Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Thiruvalla, Kerala
On Sep 2018

Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."

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Chairman, Research Group, Charutar Arogya Mandal, Karamsad
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Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018

Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."

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Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
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Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
On Sep 2018

Dr. Arunava Biswas

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Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."

Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
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Calcutta National Medical College & Hospital , Kolkata

Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
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Muzaffarnagar Medical College,
On Aug 2018

Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".

Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
On Aug 2018

Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".

Dr. Mamta Gupta
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018

Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.

Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."

Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."

Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : OC22 - OC25 Full Version

Effectiveness and Safety of Fixed-dose Combination of Perindopril/Amlodipine/Indapamide, and Telmisartan/Amlodipine/Chlorthalidone in Grade 2 Hypertensive Patients at High Cardiovascular Risk: A Real-world Observational Study

Published: January 1, 2023 | DOI:
Shambo Samrat Samajdar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Shashank Joshi

1. Clinical Pharmacologist, Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India. 2. Assistant Professor, Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India. 3. Dean and Professor, Department of Pharmacology, Netaji Subhash Medical College and Hospital, Patna, Bihar, India. 4. Professor, Department of Medicine, R G Kar Medical College and Hospital, Kolkata, West Bengal, India. 5. Senior Consultant Endocrinologist, Department of Endocrinology, Joshi Clinic, Mumbai, Maharashtra, India.

Correspondence Address :
Dr. Shambo Samrat Samajdar,
Consultant at Diabetes & Allergy-Asthma Therapeutics Specialty Clinic;
Department of Clinical and Experimental Pharmacology, School of Tropical
Medicine, Kolkata, West bengal, India.


Introduction: Fixed-dose combination containing triple antihypertensive agents (Angiotensin-Converting Enzyme Inhibitor (ACE-I)/Angiotensin Receptor Blocker (ARB), diuretic and Calcium Channel Blocker (CCB)) is recommended to achieve target Blood-Pressure (BP). However, none of the study has compared ACE-I based and ARB-based triple fixed dose combinations.

Aim: To evaluate the effectiveness and safety of fixed-dose combination of Perindopril (Per)/Amlodipine (Aml)/Indapamide (Ind) and Telmisartan (Tel)/Aml/Chlorthalidone (Chl) in grade-2 hypertensive patients at high Cardiovascular (CV) risk.

Materials and Methods: This retrospective, observational, single-centre study enrolled treatment-naïve grade-2 hypertensive patients who were at high CV risk and were treated with ACE-I based (Per/Aml/Ind; Per/Aml/Ind group) or ARB-based (Tel/Aml/Chl; Tel/Aml/Chl group) triple fixed-dose combination for atleast one-month at the study centre. Office Blood Pressure (BP) at one-month follow-up was used as a parameter to measure treatment effectiveness. Safety was assessed based on the occurrence of Adverse Events (AEs).

Results: A total of 69 patients (n=32 in Per/Aml/Ind group and n=37 in Tel/Aml/Chl group) were included. Office Systolic BP (SBP)/Diastolic BP (DBP) were 181.44±8.52/95.19±7.25 mmHg and 183.32±6.65/94.81±7.14 mmHg in patients belonging to Per/Aml/Ind and Tel/Aml/Chl groups, respectively. There was a significant reduction in office SBP/DBP at one-month follow-up (Per/Aml/Ind: 129.31±6.44/75.06±4.85 mmHg and Tel/Aml/Chl: 129.10±5.90/75.00±4.82 mmHg; p-value=0.0001). Between-group comparisons did not showed any significant difference in terms of reducing office BP. Both groups exhibited identical safety profile.

Conclusion: The study demonstrated comparable treatment effectiveness and safety profile with triple fixed dose combinations containing Per/Aml/Ind and Tel/Aml/Chl in a real-world setting.


Angiotensin-converting enzyme inhibitor, Angiotensin receptor blocker, Calcium channel blocker, Diuretic, Hypertension, Triple fixed-dose combination

Hypertension is a major health burden worldwide with an estimated global prevalence of 1.5 billion by 2025 (1). Among all CV risk factor, it is identified as the leading cause of mortality worldwide (2). However, randomised controlled trials confirmed that effective BP lowering is associated with improved outcomes in terms of reduction of coronary heart disease, stroke, heart failure, CV death and all-cause death (3),(4),(5). Hence, optimum BP control is of paramount importance. Several factors contribute to the development of hypertension, including increased circulating volume, sympathetic hyperactivity, increased total peripheral vascular resistance, and abnormal over-activity of the Renin Angiotensin Aldosterone System (RAAS) (6). Hence, to control BP effectively, the concomitant administration of two or more antihypertensive medications from different pharmacological classes that target multiple pathways is necessary (7),(8). Notably, upto 60% patients fail to achieve target BP control with dual antihypertensive agents (9). In this scenario, initiating hypertension treatment with triple fixed-dose combination seems a promising approach. Apart from proven safety and efficacy, fixed-dose combination therapy improves treatment adherence due to regimen simplification and thereby reduce patient, physician and healthcare system barriers related to multiple visits and prolonged titration schedules. Cost-effectiveness is another advantage of the fixed-dose combination therapy.

