Servier Slideshow Material

1. COMBINATION FOR YOUR PATIENTS
THE WINNING CARDIOPROTECTIVE

2. The first and only
single-pill combination of
a β-blocker & an ACE
inhibitor
*SmPC COSYREL

3. 1. EUROPA Study Investigators. Lancet. 2003;362:782-788, 2. PROGRESS Collaborative Group. European Heart Journal (2003) 24, 475–484, 3. Patel A. Advance Collaborative Group. Lancet. 2007 Sep 8;370(9590):829-40. 4. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II).
Lancet. 1999; 353(9146):9-13, 5.Von Arnim T. For TIBBS Investigators Journal of American College of Cardiology. 1996; 28(1):20-4.
bisoprolol
All-Cause Mortality
34% RRR (HR: 0.66, 95% CI 0.54-0.81,
p<0.0001)
CIBIS-II
The Cardiac Insufficiency Bisoprolol Study II
TIBBS
Total Ischemic Burden Bisoprolol Study
Event Rate (CV Death, Non-CV Death, MI,
Hospital Admission, CABG, PTCA) 14.8% ARR
(17.5% vs 32.3%, p=0·008)
Unique combination of bisoprolol and perindopril
Primary Endpoint (CV Death, MI, or Cardiac Arrest) 20% RRR (95% CI 9–29, p=0·0003)
Major Coronary Events (Non-Fatal MI, Death due to CHD) Risk Reduction: 26% (95% CI: 6–42%, p0.02)
Death from Cardiovascular Disease. 18% RRR (HR: 0.82, 95% CI 0.68-0.98, p=0.03)
Perindopril proven to reduce major cardiovascular
events

4. Perindopril better than other RAAS blocker, highest T/P ratio
1. SmPC COSYREL, 2. Flack JM. Vasc Health Risk Manag. 2011:7:777-787 (ACE inhibitors) , 3. Song JC et al. Formulary. 2001:36:487-499 (Angiotensin Receptor Blockers), 4. Morris CJ et al. Prog Brain Res. 2012;199:337-
358.
08.00 Noon 16.00 20.00 Midnight 04.00 09.00
0% 20% 40% 60% 80% 100%
Ramipril2
Enalapril2
Lisinopril2
Valsartan3
Losartan3
Olmesartan3
Irbersartan3
50-63%
40-64%
30-70%
69-76%
58-78%
57-70%
60%
87-100%
HIGH-RISK
PERIOD
FOR MI
OR STROKE4
Perindopril1
80%
Candesartan3

5. Proven cardioprotection with COSYREL®
Brugts JJ et. al. Cardovasc Drugs Ther. 2017;31:391-400.Retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29 463 patients with vascular disease.
Multivariate Cox regression analyses were performed patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background β-blocker treatment (11 418 patients received a β-blocker and
5 838 of them had hypertension).
Event-protective effect of perindopril-based regimen
combined with β-blockers in hypertensive patients
Relative Risk
Reduction
N: 29,463 patients
-23%
-26%
-32%
-35%
Primary Endpoint
Non-fatal
MI
All-cause
Mortality
CV
Mortality
(composite of CV mortality,
nonfatal MI, and stroke)

6. 1. Brugts JJ et. al. Cardovasc Drugs Ther. 2017;31:391-400 , 2. Boytsov, S.A., et al. The STYLE Study. Adv Ther (2021). *SmPC COSYREL
One tablet daily to improve adherence2
Unique combination providing long-term CV protection2
Powerful 24-hour blood pressure control1
The first and only single-pill combination
of a β-blocker & an ACE inhibitor

