19 minute read
Single Pill Combination for Chronic Hypertension
Better adherence and better control
The global prevalence of chronic hypertension continues to rise. The main goals of treating hypertension are to ensure good blood pressure control and to prevent hypertension related adverse cardiovascular outcome. It is estimated that >60 per cent of hypertensive patients still have their blood pressure out of optimal control. The European Society of Cardiology guidelines have provided a strong recommendation to start anti -hypertensive medication with single pill combination as a measure to improve adherence and effective blood pressure control.
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Rami Riziq Yousef Abumuaileq, Consultant Cardiologist at Palestinian Medical Services; Associate Editor at BioMed Central; Associate Editor at European Heart Journal- Case Reports
It is estimated that more than 1.4 billion people are suffering from chronic hypertension in the world (two-third of them are living in low- and middle-income countries). Hypertension is still the most common modifiable risk factor for cardiovascular diseases worldwide. No significant improvement in the rates of hypertensive control has been observed over the last decade. Blood pressure control rates are as low as 17 per cent to 31 per cent in patients diagnosed with hypertension in high income countries, control rates are likely worse in low and middle income countries.
High blood pressure is the leading global cause of premature death, being responsible for around 10 million deaths per year. Furthermore, the global prevalence of hypertension of at least 140 mmHg continues to rise. Hypertension also becomes progressively more common with advancing age, with a prevalence of higher than 60 per cent in people 60 years or older. Therefore, as the population ages, it is predicted that the impact of arterial hypertension will rise further, if management is not optimised.
The “Build and Blood Pressure Study”, carried out on almost 5 million adults between 1934 and 1954, published in 1959, showed a strong direct relationship between high blood pressure and risk of clinical complications and death. In the 1960s, these findings were confirmed in a series of reports from the Framingham Heart Study. The first comprehensive guideline for detection, evaluation, and management of high
BP was published in 1977. Since that, a series of Joint Committee guidelines were published to assist the practice community and improve prevention, awareness, treatment, and control of high blood pressure.
According to most international guidelines, including the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) 2018 guidelines for the management of arterial hypertension in adults, aged at least 18 years, hypertension is defined as a systolic blood pressure at least 140 mmHg and/or a diastolic blood pressure at least 90 mmHg. However, in 2017, joint societies in the United States of America, including the American Heart Association (AHA)/American College of Cardiology (ACC) lowered the level at which ‘hypertension should be defined, to at least 130/80 mmHg. This consequently raised the prevalence of patients with hypertension according to this updated definition. The ESC/ ESH noted during the release of their guidelines in 2018 that the majority of patients do not achieve blood pressure less than 140/90 mmHg, and therefore their focus was to improve goal attainment, rather than to lower the definition of blood pressure beyond the traditional definition of hypertension (i.e., blood pressure at least 140/90 mmHg). Normal blood pressure in persons aged less than 65 years according to both guidelines is, however, defined at a similar level, either as blood pressure 120–129/ 80–84 mmHg in ESC 2018 or as less than 120/80 mmHg in AHA 2017. Studies have demonstrated that attainment of ‘normal’ blood pressure reduces the risk of future cardiovascular adverse events. However, goal attainment remains suboptimal worldwide, even using a goal of less than 140/90 mmHg. In the past decade, guidelines provided measures to overcome the challenge of widespread suboptimal blood pressure control. Among these measures, guidelines from the ESC/ ESH stated that the majority of patients with arterial hypertension initiate two antihypertensive agents to reduce blood pressure quickly towards the therapeutic target. Similarly, the 2017 ACC/AHA guidelines also recommend initiation of two antihypertensive therapies for patients having their blood pressure more than 20/10 mmHg above the target.
The 2018 ESC/ESH guidelines identified that poor adherence to treatment and physician clinical inertia (i.e., lack of physician’s plan and action when the patient’s blood pressure is uncontrolled) are common causes of poor BP control. Overall, more than 50 per cent of patients might fail to adhere properly to their prescribed antihypertensive medications. Moreover, it is estimated that after 1 year, approximately 40 per cent of patients with hypertension may stop permanently their initial drug treatment. The relationship between poor adherence and high cardiovascular risk has been widely reported. A recent meta-analysis demonstrates that SPC therapy leads to improved adherence and persistence compared with free individual drug therapy. A recent meta-analysis, involving 18 studies and 13,56188 patients with hypertension showed that patients with poor adherence to antihypertensive medication had a significantly increased risk of stroke events compared to those with good adherence. A very recent meta-analysis of 44 studies has demonstrated that SPC therapy leads to improved adherence, persistence and blood pressure control compared with free individual drug therapy.