The ideal candidates for triple fixed dose combination include a RAAS inhibitor (ACE-I or ARB), a CCB and a diuretic. Among CCB, amlodipine is identified as the most-effective antihypertensive, either alone or in combination with other drug class (10). While selecting diuretics, thiazide like diuretics (chlorthalidone and indapamide) is preferred over thiazide diuretics due to longer plasma half-life, neutral effect on metabolism and efficacy in preventing CV events (11). However, the selection between ACE-I and ARB is challenging. From pathophysiological effects perspective, ACE-I seems superior as compared to ARB (10). However, clinical studies reported controversial findings. Besides, as compared to ACE-I, ARBs have lower drug-related AEs leading to reduced rates of treatment discontinuation (10). The safety and efficacy of the ACE-based and ARB-based triple fixed dose combinations in reducing BP has been well-established. Till date, no head-to-head study compares ARB-based and ACE-I-based triple fixed dose combinations. Hence, this study was designed to bridge this gap and report results using Per/Aml/Ind (an ACE-based triple fixed-dose combination) and Tel/Aml/Chl (an ARB-based triple fixed-dose combination) in grade-2 hypertensive patients who were at high CV risk in routine clinical settings.

Material and Methods

A retrospective, observational, single-centre study was conducted at the Diabetes and Allergy-Asthma Therapeutics Specialty Clinic, Kolkata, West Bengal India, from November 2020 to February 2021.The data analysis was carried out after 15 days of study period.

The study was approved by the Institutional Ethics Committee (IEC) (Human Research Ethics committee, Allergy and Asthma Research Centre, Kolkata; approval number: HREC-AARC/15) and was conducted in accordance with the regulatory requirements and Good Clinical Practice guidelines. The waiver for informed consent from the study participants was received from IEC.

Inclusion criteria: Patients on treatment-naïve and newly diagnosed grade-2 hypertensive patients with age ≥18 years who were at high CV risk, if they were prescribed single pill of fixed-dose triple combination of Per/Aml/Ind or Tel/Aml/Chl for atleast one month at the study centre. Treatment naïve newly diagnosed hypertensive patients with BP >160 mmHg or and >100 mmHg along, with any one risk factors like age (>65 years), sex (male>female), heart rate (>80 beats/min), obesity, diabetes, high Low Density Lipoprotein-Cholesterol (LDL-C)/triglyceride, family history of Cardiovascular Disease (CVD), family history of hypertension, early-onset menopause, smoking habits, psychosocial or socio-economic factors, having completed one month therapy in a therapeutics clinic.

Exclusion criteria: Patients whose one-month follow-up data was incomplete, were excluded from the study.

Data was recorded by the treating physician. Grade-2 hypertension was defined as SBP ≥160 mmHg and DBP ≥100 mmHg. The CV risk was calculated according to practice guideline of hypertension guidelines or the management of hypertension developed by International Society of Hypertension (ISH) (12).

Methodology: The patients were identified through online database of outpatients. The records were divided into two groups. The patients receiving a triple fixed-dose combinations of Per/Aml/Ind (5/1.25/5 mg or 5/1.25/10 mg or 10/2.5/5 mg or 10/2.5/10 mg) constituted the Per/Aml/Ind group, whereas patients receiving Tel/Aml/Chl (40/5/12.5 mg) constituted the Tel/Aml/Chl-group.

Patient medical records were examined retrospectively to collect all relevant data including demographics, CV risk factors, office SBP/DBP, and laboratory measurements at baseline and at one month. Information related to AEs was collected through verbal communication with the treating physician, patient and his/her caretaker. Data were collected using predefined case report form by a study coordinator.

Statistical Anlaysis

Categorical variables were presented as frequencies and percentages, and continuous variables were presented using mean ±standard deviation. Comparison was performed using paired t-test (within group), unpaired t-test (between two groups) or Chi-square test depending upon the types of variables. A p-value <0.05 was considered statistically significant. Statistical analysis was performed by using Statistical Analysis System (SAS).


From the database, data of 69 patients were included in this study. Of 69, 32 patients were in the Per/Aml/Ind group, and 37 patients in Tel/Aml/Chl group. The mean age of patients in Per/Aml/Ind and Tel/Aml/Chl groups was 57.06±7.51 years and 57.08±6.98 years, respectively. There was a statistically insignificant difference with respect to co-morbidities between both groups (Table/Fig 1).

