I am a cardiologist and Director of the Italian Institute of Telemedicine and Chief Researcher at the Scientific Research Department of Cardiology of the First Moscow State Medical University. Our Institute is dedicated to the research and development of new telemedicine solutions for the management of chronic diseases such hypertension, diabetes, asthma, heart failure, and for prevention of cardiovascular diseases. We are also involved in technical and clinical studies based on blood pressure monitoring techniques and various diagnostic tools. Our expertise also extends to the management of clinical and pharmacological trials in different medical specialties. I am member of the Guideline Writing Committee and the Working Group of Blood Pressure Monitoring and Cardiovascular Variability of the Italian and European Society of Hypertension, and member of the Italian, European and International Society of Hypertension, and of the Italian and European Society of Cardiology. I serve as Editor of some scientific journals and I am member of the editorial board of several international journals. I have co-authored hundreds of scientific publications and given lectures in several scientific meetings. Address: Italian Institute of Telemedicine
Via Colombera 29
21048 Solbiate Arno (Varese)
Italy
In their study, Padwal and coworkers tested whether long-term (20 years) home blood pressure tele... more In their study, Padwal and coworkers tested whether long-term (20 years) home blood pressure telemonitoring (BPT) plus pharmacist case management was more cost-effective than usual care in a cohort of high-risk Canadian patients with a recent non-disabling cerebrovascular disease. 1 Authors ran a cost-utility analysis using a Markov decision model applied to a previously published BPT study in a large population of adults with uncontrolled BP followed in a primary care setting under a pharmacist-physician collaborative practice agreement and modified it in order to fit the post-stroke and Canadian context. 2 The baseline characteristics of the cohort were based on a randomized controlled study performed in patients with a recent minor cerebrovascular event. 3 Achieved BP, risk of future cardiovascular (CV) events, attendant consequences on quality-adjusted life years (QALY), and Canadian dollar ($) costs were modeled. BPT was assumed to occur intensively for 3 months, then quarterly. In the base case analysis, the BPT intervention resulted in total costs per patient of 21 640$ and 8.83 QALY, whereas corresponding values for usual care were 23 020$ and 8.00. Home BPT and pharmacist case management resulted in an incremental 0.83 QALY and cost savings of 1929$ compared to usual care. Some sensitivity analyses were run in order to evaluate different scenarios, confirming the intervention dominance even in case the systolic blood pressure (SBP) efficacy was reduced or BPT costs were increased. The authors concluded that the intervention was dominant, achieving improved health at a reduced cost. In the past, few randomized controlled studies based on BPT in hypertensive patients have concluded that the use of technologies may only modestly increase healthcare costs compared to usual care and that the BPT is a cost-effective strategy. Unfortunately, most of these studies suffered from methodological flaws in the economic analysis, were based on a relatively small sample of subjects , short observation periods, and were often performed in mixed populations, including both low-and high-risk patients for which the cost-benefit of the intervention may substantially vary. Evidence on long-term economic benefits of BPT is substantially lacking. In a systematic review of randomized controlled studies that we performed a few years ago, 4 including 6 studies (8 comparisons), the use of BPT was associated with lower medical costs, a finding confirmed in more recent studies 5-7 supporting the cost-effectiveness of this intervention. However, medical costs were offset by those of the equipment and technologies, which contributed to the increase in the overall healthcare costs. The total expenditure was approximately 660 Euros larger in the BPT group than in the usual care group, with a substantial heterogeneity across the studies and a rather broad oscillation of costs (from 640 to 1035 Euros) (Figure). The incremental cost-effectiveness ratio for the healthcare expenditure averaged to nearly 400 Euros for SBP and to nearly 800 Euros for diastolic blood pressure (DBP) over a median follow-up period of 4 years, which means 100-200 Euros per person per year per 1 mmHg of BP reduction. However, when only medical costs were considered, the mean incremental cost-effectiveness ratio dropped to approximately 30 Euros for SBP and 25 Euros for DBP, namely an economically worthwhile intervention. Few of the economic studies published so far specifically evaluated the cost-benefit of pharmacist case management plus BPT. 8-10 These randomized studies were set in outpatient primary care clinics staffed with clinical pharmacy specialists and evaluated direct costs of the intervention on a relatively short time interval (6-12 months).