Adherence is considered to be multifactorial. To achieve a greater adherence rate; different factors should be taken into account. These factors would include number of drugs used / frequency of daily doses and patient’s beliefs, lifestyle, personality, and comprehension. Several strategies have been proposed to improve adherence to
antihypertensive medications like drug regimen simplification, education and counselling on home blood pressure monitoring, options to reduce costs, and use of allied health professionals and facilities. Single pill combinations (SPCs) therapy is an approach toward regimen simplification strategy. SPCs could offer a number of advantages versus free individual drug combinations given separately, as it may improve tolerability, reduce pill burden, lower medical costs and resource utilisation, reduce physician clinical inertia, and the most important advantage would be to improve patient adherence to medication. So, SPCs would have the potential to significantly improve the overall blood pressure control rates in treated patients.
The ESC/ESH 2018 guidelines strongly recommend the use of a SPC to simplify drug regimen as a strategy to improve antihypertensive treatment adherence. However, 2017 ACC/ AHA guidelines recommend that the initiation of two antihypertensive drugs can be given either as two pills in a free combination or as an SPC therapy. SPC option is still not recommended at all in the National Institute for Health and Care Excellence guidelines.
Of interest, recently the World Health Organization (WHO) has added, for the very first time, a SPC comprising two antihypertensive medications to the WHO Essential Medicines List, thereby acknowledging that the use of SPC is the emerging best practice for safe, effective, rapid, and convenient hypertension control worldwide
The ultimate goal of antihypertensive therapy is good blood pressure control to reduce the risk of stroke, cardiovascular disease, and renal disease.
Achieving good adherence in the long-term is a challenge. Different factors contribute to good adherence. SPCs should be used in combination with other strategies to improve adherence. Patient beliefs and local concepts still remain obstacles to proper adherence in patients with hypertension. Patients often do not feel unwell and ask why it is necessary to continue taking treatment for long time. Doctors should not forget that combating/discussing patients’ beliefs and thoughts during his visits to the clinic could be an effective strategy to improve adherence to antihypertensive treatment. Other strategies to improve adherence and can be used in conjunction with SPCs, are like home blood pressure monitor, reminder pill boxes, integrated care, and patient preference and sharing in decision making.
Really, reducing pill burden would motivate patients to improve their medication adherence and persistence to therapy, which in turn may have resulted in better blood pressure control and reducing cardiovascular outcome at long term. However, physicians might still have some concerns when prescribing SPCs therapies, including risk of treatment duplication, and the limited ability to individually titrate different components of the single pill with the incidence of any adverse event. As such, further clarification of the benefits is needed for healthcare professionals.
Despite that, meta-analyses have demonstrated benefits of SPCs at achieving good adherence and better blood pressure control and the recent guidelines which recommend SPC over freely individual drug combinations. Further studies are still needed to use ambulatory blood pressure monitor and/or home blood pressure monitor to truly determine the effect of SPC therapy on blood pressure control and cardiovascular outcomes compared with free individual combination therapy.
Regarding the cost issue, concerns have been raised like having multiple dosage strengths and logistic problems for pharmacies having to stock the multiple combinations of the same two drugs. Furthermore, in different countries, SPCs are still more expensive than the generic forms of the individual drugs, and the cost of medication is another important determinant of longterm adherence to therapy. Regarding this point, multiple studies showing that SPCs are linked to significant reductions in medical resource utilisation and are cost-effective when compared with free individual combinations. Mainly through reduction of long-term complications and adverse cardiovascular outcome assumed by better adherence and better pressure control by SPC. So, reductions in total medical costs associated with SPCs at long term more than offset the higher drug costs.
