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Insights from Clinical Practice Insights from Clinical Practice

Insights from Clinical Practice

References The Indian ‘Polycap’ Study (TIPS)12 1. Prabhakaran D, Jeemon P, et al. Cardiovascular Diseases in India: Current Epidemiology and Future 1) Significantly higher reduction in systolic and diastolic BP with ‘Polycap’ Directions. Circulation. 2016 Apr 19;133(16):1605-20. ISSUE 1 as compared to groups not receiving BP lowering drugs and those with 2. Lafeber M, Spiering W, et al. Multifactorial Prevention of Cardiovascular Disease in Patients three individual BP-lowering drugs, with or without . with : the Cardiovascular . Curr 2) Higher LDL cholesterol-lowering in the ‘Polycap’ group than the groups Hypertens Rep. 2016 Apr;18(5):40. without Simvastatin. 3. James PA, Oparil S, et al. 2014 evidence-based guideline for the management of high 3) Similar reductions in 11-dehydrothromboxane B2 with ‘Polycap’ as in adults: report from the panel members appointed INTRODUCTION to the Eighth Joint National Committee (JNC 8). compared to the three blood-pressure-lowering drugs plus aspirin and JAMA. 2014 Feb 5;311(5):507-20. Dr. Jagdish S. Hiremath aspirin alone. 4. Filipovský J, Widimský Jr J, et al. Summary of 2013 DM, DNB (Cardiology) ESH/ESC Guidelines for the management of arterial n India today, cardiovascular diseases are emerging Interventional Cardiologist Meta analysis of three studies2: hypertension. Prepared by the Czech Society of Hypertension/Czech Society of Cardiology. Cor et as a major health concern both among rural and urban Director: Cath. Lab., 1) ‘Use of a Multidrug Pill In Reducing cardiovascular Events’ (UMPIRE) trial I vasa. 2014;56(e506):e494-e518. population. There has been a phenomenal increase of 59% in Ruby Hall Clinic, Pune 2) ‘IMProving Adherence using Combination Therapy’ (IMPACT) trial 5. Bansilal S, Castellano JM, et al. Global burden of the mortality rates due to coronary vascular disease (CVD) in CVD: focus on secondary prevention of cardiovascular 1 3) ‘Kanyini-Guidelines Adherence with the Polypill’ (GAP) trial disease. Int J Cardiol. 2015 Dec;201 Suppl 1:S1-7. India over the past decade. 6. Barreto M da S, Reiners AAO, et al. Knowledge about Result hypertension and factors associated with the non- There are various risk factors for cardiovascular disease such As compared to conventional regimen, Polypill recipients showed: adherence to drug therapy. Rev Lat Am Enfermagem. as hypertension, dyslipidemia, and insulin resistance. 2014 May-Jun; 22(3): 491-498. 1) Higher adherence (relative risk 1.58; 95% CI 1.32 to 1.90) These risk factors tend to co-exist making an individual prone to the development of cardiovascular disease. Among these risk 7. Kolandaivelu K, Leiden BB, et al. Non-adherence to factors, hypertension is a major, if not the most important, contributor to the disease burden and premature death which is due to 2) 2.5 mmHg (95% CI 0.4 to 4.5) lower systolic BP cardiovascular medications. Eur Heart J. 2014 Dec 7;35(46):3267-76. cardiovascular diseases. Thus, early aggressive lowering of blood pressure is one of the key strategies that is undertaken in order 3) 0.1 mmol/L (95% CI 0.0 to 0.2) lower LDL cholesterol 8. Desgraz B, Collet T-H, et al. Comparison of self- to prevent cardiovascular events like and .2 perceived cardiovascular disease risk among smokers with Framingham and PROCAM scores: a cross- Among the guideline based strategies, combination of more than one anti-hypertensive agents in patients who fail to achieve target sectional analysis of baseline data from a randomised controlled trial. BMJ Open. 2017; 7(1): e012063. blood pressure (BP) within one month of treatment forms one of the key recommendation. Combination therapies lead to physiological ‰‰ Cost reduction: As one pill can uncontrolled hypertension, received 9. Yusuf S. Two decades of progress in preventing and pharmacological synergies between different classes of agents thus imparting greater efficacy and reducing side-effects that may replace multiple pills overall cost of ‘Polycap’ which provided effective vascular disease. Lancet. 2002 Jul 6;360(9326):2-3. occur due to increased dose of a single class of drug.3,4 therapy also decreases. hypertension management and primary 10. Wald NJ, Law MR. A strategy to reduce cardiovascular prevention. This was largely due the fact disease by more than 80%. BMJ. 2003 Jun Apart from BP lowering drugs, anti-platelet drugs like aspirin and cholesterol-lowering therapies like statins also find a place in Polypill administration along with 28;326(7404):1419. strategies to prevent cardiovascular events.2 Overwhelming data from clinical trials show that pharmacologic interventions with that ‘Polycap’ improved his compliance 11. Lonn E, Bosch J, et al. The polypill in the prevention of lifestyle advice can play a potential role 5 to medication as his regimen was now cardiovascular diseases: key concepts, current status, aspirin, statins and BP-lowering agents considerably reduce the risk of vascular events and total mortality. in CVD prevention in a larger number of challenges, and future directions. Circulation. 2010 simple. Apart from this, the patient However, in actual clinical practices, there exists large treatment gaps in appropriate prevention of CVD as a result of which a large at-risk individuals. Nov 16;122(20):2078-88. received appropriate education about his 12. Indian Polycap Study (TIPS), Yusuf S, et al. Effects of number of patients are undetected or under controlled. Some of the reasons may be a lack of a systematic approach to screening condition and therapy along with advice a polypill (Polycap) on risk factors in middle-aged of the adult population, the use of simple, low-cost and effective BP-lowering therapies and lack of patient education. Apart from individuals without cardiovascular disease (TIPS): a Conclusion on lifestyle modification which led to an 5,6 phase II, double-blind, randomised trial. Lancet. 2009 this, non-adherence to cardiovascular medications is another major reason for the apparent discrepancy in CVD control. In the current case, patient who had overall improved response to therapy. Apr 18;373(9672):1341-51. Non adherence to cardiovascular medications can lead to major consequences like increase in cardiovascular events and mortality. In the Reduction of Atherothrombosis for Continued Health (REACH) registry spanning 44 countries, risk of cardiovascular death, myocardial infarction or stroke increased from 13.4 to 17.4% for patients non-adherent at baseline, being even worse in patients For the use of a Registered Medical Practitioner or Hospital LaboratoryFor only. who went from taking to not taking medications at 1 year.7 Non-adherence to cardiovascular strategies could be due to the fact Eligible patients for polypill: that there are multiple drugs required for appropriate control which ‰‰ Hypertensive patients with high CV risk. makes the regimen complex.6 Published in ‰‰ Patients requiring multiple drugs but likely It is thus important to simplify the therapeutic regimen in order to to be non-adherent/non compliant due to increase adherence to drug therapy. One of the strategies to simplify many pills. the regimen would be use of a single pill which is a combination of the essential drugs classes. Such a pill can impart potential synergistic ‰‰ Patients reporting inconvenience due to actions and improve patients’ adherence to medication by reducing complex multiple drug dosing schedules. pill burden and dosing frequency.2 PIF No. : 026/MS/02/17 : PIF No.