7. COMPOSITION*: Cosyrel 5 mg/5 mg, 5 mg/10 m film-coated tablets contain 5 mg bisoprolol fumarate (bis)/5 mg perindopril arginine (per), 5 mg bis/10 mg per. INDICATIONS*: Cosyrel is indicated as substitution therapy for treatment of hypertension and/or stable coronary artery disease (in
patients with a history of myocardial infarction and/or revascularisation) and/or stable chronic heart failure with reduced systolic left ventricular function (Cosyrel 5 mg/5 mg only) in adult patients adequately controlled with bisoprolol and perindopril given concurrently at the same dose level.
DOSAGE AND ADMINISTRATION*: The usual posology is one tablet once daily. Patients should be stabilized with bisoprolol and perindopril at the same dose level for at least 4 weeks. The fixed dose combination is not suitable for initial therapy. If a change of posology is required, titration
should be done with the individual components. Renal impairment: Cosyrel is not suitable for patients with renal impairment. Individual dose titration with the monocomponent is recommended. Hepatic impairment: no dosage adjustment. Elder-ly: administration according to the renal function.
Paediatric population: safety and efficacy have not been established. Use is not recommended CONTRAINDICATIONS*: Hypersensitivity to the active sub-stances, or to any of the excipients, or to any other ACE inhibitor; acute heart failure or during episodes of heart failure decompensation
requiring i.v. inotropic therapy; cardiogenic shock; second or third degree AV block (without pacemaker); sick sinus syndrome; sinoatrial block; symptomatic bradycardia; symptomatic hypotension; severe bronchial asthma or severe chronic obstructive pulmonary disease; severe forms of
peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome; untreated phaeochromocytoma (see section WARNINGS*); metabolic acidosis; history of angioedema associated with previous ACE inhibitor therapy; hereditary or idiopathic angioedema; second and third
trimesters of pregnancy (see sections WARNINGS*, PREGNANCY* and BREASTFEEDING*); concomitant use with ali-skiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²) (see sections WARNINGS*, INTERACTIONS* and
Pharmacodynamic properties*) concomitant use with sacubitril/valsartan (see WARNING* and INTERACTIONS*), extracorporeal treatments leading to contact of blood with negatively charged surfaces (see INTERACTIONS*), significant bilateral renal artery steno-sis or stenosis of the artery
to a single functioning kidney (see WARNING*).WARNINGS*: Hypotension: initiation should be closely monitored in patients who have been volume depleted, who have severe renin-dependent hypertension, with symptomatic heart failure, with or without associated renal insufficiency, with
ischaemic heart or cerebrovascular disease. A transient hypotensive response is not a con-traindication to further doses once the blood pressure has increased after volume expansion. Hypersensitivity/Angioedema/Intestinal angioedema: stop treatment and monitor until complete resolution
of symptoms. Therapy with beta-blocker must be continued. Angioedema associated with laryngeal oedema may be fatal. Combination with sacubitril/valsartan (contraindicated due to the increased risk of an-gioedema). Sacubitril/valsartan must not be initiated until 36 hours after taking the
last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/val-sartan. Concomitant use of other NEP inhibitors (e.g. racecadotril) and ACE inhibitors may also increase the risk of angioedema. Patients taking concomitant mTOR
inhibitors (e.g. sirolimus, everolimus, temsirolimus) therapy may be at increased risk for angioedema. Hepatic failure: rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death:
treatment should be discontinued if jaundice or marked elevations of hepatic enzymes. Black people: perindopril may be less effective and cause a higher rate of angioedema than in non-black. Non-productive cough. Hyperkalaemia: frequent monitoring of serum potassium if renal
insufficiency, worsening of renal function, age (>70 years), diabetes mellitus, dehydra-tion, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, drugs associated with increases
in serum potassium. Combination with lithium, potassium sparing drugs, potassium supplements, potassium-containing salt substitutes, calcium antagonists, Class I antiarrhytmic drugs, centrally acting an-tihypertensive drugs: not recommended. Dual blockade of the renin-angiotensin-
aldosterone system (RAAS): concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS is therefore not recommended. ACE-inhibitors
and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Stopping treatment: abrupt cessation should be avoided. The posology should be decreased gradually, using the individual components, ide-ally over a period of two weeks.
Bradycardia: if resting heart rate drops below 50-55 beats/min and symptoms related to bradycardia, dose should be downtitrated using the individual components with an appropriate dose of bisoprolol. Patients with first degree AV block, aortic and mitral valve stenosis, hypertrophic
cardiomyopathy, diabetes, strict fasting: use with caution. Patients with Prinzmetal’s angina: Beta-blockers may increase the number and the duration of angina episodes. Renal impairment: daily dose should be adjusted on creatinine clearance. Monitor potassium and creatinine. In patients
with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, increases in blood urea and serum creatinine have been seen; with renovascular hypertension, increased risk of severe hypotension and renal insufficiency.Renovascular hypertension: increased risk of
hypotension and renal insufficiency in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients with unilateral renal artery