Important points to remember:
1. Evidence favours SPCs as initial treatment for hypertension based on advantages of efficiency, adherence, persistence and safety. ESC/ESH
guidelines strongly recommend SPCs over individual free multi daily dose regimen. 2. The 2018 ESC/ ESH guidelines recommend the combination of a drug that blocks the renin-angiotensin system (RAS) with a calcium channel blocker (CCB) or a thiazide/thiazidelike diuretic. For the RAS inhibitor, the choice is between an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). 3. SPCs are going to stay as a preferred approach to treat arterial hypertension. The physicians (cardiologists, family medicine, primary care doctors etc…) should be aware about different components of SPCs forms (advantages and precautions or contraindications) and their different doses available. 4. Importantly, each component of the SPC should have a sufficient duration of action to provide 24-h blood pressure lowering activity to ensure once daily dosing is effective. Furthermore, it would be an advantage if the two components of the dual combination SPC were also available in a triple pill combination, which would facilitate subsequent up-titration of treatment if it will be necessary. SPCs are clearly here to stay, and they offer appropriate firstline anti-hypertensive treatment for the majority of patients, but not for all. 5. While the net clinical benefit supports an initial two-drug therapy, physicians should be vigilant in relation to vulnerable patients and individualise therapy accordingly. In vulnerable patients (e.g., elderly, frail patients) a more cautious or individualised and stepwise approach with a higher emphasis on safety should be implemented. Even though guidelinesdirected medical therapy is the principle of treatment, individualised treatment and expert advice are still needed in areas of uncertainty. 6. In contrast to the 2013 ESH/ ESC hypertension guidelines, the 2018 European guidelines no longer recommend beta-blockers as a general first-line treatment for hypertension. However, beta-blockers are recommended at any treatment step for hypertensive patients with specific indications including heart failure, angina, post-myocardial infarction, atrial fibrillation, or younger women with, or planning, pregnancy. The combination of a beta-blocker with a thiazide diuretic was criticised previously because of the increased risk of developing diabetes. However, combining a beta-blocker with a dihydropyridine CCB is a logical approach in patients for whom betablockers are indicated. 7. The 2018 ESC/ ESH guidelines recommend the combination of CCB and thiazide/thiazide-like diuretic for initial antihypertensive treatment in black patients, and it may be a good choice in other patients with low renin hypertension. Furthermore, both CCBs and diuretics have been recommended individually as preferred treatments for isolated systolic hypertension in the elderly and both drug groups have shown benefits in reduction of cardiovascular events in older patients. The first SPC of CCB and diuretic to become available was the fixed doe combination of indapamide sustained release (SR) 1.5 mg with amlodipine 5 mg, which is effective with once daily dosing. 8. Thiazide-like diuretic outperformed thiazide diuretic in terms of significant reduction in cardiac event and stroke. Based on 19 randomised trials, the recent 2020 International Society of Hypertension guidelines supported the use of thiazide-like diuretic (e.g., indapamide and chlorthalidone) rather than thiazide diuretic (e.g., hydrochlorothiazide). 9. There are several alternative options for two drug combinations in SPCs to use as first-line anti-hypertensive therapy. Individual patient characteristics may help in deciding which one to choose. The SPC of an ARB with a CCB has emerged as a popular choice, despite the lack of evidence from a clinical outcome trial with this combination. The use of this combination is supported by effective reductions in blood pressure, good tolerability, and the benefit of improved drug adherence with a single tablet. 10. During each visit to the clinic, medical doctors should ensure patient's good adherence. Initiate short discussion, explore obstacles towards good adherence and take patient's preferences into consideration. The final aim is to ensure good adherence and good blood pressure control. 11. Always, evaluate the overall cardiovascular risk level/profile of hypertensive patient and take measures for proper control of his major risk factors (e.g., diabetes mellitus, dyslipidaemia, kidney disease, obesity, smoking, sedentary life style, etc…).
AUTHOR BIO
Rami Riziq Yousef Abumuaileq. Consultant Cardiologist (M.D., Ph.D.) at Palestinian Medical Services- Gaza. Doctorate Degree of Cardiology at Cardiology Department of University Hospital of Santiago de Complostela- University of Santiago de Compostela- Spain. Active member of the European Association of Preventive Cardiology. Associate Editor at European Heart Journal- Case Reports (official journal of European Society of Cardiology). Editor at BioMed Central (BMC Cardiovascular Disorders). Expert and recognized reviewer in several highly qualified and official international journals of Cardiology.
