levels of pDDIs
Overall, 2757 pDDIs were identified in 400
patients. Of which, 1373 (49.8%) and 1306
(47.4%) were of moderate- and major-severity,
respectively. Approximately, 1245 (45.2%)
pDDIs had fair and 1220 (44.3%) pDDIs had
Figure 2. Levels of identified potential drug-drug interactions.
Exposure of pDDIs with respect to patients’
characteristics
Exposure to all-type of pDDIs and major-
severity pDDIs with respect to patients’ charac-
teristics is presented in Table 2 . The prevalence
1460
least one contraindicated-pDDI and 49
(12.2%) patients had at least one minor-pD-
DI. Four or less pDDIs were identified in
151 (37.7%) patients, five to eight pDDIs
were present in 129 (32%) patients and
more than eight pDDIs were present in 120
(30%) patients.
good scientific evidence. Among 2757 pDDIs,
368 distinct interacting pairs were identified. Of
which, 183 (49.7%) and 162 (44%) were of ma-
jor- and moderate-severity, respectively. Where-
as, 202 (55.9%) had fair and 124 (33.7%) had
good scientific evidence, as illustrated in Fig. 2 .
of all-type pDDIs (55.2%) and major-severity
pDDIs (55.8%) were higher in male patients. A
high proportion of patients with all-type pDDIs
and major-severity pDDIs were of 56-65 years
of age (33.5 and 33.7%, respectively), followed
 Latin American Journal of Pharmacy - 38 (7): 1458-66 (2019)

by patients having 46-55 years of age (28.3 and patients prescribed ≤ 7 medicines (27 and
27.6%, respectively). The prevalence of all-type 26.5%, respectively), followed by > 13
pDDIs and major-severity pDDIs was higher in medicines (24.9 and 25.7%, respectively).

Variables All type of pDDIs: n (%) Major-pDDIs: n (%)

Male 211 (55.2) 202 (55.8)
Gender
Female 171 (44.8) 160 (44.2)
≤ 45 48 (12.6) 46 (12.7)
46-55 108 (28.3) 100 (27.6)
Age (years)
56-65 128 (33.5) 122 (33.7)
> 65 98 (25.7) 94 (26)
≤2 188 (49.2) 178 (49.2)
Hospital stay
3-4 105 (27.5) 99 (27.3)
(days)
>4 89 (23.3) 85 (23.5)
≤7 103 (27) 96 (26.5)
Prescribed 8-10 90 (23.6) 86 (23.8)
medicines 11-13 94 (24.6) 87 (24)
> 13 95 (24.9) 93 (25.7)
Table 2. Exposure to potential drug-drug interactions stratified according to patients’ characteristics. pDDIs = potential
drug-drug interactions.

Predictor of pDDIs nearly twice in females patients than males. The

Univariate logistic regression analysis estimat-
ed a significant association between > 5 pDDIs
and > 3 major-severity pDDIs with gender, hos-
pital stay and prescribed medicines as presented
in Table 3 . The risk of > 5 pDDIs (p = 0.013)
and > 3 major-severity pDDIs (p < 0.001) were
risk of > 5 pDDIs and > 3 major-severity
pDDIs increased significantly with increasing
hospital stay (p < 0.001). Likewise, a significant
increase in the risk of > 5 pDDIs and > 3 major-
severity pDDIs was observed with increasing
number of prescribed medicines (p < 0.001).

> 5 pDDIs > 3 Major-pDDIs

Variables
OR 95% CI P OR 95% CI P
Male Reference Reference
Gender
Female 1.7 1.1-2.5 0.013 2 1.3-3 0.001
≤ 45 Reference Reference
Age 46-55 1.1 0.6-2.1 0.791 1 0.5-1.9 0.897
(Years) 56-65 1.1 0.6-2.2 0.718 1.1 0.6-2.2 0.777
> 65 1 0.5-2 0.956 1 0.5-2 0.991
≤2 Reference Reference
Hospital stay
3-4 2.5 1.6-4.1 < 0.001 2.5 1.5-4.1 < 0.001
(Days)
>4 3.7 2.2-6.2 < 0.001 4 2.4-6.7 < 0.001
≤7 Reference Reference
Prescribed 8-10 8.2 3.8-17.7 < 0.001 11.8 3.4-40.8 < 0.001
medicines 11-13 29.1 13.2-64.4 < 0.001 46.7 13.8-157.5 < 0.001
>13 80.4 32.6-198.3 < 0.001 132.1 38.1-458.8 < 0.001
Table 3. Univariate logistic regression analysis based on exposure to > 5 pDDIs and > 3 Major-pDDIs. pDDIs = potential
drug-drug interactions; OR = odds ratio; CI = confidence interval.

