The use of the CNIC-Polypill in real-life clinical practice: opportunities and challenges in patients at very high risk of atherosclerotic cardiovascular disease - expert panel meeting report

Abstract

Although the cardiovascular (CV) polypill concept is not new and several guidelines state that a CV polypill should be considered an integral part of a comprehensive CV disease (CVD) prevention strategy, there are still some barriers to its implementation in the real-world setting, mainly in secondary CV prevention. As the CNIC-polypill is the only one approved for secondary CV prevention in patients with atherosclerotic CVD in 27 countries worldwide, a panel of four discussants and 30 participants from 18 countries conveyed in a virtual meeting on April 21, 2022, to discuss key clinical questions regarding the practical use of the CNIC-Polypill and barriers to its implementation.Data presented showed that, although the use of the CV polypill is not explicitly mentioned in the current 2021 European Society of Cardiology guidelines on CVD prevention, it may be used in any patient for secondary CVD prevention tolerating all their components to improve outcomes through different aspects. The favourable results of the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial now reinforce this recommendation. The panellists presented algorithms on how to switch from any baseline regimen when starting treatment with the CNIC-polypill in different situations, including patients with hypertension, dyslipidaemia, and a previous CV event; at discharge after a cardiovascular event; in chronic ischemic conditions; and in cases of polypharmacy. The panellists and expert discussants did agree that available studies conducted so far with the CNIC-polypill demonstrate that it is as efficacious as the monocomponents, equipotent drugs, or other therapies; reduces the risk of experiencing recurrent major CV events; improves medication adherence; reduces health care costs and resources compared to patients treated with loose drugs; and the patients prefer it over the multipill strategy.In conclusion, the data presented by the participants provided the evidence behind the use of the CNIC-polypill to help fulfil the goal of encouraging its adoption by physicians.

Keywords: Cardiovascular disease; Cerebrovascular disease; Fixed-dose combination; Polypill; Secondary prevention.

Fig. 1

Steps for switching from baseline treatment to the CNIC-polypill in secondary prevention of cardiovascular disease in patients treated with multiple drugs/pills for their associated cardiovascular risk factors and comorbidities. ASA, acetylsalicylic acid; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; PCSK9i, proprotein convertase subtilisin-kexin type 9 inhibitor. Source: Coca J Hypertens. 2020;38(10):1890–98 [11]. Reproduced with permission

Fig. 2

Algorithm for using the CNIC-polypill in hypertensive patients at very high risk of cardiovascular disease. AAS, acetylsalicylic acid; ATOR, atorvastatin; BP, blood pressure; CCB, calcium channel blocker; diuretic: hydrochlorothiazide, chlortalidone or indapamide; PCSK9i, proprotein convertase subtilisin-kexin type 9 inhibitor; RAM, ramipril. *Twenty or 40 mg of atorvastatin based on initial and target LDL-cholesterol. If the target is not achieved, ezetimibe/PCSK9i can be added. **Diuretic or CCB depending on patient’s metabolic profile. ^†Low-dose: half standard dose. ^§In patients with heart failure with reduced ejection fraction (HFrEF), the priority is to add spironolactone before using high doses of CCBs. Source: Coca J Hypertens. 2020;38(10):1890–98 [11]. Reproduced with permission

Fig. 3

The algorithm shows the steps and options to switch patients hospitalised for an acute coronary syndrome to the CV polypill strategy. Note: The coloured balls represent the appropriate formulation of the CNIC-Polypill according to the coloured lines of the algorithm. ^†Select P2Y12 inhibitor in addition to the CNIC-Polypill. *Dose adjusted to BP levels, previous ACEI/ARB dose and renal function. **Reassess in 3–4 weeks after discharge and readjust the dosage, consider adding A40 or ezetimibe and/or a PCSK9i. ^$Use only if the patient does not develop side effects to atorvastatin 80 mg (or equivalent doses of another statin). ACEI, angiotensin-converting enzyme inhibitor; ACS, acute coronary syndrome; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; ASA, acetylsalicylic acid; AT, atorvastatin; BB, beta blocker; BP, blood pressure; DAPT, dual platelet therapy; EZE, ezetimibe; FDC, fixed-dose combination; LDL-c, low-density lipoprotein cholesterol; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RAM, ramipril; Tx, treatment. Source: Grigorian-Shamagian et al. Front Cardiovasc Med. 2021;8:663,361 [12]. Reproduced with permission

Fig. 4

Grouping of statins by intensity categories according to the percentage reduction in low-density lipoprotein [21]. *Advice from the MHRA (Medicines and Healthcare products Regulatory Agency): there is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80 mg dose should be considered only in patients with severe hypercholesterolemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks

Fig. 5

The algorithm shows the steps and options to switch patients treated for chronic coronary syndromes to the CNIC-Polypill strategy. Note: The coloured balls represent the appropriate formulation of the CNIC-Polypill according to the coloured lines of the algorithm. *Dose adjusted to BP levels, previous ACEI/ARB dose and renal function. **See above for additional treatment of high LDL-c levels. ^$Use only if the patient does not develop side effects to atorvastatin 80 mg (or equivalent doses of another statin). ^†If the combination is available. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ASA, acetylsalicylic acid; AT, atorvastatin; BP, blood pressure; CCB, calcium channel blocker; CCS, chronic coronary syndrome; EZE, ezetimibe; FDC, fixed-dose combination; LDL-c, low-density lipoprotein cholesterol; PAD, peripheral artery disease; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RAM, ramipril; Tx, treatment. Source: Grigorian-Shamagian et al. Front Cardiovasc Med. 2021;8:663,361 [12]. Reproduced with permission

Fig. 6

The algorithm shows the steps and scenarios to reduce the pill burden with the CNIC-Polypill in patients treated for chronic CVD. Note: *Dose adjusted to previous ACEI/ARB dose and renal function. $Use only if the patient does not develop side effects to atorvastatin 80 mg (or equivalent doses of another statin).^†If the combination is available. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ASA, acetylsalicylic acid; AT, atorvastatin; BP, blood pressure; CCB, calcium channel blocker; CCS, chronic coronary syndrome; EZE, ezetimibe; FDC, fixed-dose combination; LDL-c, low-density lipoprotein cholesterol; PAD, peripheral artery disease; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RAM, ramipril; Tx, treatment. Source: Grigorian-Shamagian et al. Front Cardiovasc Med. 2021;8:663,361 [12]. Reproduced with permission

Fig. 7

Summary of the adequate profile of patients considered candidates to switch to the CNIC-Polypill. Note: *Or equivalent doses of the monocomponents. ^$Use only if the patient does not develop side effects to atorvastatin 80 mg (or equivalent doses of another statin). ACS, acute coronary syndrome; AT, atorvastatin; CV, cardiovascular; EZE, ezetimibe; FDC, fixed-dose combination; LDL-c, low-density lipoprotein cholesterol; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor. Source: Adapted from Grigorian-Shamagian et al. Front Cardiovasc Med. 2021;8:663,361 [12] with permission

Fig. 8

Summary of the survey results for each of the clinical statements voted by the participating physicians. ACEi, angiotensin-converting enzyme; CVRF, Cardiovascular risk factors; FDC, fixed-dose combination; HT, hypertension; LDL-c, low density lipoprotein cholesterol; MACE, major adverse cardiovascular event