Community pharmacists play a crucial role in hypertension management and their intervention, main... more Community pharmacists play a crucial role in hypertension management and their intervention, mainly including education, medication monitoring, and reviewing, blood pressure (BP) measurement and cardiovascular risk factors tracking, have proved to enhance BP control and adherence to antihypertensive treatment. A multidisciplinary collaborative approach with the referring physician and a patient-centered model of care have been proved to be particularly effective for improving control of hypertension and promoting patients' health. The inclusion of telehealth in such model (the so-called telepharmacy) may expand the reach of the pharmacist's intervention and provide pharmacy operations and patient care at a distance with further benefits for hypertensive patients and their managing physicians. Very few randomized controlled studies have evaluated the clinical efficacy of the implementation of telepharmacy services in the management of hypertension, with the strongest evidence limited to physician-pharmacist collaborative interventions based on home BP telemonitoring plus patient education on lifestyle, drug therapy, and cardiovascular risk factors control. The results of these trials documented a benefit of telehealth mainly in terms of improvement of BP control consequent to antihypertensive medication intensification and optimization. Although promising, these results need to be corroborated through larger, prospective, and long-term studies, which should also evaluate additional long-term benefits of telepharmacy services in hypertension management.
Telepharmacy is devised to provide pharmacy operations and patient care at a distance and to expa... more Telepharmacy is devised to provide pharmacy operations and patient care at a distance and to expand access to healthcare, enhance patients' safety and improve patient outcomes. A variety of technologies, models of care and interventions are used to develop and provide telepharmacy services, serving diversified populations with different pathological conditions, including cardiovascular diseases. Unfortunately, very few randomized controlled studies have evaluated the clinical efficacy of the implementation of tele-pharmacy services in the management of various cardiovascular conditions, with the strongest evidence being limited to telemonitoring studies in the areas of hypertension and diabetes. Although the clinical efficacy of telepharmacy, and its cost effectiveness, are far from being fully proved, the inclusion of tele-pharmacy services in healthcare models may offer the unique opportunity to increase access to screening and improve care of cardiovascular conditions.
Hypertension and kidney disease often coexist, further increasing the risk of future car-diovascu... more Hypertension and kidney disease often coexist, further increasing the risk of future car-diovascular events. Treatment of hypertensive adults with an angiotensin converting enzyme inhibi-tor in case of concomitant kidney disease may slow disease progression. The third-generation liphophilic angiotensin converting enzyme inhibitor zofenopril, administered alone or combined with a thiazide diuretic, has proved to be effective in lowering blood pressure in hypertensive patients and to reduce the risk of fatal and non-fatal events in post-acute myocardial infarction and heart failure. In almost three-hundred hypertensive patients with kidney impairment zofenopril administered for 12 weeks showed a similar blood pressure-lowering effect irrespective of the stage of the disease, with larger effects in combination with a thiazide diuretic, particularly in patients with slightly or moderately impaired kidney function. In animal models, zofenopril produced a significant and long-lasting inhibition of kidney angiotensin converting enzyme inhibitor and prevented kidney morphological and functional alterations following kidney ischemia-reperfusion injury. Treatment of hypertensive patients for 18 weeks with a combination of zofenopril 30 mg and hy-drochlorothiazide 12.5 mg resulted in a reduction in albumin creatinine ratio of 8.4 mg/g (49.6% reduction from baseline values) and no changes in glomerular filtration rate, variations in line with those obtained in the control group treated with a combination of irbesartan 150 mg and hydro-chlorothiazide 12.5 mg. Thus, some preliminary evidence exists to support that relatively long-term treatment with the angiotensin converting enzyme inhibitor zofenopril alone or combined with hy-drochlorothiazide is effective in controlling blood pressure and may confer some kidney protection due to ACE inhibition properties.