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Insights from Clinical Practice Insights from Clinical Practice

Treatment and follow up Results of other assessments BP and imparting primary prevention. Apart from this, ‘Polycap’ also improved CASE: MANAGEMENT OF HIGH RISK PATIENT Patient had a 10-year risk for coronary at 12 weeks (Table 6) the lipid profile of the patient. The patient heart disease as per Framingham Point The patient lost around 2 kg of weight benefited from the lifestyle modification WITH CORONARY VASCULAR DISEASE (CVD) Scores of 18 equivalent to ≥ 30% risk. which could be attributed to lifestyle advice which led to apparent weight The aim of the consulting physician was modifications which he incorporated. loss in 12 weeks time. In the long term, to ensure primary prevention of an event ‘Polycap’ administration and lifestyle He was also on atorvastatin 10 mg Laboratory examination (Table 4) as the patient was found to be at a higher Case Table 6 Results of assessments modifications will definitively change the for lipid management. However, with The patient’s blood pressure was not risk as per Framingham Risk Score. This is a case of a 59-year-old man with patient’s hypertension status and is also number of tablets increasing, he often under control. Laboratory examinations Name of the Result uncontrolled hypertension. The consulting physician also aimed to likely to improve his body mass index avoided taking additional statin tablet revealed dyslipidemia. assessment simplify the treatment regimen of the (BMI) and high-density lipoprotein (HDL) daily. The patient also complained of patient in order to improve the patient’s Lipid profile LDL: 135 mg/dL status. Patient profile chest discomfort while climbing stairs Results of laboratory Triglycerides: 145 mg/dL Table 4 compliance to the medication. ‰‰ A busy executive with a stressful job or physical exertion occasionally. examination HDL: 35 mg/dL profile Name of the Result In India, various combinations of Heart rate 60 beats/minute ‘Polycap’: Polypill concept The Framingham Risk Score of the patient ‰‰ Job involves extensive travel examination antihypertensives are available. However, A hypothesis by Yusuf et al,9 suggested as assessed by the physician during one LDL: Low-density lipoprotein; HDL: High-density Lipid Profile LDL: 160 mg/dL ‘Polycap’ is the only combination with 5 lipoprotein. that combination of 4 drugs [aspirin, a ‰‰ Irregular food and sleep of the routine visits as shown in Table 1. Triglycerides: 155 mg/dL components including aspirin, a statin β-blocker, a statin and an angiotensin- HDL: 34 mg/dL ‰‰ Obese As the patient had more than one and 3 anti-hypertensives. Discussion converting enzyme (ACE) inhibitor] HbA1c 6% cardiovascular risk factor and a high The patient was prescribed ‘Polycap’ This was a case of uncontrolled could reduce CVD events by 75% in Patient history Framingham Risk Score, he was also Serum creatinine 0.9 mg/dL which is a polypill including the following hypertension which occurred due to non- those with vascular disease. Wald and Law10 proposed a concept of polypill ‰‰ Hypertension for 15 years initiated on aspirin. LDL: Low-density lipoprotein; HDL: High-density combination: adherence to anti-hypertensive regimen. lipoprotein. containing 3 BP lowering drugs from ‰‰ Cigarette of ≈200 packs/ His daily medication regimen is 1) 50 mg Patient in the current case showed risk different classes each at half doses, year since 5 years presented in Table 2: Discussion with patient 2) Simvastatin 20 mg factors for cardiovascular disease such as aspirin, a statin and folic acid. Such a ‰‰ Dyslipidemia hypertension, dyslipidemia and obesity polypill was estimated to safely reduce Consulting physician interviewed the 3) 5 mg and thus was on a high probability to ischemic heart disease (IHD) events by The patient had been initiated on Table 2 Daily medication regimen patient about his medication patterns. 