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HAQ I., ISMAIL M., KHAN F., KHAN Q., ALI Z. & NOOR S.

Following multivariate logistic regression anal- number of prescribed medicines (p < 0.001) as
ysis, the risk of > 5 pDDIs and > 3 major-severity shown in Table 4. In contrast, no significant asso-
pDDIs increased significantly with increasing ciation was estimated for gender and hospital stay.

> 5 pDDIs > 3 Major-pDDIs

Variables
OR 95% CI P OR 95% CI P
Male Reference Reference
Gender
Female 1.2 0.7-2 0.441 1.6 1-2.7 0.071
≤2 Reference Reference
Hospital stay
3-4 0.9 0.5-1.6 0.596 0.9 0.5-1.6 0.671
(days)
>4 0.6 0.3-1.3 0.216 0.8 0.4-1.5 0.44
≤7 Reference Reference
Prescribed 8-10 8.9 4.1-19.4 < 0.001 12.3 3.5-43.1 < 0.001
medicines 11-13 31.9 13.9-73.3 < 0.001 48.4 14-167.1 < 0.001
>13 103.2 37-288 < 0.001 149.3 39.6-563.2 < 0.001
Table 4. Multivariate logistic regression analysis based on exposure to > 5 pDDIs and > 3 Major-pDDIs.
pDDIs = potential drug-drug interactions; OR = odds ratio; CI = confidence interval.

Widespread interacting drug combinations of bleeding, reduced therapeutic effectiveness,

The most frequent drugs involved in pDDIs
were aspirin, clopidogrel, nitroglycerin, biso-
prolol, furosemide and ramipril as shown in
Table 5 . The potential adverse outcomes of the
most frequent interactions were increased risk
increased blood pressure, hyperkalemia, ECG
changes, nephrotoxicity, digoxin toxicity, hypo-
glycemia, electrolyte disturbances, increased
risk of myopathy or rhabdomyolysis, and in-
creased blood pressure.

DDIs Pair Frequency* Severity Evidence Description

Aspirin-Clopidogrel 250 Major Fair Increased risk of bleeding

Aspirin-Nitroglycerin 223 Moderate Good Increase in Nitroglycerin concentrations

and additive platelet function depression
Aspirin-Bisoprolol 148 Moderate Good Increased blood pressure.

Aspirin-Furosemide 146 Major Good Reduced diuretic effectiveness and

possible nephrotoxicity
Aspirin-Ramipril 126 Moderate Fair Decreased Ramipril effectiveness
Clopidogrel-Enoxaparin 120 Major Fair Increased risk of bleeding
Furosemide-Ramipril 92 Moderate Good Postural hypotension (first dose)

Aspirin-Spironolactone 90 Major Good Reduced diuretic effectiveness, hyperkalemia,

or possible nephrotoxicity
Decreased formation of Clopidogrel active
Atorvastatin-Clopidogrel 88 Moderate Excellent metabolite resulting in high on-treatment platelet
reactivity
Ramipril-Spironolactone 67 Major Good Hyperkalemia

Digoxin-Furosemide 50 Moderate Fair Increased risk of digoxin toxicity

(nausea, vomiting, cardiac arrhythmias)
Aspirin-Insulin 48 Moderate Fair Increased risk of hypoglycemia
Digoxin-Spironolactone 42 Major Good Increased digoxin exposure

Clopidogrel-Omeprazole 40 Major Excellent Reduction in clinical efficacy of Clopidogrel

and increased risk for thrombosis

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 Latin American Journal of Pharmacy - 38 (7): 1458-66 (2019)