In the last three decades, ischemic heart disease, stroke, and diabetes became leading causes of ... more In the last three decades, ischemic heart disease, stroke, and diabetes became leading causes of mortality and years of life lost (YLL), although with some divergences among countries in the ratio of observed and expected YLLs which is based on sociodemographic indexes. 1 Worldwide, the morbidity and mortality burden associated to cardio-metabolic risk appears to be largely influenced by a rise in blood pressure (BP) levels, body mass index, glucose, and cholesterol. These risk factors are responsible of more than 60% of global death from cardiovascular disease (CVD), chronic kidney disease (CKD), and diabetes, with the high BP having the largest effect. 2 In 2013, high systolic blood pressure (SBP) accounted for 10.4 million deaths and 208.1 million Disability-Adjusted Life Years. 3 People with hypertension (BP ≥140/90 mm Hg or those receiving BP-lowering drugs) have a higher lifetime risk of overall CVD at 30 years of age (63.3% vs 46.1% of those with normal BP) and tend to develop CVD 5.0 years earlier. 4 Even among individuals without known vascular Summary Elevated blood pressure (BP) is a major determinant of morbidity and mortality burden related to cardio-metabolic risk. Current guidelines indicate that controlling and lowering BP promotes cardiovascular (CV) risk reduction. Among antihypertensive agents, angiotensin receptor blockers (ARBs) are characterized by an efficacy profile equivalent to other antihypertensive agents and are provided with excellent tolera-bility and low discontinuation rates during chronic treatments. Moreover, CV outcomes are reduced by ARBs. Olmesartan is a long-lasting ARB which proved to achieve a comparable or more effective action in lowering BP when compared to other ARBs. Olmesartan, in fact, displayed a larger and more sustained antihyperten-sive effect over the 24 hours, with a buffering effect on short-term BP variability. These are important features which differentiate olmesartan from the other principles of the same class and that may help to control the increased CV risk in the presence of high BP variability. Olmesartan shows similar benefits as other ARBs in terms of all-cause and CV mortality, and a favorable tolerability profile. Combination of ol-mesartan with long-lasting calcium-channel blockers and thiazide diuretics represents a rational and effective therapy. Thus, ARBs, including olmesartan, represent one of the most effective and safe treatments for patients with arterial hypertension. K E Y W O R D S ambulatory blood pressure, angiotensin receptor blockers, arterial hypertension, blood pressure, blood pressure variability, olmesartan
Purpose: Hypertension guidelines recommend measuring blood pressure (BP) on both arms, since an a... more Purpose: Hypertension guidelines recommend measuring blood pressure (BP) on both arms, since an abnormal inter-arm difference (IAD) in BP is associated with an increased risk of vascu-lar abnormalities and cardiovascular (CV) disease. We tested whether an automatic oscillometric BP monitor allowing simultaneous both arm BP measurement might be effective for screening of subjects with potential vascular disease. Materials and methods: 220 consecutive subjects from an unselected sample of individuals of a small Italian community were screened using an automated upper-arm electronic BP monitor (Microlife WatchBP Office). Seated BP was measured in triplicate at 1 min interval. Demographic and clinical data were collected prior to any BP measurement. An average IAD difference >20 mmHg for systolic (S) and/or >10 mmHg for diastolic (D) BP was considered abnormal. Results: In 9 subjects (4.1%) an abnormal IAD was found, with lower BPs measured in the non-dominant arm (147 ± 28/78 ± 9 vs. 154 ± 15/92 ± 11 mmHg dominant, p<.01). Subjects with a significant IAD were significantly older (71 ± 8 vs. 57 ± 15 years, p¼.005), had a greater body mass index (BMI: 32 ± 7 vs. 25 ± 4 kg/m 2 , p¼.0001), higher BP levels (154 ± 15/92 ± 11 vs. 133 ± 18/ 80 ± 10 mmHg, p¼.001) and were more likely to report obesity (56 vs. 13%, p¼.001), a history of hypertension (67 vs. 35%, p¼.044) or cardiovascular disease (33 vs. 10%, p¼.034) than subjects with normal IAD. In a multivariate analysis, a higher BMI [odds ratio (95% confidence interval): 1.29 (1.11, 1.51)] and SBP [1.06 (1.01, 1.10)] were significantly associated with a larger risk of an abnormal IAD (p¼.001 and p¼.012, respectively). Conclusions: An abnormal IAD in BP is associated with a larger prevalence of CV risk factors and CV disease. Our study confirms that simultaneous both arm BP measurement must always be accomplished in subjects at risk for or with established CV disease. ARTICLE HISTORY
Blood pressure lowering by all classes of anti-hypertensive drugs is accompanied by significant r... more Blood pressure lowering by all classes of anti-hypertensive drugs is accompanied by significant reductions of stroke and major cardiovascular (CV) events. Drugs acting on the renin-angiotensin-aldosterone system, such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), showed similar benefit on major CV events to other antihypertensive medications. In real-world practice, ARBs reduced by 10% the incidence of CV mortality, non-fatal myocardial infarction, non-fatal stroke and provided superior protection against CV events than ACEIs in high-risk patients. Despite similar antihyper-tensive properties and a favourable safety profile for both ACEIs and ARBs, evidence indicates that patients treated with ARBs have lower rates of withdrawal for adverse events and greater persistence to therapy than those treated with ACEIs. Among ARBs, olmesartan is one of the latest generation compounds introduced in clinical practice for treating hypertension: head-to-head comparative trials suggest that the efficacy of olmesartan is superior to that of commonly prescribed ACEIs (ramipril and perindopril). The drug, administered as a monotherapy or in combination with a dihy-dropyridine calcium channel blocker or a thi-azide diuretic, has proved to be effective in maintaining blood pressure stability over 24 h, with a favourable safety profile and low dis-continuation rates. These properties are pivotal for considering olmesartan as a useful antihy-pertensive agent especially for high-risk patients (e.g. elderly, diabetics, patients with metabolic syndrome). Funding: Article preparation and open access fee were funded by Menarini International Operations Luxembourg S.A. (M.I.O.L.)