Nilesh Shah
Vice President/General Manager Commercial Advanced Sterilization Products
1) Advanced Sterilization Products has a long history of planning and conveying innovative infection prevention solutions. How do you think this would raise the level of healthcare and safety?
Every day, millions of people around the world visit a healthcare facility. It may be a mother giving birth, a grandfather receiving routine treatment, or a parent visiting a sick child. What they all have in common is a desire to leave the hospital as healthy or healthier than when they arrived. The care and handling of instruments used to treat patients is vital to their health outcome and there is no room for error. But sadly, hundreds of millions of patients are affected by healthcare-associated infections worldwide each year, leading to significant mortality and financial losses for health systems1. And COVID-19 only exacerbated an existing sterilisation and disinfection problem, with a recent poll indicating nearly 80 per cent of responders spend over 75 per cent of their time on COVID-19 infection prevention efforts2 .
1 WHO, Health care-associated infections fact sheet, www.who.int/gpsc/country_work/ gpsc_ccisc_fact_sheet_en.pdf 2 Stevens MP, et al. Impact of COVID-19 on traditional healthcare-associated infection prevention effort. Infect Control Hosp Epidemiol 2020. Apr 16, doi: 10.1017/ ice.2020.141
At Advanced Sterilization Products (ASP), we are dedicated to designing and delivering innovative infection prevention technologies to protect patients during their most critical moments.
In addition to healthcare professionals, we work with additional bodies in Asia Pacific that support the prevention of hospitalacquired infections, to work towards better access and reduced infection-related burdens. For example, in Hong Kong, we partner with the Hong Kong Sterile Supplies Management Association and Infection Control Nurses’ Association to organise conferences and educational seminars.
2) Could you tell our readers how the medical equipment is processed in Advanced Sterilization Products Systems?
Sterilisation offers the greatest margin of safety to device reprocessing, yet conventional high-temperature methods such as steam are not suitable for all devices. The materials that comprise some advanced surgical instruments, and their complex design, necessitates the use of Low-temperature Sterilisation (LTS) to maintain device integrity.
The STERRAD® by ASP exploits the synergism between hydrogen peroxide and low temperature gas plasma (an excited or ionised gas) to rapidly destroy microorganisms. At the completion of the sterilisation process based on this technology, no toxic residues remain on the sterilised items3 .
3) With the best technology available, how would you simplify buying and operating infection prevention products and services for medical facilities globally?
ASP offers the ASP ACCESS® Technology – an informationsharing technology that empowers an ecosystem across ASP devices. It is designed to enhance compliance, automating the documentation of the sterile process, and integrate with leading Instrument Tracking Systems. This greatly improves efficiency as it enables real-time access to sterilisation records that can be used within different departments in a healthcare institution.
4) Can you throw some light on STERRAD® Systems and how they are useful to the current situation prevailing today?
Busy medical facilities need to maintain stringent sterilisation protocols and the current pandemic placed people and resources under extra pressure across the health systems. COVID-19 also caused numerous product shortages and delay in supply chains in the beginning, and possibly affected medical device sterilisation between patients.
When facilities and operators are overwhelmed, there is a risk that they may feel rushed to return medical devices to service with an elevated possibility of skipping or forgetting steps necessary for complete sterilisation. Similarly, issues may arise if people do not have enough resources to engage in the proper sterilisation protocols.
Hence, the pandemic spotlighted the need for sustainable solutions for disinfection needs with shorter turnaround times.
STERRAD® Sterilisation Systems enable faster instrument turnover, as they do not require lengthy aeration and offer a rapid sterilisation cycle (24–60 minutes), saving time and increasing efficiency. This means that instruments can be re-used much sooner, alleviating the costs associated with holding a large number of instrument sets in inventory.
STERRAD® Sterilisation Systems rapidly and safely sterilise medical devices and materials, avoiding exposing users and patients to unnecessary health risks by utilising a combination of H2O2, which is non-carcinogenic, and gas plasma, which eliminates H2O2 residues to leave only water and oxygen. With no toxic emissions or byproducts result, because hydrogen peroxide breaks down to water, STERRAD® avoids the need for expensive abatement systems, and adherence to strict regulatory guidelines associated with preventing and detecting exposure, such as for EtO and FO.