Aspirin-Digoxin 36 Major Fair Increased serum concentration of digoxin;

prolonged half-life of digoxin

Clopidogrel-Esomeprazole 36 Major Excellent Reduced plasma concentrations of

Clopidogrel active metabolite
Albuterol-Furosemide 34 Moderate Fair ECG changes or hypokalemia
Aspirin-Carvedilol 34 Moderate Good Increased blood pressure.
Aspirin-Calcium 30 Moderate Fair Decreased salicylate effectiveness
Aspirin-Streptokinase 30 Moderate Excellent Increased risk of hemorrhagic complications
Enoxaparin-Streptokinase 28 Major Fair Increased risk of bleeding
Insulin-Ramipril 26 Moderate Fair Increased risk of hypoglycemia

Bisoprolol-Insulin 22 Moderate Good Hypoglycemia or hyperglycemia;

Decreased symptoms of hypoglycemia
Multivitamin-Rosuvastatin 19 Major Good Increased risk of myopathy or rhabdomyolysis
Aspirin-Glimepiride 17 Major Fair Increased risk of hypoglycemia
Aspirin-Metoprolol 17 Moderate Good Increased blood pressure.
Cyanocobalamin-Omeprazole 16 Minor Good Decreased cyanocobalamin absorption

Digoxin-Omeprazole 15 Moderate Good Increased risk of digoxin toxicity

(nausea, vomiting, arrhythmias)
Domperidone-Moxifloxacin 15 Major Fair Increased risk of QT interval prolongation

Bisoprolol-Glimepiride 15 Moderate Good Hypoglycemia or hyperglycemia;

decreased symptoms of hypoglycemia
Table 5. Most frequently identified interactions, their levels and potential adverse outcomes. ECG = electrocardiogram.
* Frequencies represent the number of patients presented with respective drug interacting pair out of the total 400 hospital-
ized CAD patients.

Clinical relevance signs/symptoms and abnormal laboratory find-

The adverse clinical findings associated with
ten most frequent drug interacting pairs and
their monitoring/management strategies 20-22 are
presented in Table 6 . Considerable number of
patients taking aspirin plus clopidogrel or as-
pirin plus nitroglycerin were presented with
ings for bleeding. Elevated blood pressure was
observed in patients taking aspirin plus bisopro-
lol or aspirin plus ramipril. Signs/symptoms and
abnormal laboratory findings for nephrotoxicity
were observed in patients taking aspirin plus
furosemide combination.

Laboratory
Interactions Signs and
S.No Investigations Monitoring, Management guidelines 20-22
(n) symptoms (n) (n)

Raised JVP (10) Hemoglobin: Low (08), Nor- Patients should be monitored for signs and
Anemia (08) mal (07) symptoms of bleeding and close assessment
Aspirin + Orthopnea (08) Platelets Count: Low (05), of blood counts. Caution is advised while
1 Clopidogrel Melena (03) Normal (05) using this combination, owing its increased
(250) Bleeding per rectum (02) INR: High (07) risk of thrombotic events, therefore copre-
Hemoptysis (01) PT: High (07) scription may be considered carefully.
APTT: High (03)

Hemoglobin: Low (07), Nor-

Hypotension (14) mal (03) The combination may benefit the patients
Aspirin + Vomiting (10) Platelets: Low (03), Normal with acute myocardial infarction (AMI).
2 Nitroglycerin Headache (07) (03) Nevertheless, monitoring for an exaggerat-
(223) Dizziness (03) BUN: Normal (03), High (10) ed response to nitroglycerin (headache, syn-
Vertigo (01) Serum Creatinine: Normal cope) and platelet function is advised.
(04), High (09)

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HAQ I., ISMAIL M., KHAN F., KHAN Q., ALI Z. & NOOR S.