stenosis. Patients with recent kidney transplantation, treated for heart failure with insulin dependent diabetes mellitus (type I), severely impaired renal function, severely impaired hepatic function, restrictive cardiomyopathy, congenital heart disease, haemody-namically significant organic
valvular disease, or myocardial infarction within the last 3 months: no experience. Anaphylactoid reactions: reported in patients dialysed with high flux membranes; during LDL apheresis with dextran sulphate, rarely, patients have experienced life-threatening anaphylactoid reactions,
temporarily withhold therapy prior to each apheresis; during desensitization treatment, when ACE inhibitor temporarily withheld, these reactions have been avoided, but reappeared upon inadvertent rechallenge. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: extreme caution in
patients with collagen vascular disease, immunosuppressant therapy, treated with allopurinol or procainamide, periodic monitor of white blood cell counts advised. Bronchospasm (bronchial asthma, obstructive airways diseases): bronchodilating therapy should be given concomitantly.
Anaesthesia: if it is necessary to withdraw beta-blocker before surgery, this should be done gradually and completed about 48 hours before anaesthesia. Treatment should be dicontinued one day prior to surgery. Psoriasis: carefully balance the benefits/risks. Phaeochromocytoma: bisoprolol
should be given with an alpha-receptor blocker. Thyreo-toxicosis: symptoms may be masked.Primary aldosteronism: use not recommended in patients with primary hyperaldosteronism (not responding to drugs acting through inhibition of the renin-angiotensin system). Pregnancy: stop
treatment. If appropriate, start alternative therapy. Excipients: sodium-free. INTERACTIONS*: Contra-indicated: Aliskiren in diabetic or impaired renal patients, Extracorporeal treatments, Sacubitril/Valsartan.Not recommended: Centrally acting antihypertensives such as clonidine and others
(e.g. methyldopa, moxonidine, rilmenidine), Class I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone), Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type, Aliskiren, concomitant therapy with ACE inhibitor and
an-giotensin-receptor blocker, Estramustine, Co-trimoxazole (trimethoprim/sulfamethoxazole), Potassium sparing diuretics (e.g. triamterene, amiloride...), Potassium (salts), Lithium. Requiring special care: Anti-diabetic agents (insulins, oral hypoglycaemic agents), Non-steroidal anti-
inflammatory medicinal products (NSAIDs) (including aspirin ≥ 3 g/day), antihypertensive agents and vasodilators, Tricyclic antidepres-sants/Antipsychotics/Anesthetics, Sympathomimetics, Calcium antagonists of the dihydropyridine type such as felodipine and amlodipine, Class-III
antiarrhythmic drugs (e.g. amiodarone), parasympathomimetic drugs, Topical beta-blockers (e.g. eye drops for glaucoma treatment), Digitalis glycosides, Baclofen, Non-potassium-sparing diuretics, Potassium-sparing diuretics (eplerenone, spirono-lactone), Racecadotril, mTOR inhibitors
(e.g. sirolimus, everolimus, temsirolimus). To be taken into consideration: Mefloquine, Monoamine oxidase inhibitors (except MAO-B inhibitors), Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin), Gold. PREGNANCY AND BREASTFEEDING*: Not recommended during the first trimester
of pregnancy and lactation. Contraindicated during the second and third trimes-ters of pregnancy. FERTILITY*. DRIVE AND USE MACHINES*: Reactions related to low blood pressure may occur in some patients. The ability to drive or operate machinery may be impaired. UNDESIRABLE
EFFECTS*:Very Common: bradycardia. Common: headache, dizziness, vertigo, dysgeusia, paraesthesia, visual impairment, tinnitus, worsening of heart failure, hypotension and effects related to hypotension, feeling of coldness or numbness in the extremities, cough, dyspnoea, abdominal
pain, constipation, diarrhoea, nausea, vomiting, dyspepsia, rash, pruritus, muscle cramps, asthenia, fatigue. Uncommon: eo-sinophilia, hypoglycaemia, hyperkalaemia, hyponatraemia, mood altered, sleep disorder, depression, somnolence, syncope, palpitations, tachycardia, AV-conduction
disturbances, orthostatic hypotension, vasculitis, bronchospasm, dry mouth, angioedema of face, extremities, lips, mucous membranes, tongue, glottis and/or larynx, urticaria, photosensitivity reactions, pemphigoid, hyperhidrosis, muscular weakness, arthralgia, myalgia, renal insufficiency,
erectile dysfunction, chest pain, malaise, oedema peripheral, pyrexia, blood urea increased, blood creatinine increased, fall. Rare: rhinitis, nightmares, hallu-cinations, reduced tear flow, hearing disorders, hepatitis either cytolytic or cholestatic, hypersensitivity reactions (itching, flush, rash),
psoriasis aggravation, potency disorders, hepatic enzyme increased, blood bilirubin increased, increased triglycerides. Very rare: agranulocytosis, pancytopenia, leukopenia, neutropenia, thrombocytopenia, haemolytic anaemia in patients with a congenital deficiency of G-6PDH, confusion,
conjunctivitis, arrhythmia, angina pectoris, myocardial infarction and stroke possibly secondary to excessive hypotension in high-risk patients, eosinophilic pneumonia, pancreatitis, erythema mul-tiform, alopecia, beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash,
renal failure acute, haemoglobin decreased and haematocrit decreased. Raynaud’s phenomenon. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be considered as a very rare but possible complication associated with ACE inhibitor therapy. OVERDOSE*.
PROPERTIES*: Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity. Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (ACE). PRESENTATION*: Tablet container of 30
film-coated tablets of Cosyrel 5 mg/5 mg, 5 mg/10 mg Correspondence: PT. Servier Indonesia, Menara Kadin Indonesia lt. 18, Jl. HR. Rasuna Said Blok X-5 Kav. 2-3, Jakarta 12950. www.servier.co.id. NIE: DKI2068601817A1, DKI2068601817B1 * For complete information, please refer to
the Package Insert.
Product Information
SmPC Code: 151220