5) With the COVID-19 pandemic affecting millions of people around the world, what role does Advanced Sterilization Products have in protecting patients and healthcare workers?
ASP is committed to protecting patients and healthcare workers with infection prevention solutions. Our products are highly involved in disinfection & sterilisation practices and our teams are doing what is humanly possible, to make them broadly available where needed.
For example, we created an online Coronavirus Resource Center on our website to help our EMEA healthcare communities navigate the significant challenges they are facing in this time of great uncertainty. With important facts and information that is updated, we want to become a resource in combatting COVID-19 and other infections.
Under what the World Health Organisation has called ‘force majeure’, hospitals are looking for solutions outside the ordinary to protect their medical staff and patients. On the quest to find ways to sterilise single use Personal Protective Equipment (PPE) or other materials currently in shortage due to the extreme demand, our STERRAD® low temperature sterilisation systems have been involved in several locally initiated & executed studies.
All sterilisation systems and disinfectant solutions that ASP provides have been tested against enveloped viruses, the family of viruses that includes coronavirus. Furthermore, some of our products, including CIDEX® OPA, have been directly tested against coronavirus, and have been demonstrated to be efficacious.
The pandemic offers huge opportunities to learn lessons for health system preparedness and resilience.
6) What is Advanced Sterilization Products focused on when helping to provide the safest possible environments for patients and healthcare individuals worldwide?
Success of infection prevention and control in health facilities is always due to multiple factors.
ASP has a history of innovation in High Level Disinfection and Low Temperature Sterilisation. ASP developed and introduced CIDEX® OPA to the market over 20 years ago and created the first hydrogen peroxide terminal sterilisation system, STERRAD®.
7) Could you tell which medical device types are at high contamination risk of coronavirus and why?
In a hospital or the course of healthcare set-up, medical devices and instruments will encounter patients infected with coronavirus. To prevent patient-to-patient transfer of the coronavirus, reusable medical devices must be sterilised or thoroughly disinfected between uses.
Devices such as bronchoscopes, ENT flexible endoscopes and laryngoscopes are used for the diagnosis and treatment of patients with advanced coronavirus infections. These devices are reusable and must be disinfected or sterilised between uses. A high number of patients needing advanced care for coronavirus could result in a single device being used multiple times a day.
Medical devices such as blood pressure cuffs, thermometers, monitoring equipment and ventilators, which are used at the bedside will also need to be disinfected or sterilised between uses.
8) How is Advanced Sterilization Products partnering with global regulators, logistics professionals and healthcare providers to expedite products to the field?
ASP is actively working with regulators and healthcare providers across the world to provide products that can aid in reducing or preventing the spread of infection.
In 2020, to mitigate the impact of the COVID-19 pandemic, the Chinese FDA announced it would have a temporary program in place to fast-track devices that assisted in the fight against COVID-19. We were able to satisfy the requirements to bring the AEROFLEX™ Automatic Endoscope Reprocessor (AER) to market early. The AEROFLEX AER has a built-in function to check minimum concentration levels of solution prior to every scope being processed.
9) Which product of Advanced Sterilization Products as per you is effective against Coronavirus and its significance?
Although ASP has not specifically conducted testing of CIDEX® OPA Solution against 2019-nCoV, CIDEX® OPA Solution has been tested for efficacy against human coronavirus. Testing was performed using the United States EPA Virucide Assay Method. Testing was also completed using a diluted strength CIDEX® OPA formulation to present adequate challenge to CIDEX® OPA. The results showed that even at a diluted concentration, CIDEX® OPA Solution inactivates Human Coronavirus.
Additionally, coronaviruses such as SARS-CoV 2 are lipid viruses (enveloped viruses). Lipid viruses are typically, susceptible to various low and medium disinfection modalities according to the guide of the hierarchy of biocide resistance published by the Centers for Disease Control and Prevention (CDC).
Nilesh Shah is the Vice President/General Manager Commercial of Advanced Sterilization Products and is responsible for growth worldwide. Nilesh brings over 20 years of global experience in P&L management, marketing, new business model innovation, engineering and product management. Nilesh has a strong track record of global leadership in the healthcare industry.
AUTHOR BIO