Chest Pain (14) BUN: Normal (04), High (06)

SOB (12) Serum Creatinine: Normal Monitoring of blood pressure is advised. In
Aspirin + Increased blood pressure (04), High (06) heart failure, the beta blockers are consid-
3 Bisoprolol (04) INR: High (02) ered to be narrow therapeutic index. Con-
(148) Headache (04) PT: High (02) comitant use of NSAIDs should generally
Raised JVP (03) APTT: High (01) be avoided in patients with heart failure.
Edema (03)

SOB (25) BUN: Normal (03), High (13)

Aspirin + Chest Pain (13) Serum Creatinine: Normal Patients should be monitored for signs of
4 Furosemide Raised JVP (10) (04), High (12) worsening renal function, diuretic efficacy,
(146) Edema (07) Serum Sodium: High (02) appropriate effects on blood pressure and
Increased blood pressure Serum Potassium: High (05) high dose aspirin should be avoided.
(06)

Aspirin may result in reduced ramipril effec-

Chest Pain (15) BUN: Normal (03), High (08) tiveness. Patient’s blood pressure and hemo-
Aspirin + SOB (14) Serum Creatinine: Normal dynamic parameters should be monitored.
5 Ramipril Raised JVP (06) (04), High (07) Consider the following option in case of any
(126) Edema (04) Serum Sodium: High (04) adverse effect; (a) aspirin dosage less than
Dizziness (02) Serum Potassium: High (02) 100 mg per day (b) an alternative non-as-
Irritability (02) pirin antiplatelet agent (c) replacing ACE in-
hibitors with angiotensin receptor blockers.

Chest Pain (15) Hemoglobin: Low (03), Nor- Prompt evaluation for signs or symptoms
Clopidogrel + Nausea
Anemia
& Vomiting (10)
(08) mal (03) of bleeding is advised.
6 Enoxaparin Edema (04) INR: High (03) Additionally, if possible discontinue the an-
(120) Melena (01) PT: High (03) tiplatelet agent prior to initiating a low
Bleeding per rectum (01) APTT: High (01) molecular weight heparins (LMWHs).

The patients with sodium depletion and hy-

povolemia are at high risk. Closely monitor
Hypotension (10) blood pressure of the patients for a severe
Orthopnea (04) BUN: Normal (01), High (08) hypotensive response for four hours after
7 Furosemide + Edema (04) Serum Creatinine: Normal the initial dose. Temporarily discontinue
Ramipril (92) Dizziness (02)
Nausea (01)
(02), High (08)
Serum Sodium: Low (03),
furosemide and/or the patient should be
started at very low dose angiotensin con-
Vomiting (06) Normal (03) verting enzyme (ACE) inhibitors, particu-
Cough (09) larly in evening; monitor for hypotension,
fluid status, and body weight regularly for
up to two weeks after dose adjustments.

Platelets Count: Low (02), Patients should be monitored for signs of

Cough (16) Normal (01) worsening renal function, diuretic efficacy
Aspirin + Orthopnea (08) BUN: Normal (01), High (06) and blood pressure in patients chronically
8 Spironolactone Edema (04) Serum Potassium: Normal receiving spironolactone and salicylates.
(90) Chest Pain (09) (03), High (03) The effects of interaction can be reversed
Raised JVP (08) Serum Creatinine: Normal by increasing the spironolactone dose.
(03), High (05)

Platelets Count: Low (04), The effects of interaction between these

Atorvastatin + Chest Pain (08) Normal (04) agents appears to be dose related. Caution
9 Clopidogrel SOB (05) BUN: Normal (03), High (06) should be exercised while giving higher
(88) Cough (04) Serum Creatinine: Normal doses of clopidogrel as 300mg and atorvas-
Headache (04) (03), High (06) tatin as 80mg in coprescription.
Serum Potassium: High (02)

Patients should be monitored for persistent

Chest Pain (07) elevations of serum potassium, especially in
Ramipril + Increased blood pres sure BUN: Normal (01), High (03) patients with renal dysfunction or diabetes
10 Spironolactone (04) Serum Potassium: High (02) and the elderly; which can lead to severe ar-
(67) Cough (06) Serum Creatinine: High (03) rhythmias and death. In patients receiving
co-prescription (ramipril & spironolactone);
Hyperkalemia (03) spironolactone may be used 25 mg daily or
on alternate day.

Table 6. Top ten interactions, their clinical relevance and monitoring/management guidelines. JVP = jugular venous pres-
sure, SOB = shortness of breath, BUN = blood urea nitrogen, INR = international normalized ratio, PT = prothrombin
time, APTT = activated partial thromboplastin time, LMWHs = low molecular weight heparins.