For Per/Aml/Ind group, the mean office SBP decreased significantly from baseline to one-month follow-up (181.44±8.52 mmHg vs. 129.31±6.44 mmHg; p-value=0.0001). Similarly, mean DBP in this group decreased significantly from 95.19±7.25 mmHg at baseline to 75.06±4.85 at one-month follow-up. On the other hand, for the Tel/Aml/Chl group, mean office SBP reached 129.10±5.90 mmHg at one month follow up from 183.32±6.65 mmHg at baseline , with a significant change at p-value=0.0001). Similarly, mean DBP for this group significantly reduced from 94.81±7.14 mmHg at baseline to 75.00±4.82 mmHg at one month follow-up (p-value=0.0001) (Table/Fig 2).

(Table/Fig 3) shows changes in biochemical/laboratory parameters at one-month follow-up from baseline. Mean change in creatinine levels was slightly higher in Tel/Aml/Chl group as compared to Per/Aml/Ind group, with statistically significant change observed for Tel/Aml/Chl group at p-value=0.0056. At one-month follow-up, there was a significant reduction (p-value=0.0030) in sodium level from 139.97±2.09 mEq/L at baseline to 138.81±1.87 mEq/L at one-month follow-up in Per/Aml/Ind group. Similarly, there was a significant (p-value=0.0009) reduction in sodium level from 140.05±2.22 mEq/L at baseline to 136.43±5.86 mEq/L in Tel/Aml/Chl group. Patients in the Tel/Aml/Chl group were likely to experience significant reduction in sodium level (p-value=0.0009). There was no significant change in potassium level in either group at one-month follow-up.

At one-month follow-up, there was no incidence of serious AE. In the Per/Aml/Ind group, reported AEs were occurrence of cough (n=2), dyselectrolyemia (n=1) and pedal oedema (n=2). No patient in Tel/Aml/Chl group experienced any incidence of cough. However, dyselectrolyemia and pedal oedema were noted in 7 and 2 patients in Tel/Aml/Chl group, respectively (Table/Fig 4).


Hypertension is a pressing global health issue. It is associated with increase in peripheral vascular resistance that, in turn, can lead to CV morbidities and mortality, if not identified early and treated properly. Triple fixed-dose combination of an ACE-I/ARB, diuretic and a CCB is recommended to treat uncontrolled hypertension by several guidelines [12-14]. Theoretically, these combinations possess several advantages: 1) combining RAAS inhibitor with diuretics produces additive effects on BP reduction; 2) improved tolerability profile of antihypertensive therapy i.e., RAAS inhibitor counteracts diuretic-induced adverse impacts on electrolytes, uric acid and glucose metabolism as well as CCB-induced peripheral oedema; 3) RAAS activation through combination of CCB and diuretics can be mitigated by adding RAAS-inhibitors (15). Thus, combining these agents may prove beneficial to achieve target BP.

The selection between ACE-I and ARB seems a hard target to deal with. While ARBs have a more favourable tolerability profile, with lower rates of cough or angiooedema, clinical benefits are found higher with ACE-I than with ARB (16). A meta-analysis assessing clinical benefits of ACE-I and ARB in 158,998 hypertensive patients from 20 contemporary hypertension trials demonstrated that the use of ACE-I was associated with reduction of all-cause mortality and CV mortality (17). A meta-analysis involving diabetic patients found that ACE-I, but not ARB, reduced all-cause mortality, CV mortality, and major adverse CV events (18). In contrast, the results of ONTARGET, the largest randomised controlled trial, reported equal efficacy of ACE-I (ramipril) and ARB (Tel) at reducing CV events and mortality in patients with CVD or high-risk diabetes (19). An increasing number of evidence did not find any difference in efficacy between ARB and ACE-I at BP reduction, heart failure symptoms improvement and stroke reduction (20). Intraclass variability in pharmacodynamic and pharmacokinetic properties in ARB class may also contribute to the inconsistency in therapeutic effects as well as clinical outcomes beyond BP control (20). All the aforementioned findings/evidence was based on the trials involving each agent (ACE-I/ARB) alone. None of the study compared ACE-based and ARB-based triple fixed dose combination. Present study was designed to compare effectiveness and safety of ACE-based triple fixed dose combination and ARB-based triple fixed dose combination.