4) 12.5 mg develop cardiovascular disease. Patient 88% and by 80% in individuals atenolol 25 mg when he was first The patient felt that his treatment 5) Aspirin 100 mg as (Enteric coated) had a Framingham Point Score of 18 with established CVD and all those older diagnosed and subsequently his dose Name of the drug Course regimen was complex because of multiple The patient also received a equivalent to ≥ 30% risk. Prediction than 55 years without CVD. was increased to 50 mg once a day Atenolol 50 mg OD medications and different schedules. The comprehensive education about his scores such as Framingham Scores have (OD). Despite this, his BP was not Ramipril 5 mg OD apparent discrepancies were discussed Polypill can play a major role in primary overall condition and also about the been developed to estimate the 10- controlled and he was therefore treated in detail with the patient who finally prevention as it could intervene Atorvastatin 10 mg OD year CVD risk. These prediction models with ramipril 2.5 mg OD two years ago. medication administered. Lifestyle simultaneously on several common risk admitted a previous inconsistent intake are increasingly used to identify high- The dose of ramipril was later increased Aspirin 75 mg OD modification advice on diet and exercise factors and theoretically reduce CVD to of the anti-hypertensive drugs. He had risk patients who would benefit from to 5 mg OD for optimal BP control. OD: Once a day. was also imparted to the patient. a large extent.11 a busy office schedule which involved interventions on one or several risk frequent outstation travel which led to Follow-up at 10 days, 4, 8 and 12 weeks factors.8 The patient was prescribed Polypill provides the following Estimation of 10-year risk frequent missing of doses especially day revealed significant reduction in chest Assessment during follow up a complex regimen comprising of advantages in CVD:2 Table 1 for coronary heart disease time doses. Work pressure at office and a pain. BP monitoring revealed that there Tables 3 and 4 present the results of the anti-hypertensive drugs, a statin and Framingham Point Scores busy schedule did not permit a healthier was a significant reduction in BP in the ‰‰ Simplify the treatment regimen as a follow up evaluation of the patient. antiplatelet drugs which was required Criteria Result Score (10- lifestyle. single pill combining multiple drugs follow-up visits (Table 5). for an appropriate primary prevention year risk) can replace complex algorithms. Patient was explained the importance approach. However, use of a multi-drug Age 59 8 Physical examination (Table 3) Sequential reduction of his high-risk status. Also, he was regimen for primary prevention led to ‰‰ Increase the ease of prescription. Total 225 mg/dL 3 Table 5 in BP after ‘Polycap’ cholesterol Results of physical explained the need to take medicines administration non-compliance to medication. ‰‰ Avoid multiple steps for dose Table 3 regularly to minimize risk of future Smoking Smoker and 3 examination Number of the Results of BP Switching to ‘Polycap’ which was a titration of each drug thus benefiting complications. age 59 Parameter Result visit monitoring systolic/ combination of three anti-hypertensive more at-risk individuals. HDL Less than 40 2 diastolic (in mmHg) Pulse rate 68 beats/minute drugs, a lipid lowering drug and an ‰‰ Improve adherence as individuals mg/dL Diagnosis Visit 1 (4 weeks) 148/94 anti-platelet was the strategy applied to would need to take only one Systolic BP 150 mmHg 2 Blood pressure 150/95 mmHg Uncontrolled hypertension due to non- Visit 2 (8 weeks) 142/92 manage the patient. ‘Polycap’ was easy versus several pills per day for CVD Total score 18 ≥ 30% BMI 35 kg/m2 (obese) adherence to anti-hypertensive regimen, Visit 3 (12 weeks) 140/90 for the patient to adhere to and resulted prevention, which may enhance HDL: High-density lipoprotein; BP: Blood pressure. BMI: Body mass index. with high CV risk. BP: Blood pressure. in excellent response in terms of lowering adherence.

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