1464

DISCUSSION
Overall higher prevalence of pDDIs (95.5%)
has been identified in the present study as com-
pared with studies for other cardiovascular dis-
ease such as heart failure (88%) 14 , and in gener-
al cardiology ward (77.5%) 23 . These differences
may be attributed to variable study design, na-
ture of study subjects, drug prescribing patterns
and drug interaction tools. Moreover, the preva-
lence of pDDIs in the present study is higher in
comparison to studies conducted for other med-
ical illnesses and hospital wards 17-19,24-27 , mainly
because of higher propensity for interactions as-
sociated with cardiovascular drugs 10-12 .
Unlike the developed world, drug related
problems including DDIs and its associated ad-
verse outcome remains a major health care con-
cern because of unavailability of clinical phar-
macy services and DDIs screening programs in
majority of hospital 19 . Moreover, irrational use
of medicines, poor access to health care facili-
ties and overburdened health care professionals
are the predominant factors for drug related
problems 18,19 .
The findings of this study require thoughtful
consideration regarding pDDIs particularly in
hospitalized patients with CAD. Screening of
patients’ medication profile using computerized
based screening tools 11,15 , clinical pharmacist
participation in patients evaluation of pDDIs
11,28,29 , vigilant monitoring of pDDIs related ad-
verse outcomes 30 , continuous medical education
regarding pDDIs to health care professionals
10,11 and establishment of hospital based drug in-
formation center are some of the strategies to
promote the judicious use of multiple drugs and
prevent drug related adverse outcomes 10 .
Severity of pDDIs is an important factor for
assessing and managing their associated adverse
outcome. In the present study, majority of the
pDDIs were of moderate- and major-severity,
which are consistent with the findings of other
studies among patients with cardiovascular ill-
nesses including heart failure 13,14,23 . Moreover,
similar results have also been reported for pa-
tients admitted in other wards 18,19,27 . It is im-
portant for healthcare professionals to identify
pDDIs, particularly those having moderate- and
major-severity levels in order to prevent and
manage their associated adverse outcome.
The use of multiple medicines is inevitable
in CAD patients, mainly because of old age and
the presence of co-morbidities that significant-
ly increase the risk of pDDIs and its associated
Latin American Journal of Pharmacy - 38 (7): 1458-66 (2019)
adverse effects among these patients 17,24,25 . We
found a significant association of all-type of
pDDIs and major-pDDIs with increasing num-
ber of drugs, which are consistent with findings
of other studies 18,19,27,31 . Therefore, such pa-
tients must be screened for pDDIs, preferably
through a computer based DDIs screening
tool. Such screening is crucial before prescrib-
ing and administering drugs in order to identify
problems in advance to prevent and manage
them accordingly.
List of most frequent pDDIs and their po-
tential adverse effects will guide the overbur-
dened healthcare professionals in selecting safer
therapies and screening of pDDIs 9 . Moreover,
such information will enable healthcare profes-
sionals to develop strategies for the identifica-
tion, prevention and management of pDDIs and
their associated adverse effects.
The potential limitations of this study in-
clude the cross-sectional nature of the study
without a follow-up, which limited an in-depth
insight into associated clinical outcomes and ad-
verse effects of pDDIs. Furthermore, a number
of DDI screening tools are available but we
used a single DDI screening tool, the Mi-
cromedex Drug-Reax®. Multicenter studies with
proper follow-up are recommended to further
highlight the importance of DDI screening in
hospitalized patients with CAD.
CONCLUSION
The prevalence of pDDIs was considerably
high in CAD patients. Majority of interactions
were of moderate- and major-severity. Patients
with extended hospital stay and increased num-
ber of prescribed medicines were at higher risk
of pDDIs. Strict patient monitoring is necessary
in hospitalized CAD patients in order to prevent
and manage negative clinical outcomes associat-
ed with these interactions. The list of most fre-
quent pDDIs and clinical relevance will aid in
targeted screening, prevention and management
of pDDIs and their associated adverse effects.
Acknowledgement
The authors would like to thank the administration,
consultants and all other staff of the hospitals for
their cooperation in this study.
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