Results of the present study confirmed effectiveness and safety of both triple fixed-dose combinations containing Per/Aml/Ind and Tel/Aml/Chl from the outpatient database of treatment-naïve grade-2 hypertensive patients who were at high CV risk. Both, ACE-I based and ARB based single pill fixed-dose combinations, were effective in reducing office BP without any clinically significant interference in biochemical parameters at one-month follow-up. At one-month follow-up, the reduction in SBP and DBP in patients treated with ACE-based triple fixed dose combination was found to be 52.13 mmHg and 20.13 mmHg, respectively. For patients receiving ARB-based triple fixed dose combination, the reduction in SBP and DBP was 54.24 mmHg and 19.81 mmHg, respectively. Present study found non significant difference in reduction in SBP and DBP between two fixed dose combinations that could be attributed by small sample size. There were no incidences of serious AEs.

The reductions in BP observed in the present study were consistent with other studies (21),(22),(23),(24),(25),(26),(27),(28). The Per/Aml/Ind is the most extensively evaluated triple fixed dose combination. Randomised double-blind, controlled trials demonstrated significant BP reduction with triple fixed dose combination containing Per/Aml/Ind as compared to dual antihypertensive therapy in different subgroup of hypertensive patients (29),(30). The‘Perindopril-Amlodipine plus Indapamide Combination for Controlled Hypertension—Non Intervention Trial’ (PAINT) study which included 6088 patients with uncontrolled hypertension demonstrated significant BP reduction (SBP/DBP: 26.7±13.3/12.9±9.4 mmHg; p=0.001) with Per/Aml/Ind at 4-month follow-up (27). The findings of‘ Perindopril-Indapamide plus Amlodipine in High Risk Hypertensive Patients’ (PIANIST) study extended safety and effectiveness of this single-pill triple fixed-dose combination in hypertensive patients (N=4731) who were at high or very high CV risk (28). The SBP/DBP reduction was found to be 28.3±13.5/13.8±9.4 (p=0.0001) after 4-month therapy with Per/Aml/Ind. Thacker H et al., demonstrated BP reduction of 28.5/13.8 mmHg in patients with uncontrolled hypertension in Indian scenario (31).

Other real-world studies also demonstrated BP-lowering effectiveness and safety of Per/Aml/Indin a large pool of hypertensive patients (26),(27),(28),(29),(30),(31),(32). Similarly, efficacy and safety of ARB-based study have been confirmed in several studies. Randomised controlled trial evaluating effectiveness of ARB-based triple therapy with Aml, Valsartan (Val) and hydrochlorthiazide (HCTZ) (10/320/25 mg) in patients with BP ≥145/100 mmHg showed significant reductions in SBP/DBP of 39.7/24.7 mmHg at 8 week follow-up (22). A randomised controlled trial, ‘Triple Therapy with Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide in Hypertensive Patients Study’ (TRINITY), showed reduction of 37.1/21.8 mm Hg in SBP/DBP with the ARB-based triple therapy at 12-week follow-up (24). Triple antihypertensive therapy containing Aml/Tel/HCTZ (5/40/12.5 mg) found efficacious in reducing BP in patients with moderate to severe hypertension (23). The effectiveness of ARB-based triple therapy at reducing BP has been confirmed in real world setting also (21),(25),(26),(27),(28). Of note, while the effectiveness of the ARB-based triple therapy is awaited, ACE-based triple therapy shows substantial reduction in CV risk using Per/Aml/Ind (33). The trials and real-world studies demonstrate similar tolerability profiles with ACE-based and ARB-based triple fixed dose combinations (15).


The study possesses inherent limitations of an observational study and small-sized treatment groups were another major limitation. Though the effectiveness of antihypertensive medications can be assessed accurately through ambulatory BP monitoring, which could not be performed in this study. Furthermore, the impact of lifestyle changes or adherence to antihypertensive medications was not assessed. Despite these limitations, the results of the study provide an evidence of safety and effectiveness of single-pill fixed-dose triple combinations of antihypertensive medications in routine clinical practice.


Results derived from the data for the present study provides strong evidence for safety and effectiveness of fixed-dose triple combinations containing Per/Aml/Ind and Tel/Aml/Chl in treatment-naïve hypertensive patients in a real-world scenario. The combinations were well tolerated and no incidences of serious AEs were reported. However, a large-scale study may be needed to reiterate long-term safety and clinical outcomes of these triple fixed dose combinations.


The authors would like to acknowledge Dr. Leena Patel and Arohi Sarang from CBCC Global Research for their writing and editorial support in the development of this manuscript.


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DOI and Others

DOI: 10.7860/JCDR/2023/58211.17345

Date of Submission: Jun 16, 2022
Date of Peer Review: Jul 21, 2022
Date of Acceptance: Oct 26, 2022
Date of Publishing: Jan 01, 2023

• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA

• Plagiarism X-checker: Jun 20, 2022
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