BACKGROUND:
In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early ... more BACKGROUND: In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs). METHODS: This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD. RESULTS: Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD-). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD- (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74-1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55-0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46-0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP). CONCLUSION: In post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.
BACKGROUND:
Oxidative stress is increased in hyperuricemic patients with acute myocardial infarct... more BACKGROUND: Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival. OBJECTIVE: We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. METHODS: One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).
RESULTS: MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169]. CONCLUSIONS: Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhib... more Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5 years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure.
Blood pressure telemonitoring (BPT) is a telehealth strategy that allows remote data transmission... more Blood pressure telemonitoring (BPT) is a telehealth strategy that allows remote data transmission of blood pressure and additional information on patients' health status from their dwellings or from a community setting to the doctor's office or the hospital. There is sufficiently strong evidence from several randomized controlled trials that the regular and prolonged use of BPT combined with telecounseling and case management under the supervision of a team of healthcare professionals is associated with a significant blood pressure reduction compared with usual care, particularly in cases of patients at high risk. However, most current evidence is based on studies of relatively short duration (<12 months), and in the few studies that have investigated longer-term outcomes, no evidence of better or sustained effect could be provided. In addition, no definition of the optimal BPT-based healthcare delivery model could be derived from the studies performed so far, because of the heterogeneity of interventions, technologies, and study designs. BPT can also be provided in the context of "mobile health" (m-health) wireless solutions, together with educational support, medication reminders, and teleconsultation. When BPT is integrated in an m-health solution, it has the potential to promote patient's self-management, as a complement to the doctor's intervention, and encourage greater participation in medical decision-making. In conclusion, BPT has a potential key role in the management of patients with hypertension, since it seems to improve the quality of delivered care and allow for more effective prevention of the cardiovascular consequences of hypertension.
Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) a... more Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP.
Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, ea... more Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients. Methods: This was a post-hoc analysis of pooled individual patient data from the four large random-ized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes. Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR ¼ 0.66; and 95% confidence interval, CI ¼ 0.44–0.98; p ¼ .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR ¼ 0.78; 95% CI ¼ 0.63–0.97; p ¼ .026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR ¼ 0.76; 95% CI ¼ 0.61–0.94); p ¼ .013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering. Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1 year.
The pharmacist may play a relevant role in primary and secondary prevention of cardiovascular dis... more The pharmacist may play a relevant role in primary and secondary prevention of cardiovascular diseases, mainly through patient education and counselling, drug safety management, medication review, monitoring and reconciliation, detection and control of specific cardiovascular risk factors (eg, blood pressure, blood glucose, serum lipids) and clinical outcomes. Systematic reviews of randomised controlled and observational studies have documented an improved control of hypertension, dyslipidaemia or diabetes, smoking cessation and reduced hospitalisation in patients with heart failure, following a pharmacist’s intervention. Limited proof for effectiveness is available for humanistic (patient satisfaction, adherence and knowledge) and economic outcomes. A multidisciplinary approach, including medical input plus a pharmacist, specialist nurse or both, and a greater involvement of community rather than hospital pharmacists, seems to represent the most efficient and modern healthcare delivery model. However, further welldesigned research is demanded in order to quantitatively and qualitatively evaluate the impact of pharmacist’s interventions on cardiovascular disease and to identify specific areas of impact of collaborative practice. Such research should particularly focus on the demonstration of a sensitivity to community pharmacist’s intervention. Since pharmacy services are easily accessible and widely distributed in the community setting, a maximum benefit should be expected from interventions provided in this context.
Purpose: The four SMILE studies demonstrated that early administration of zofenopril following ac... more Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angioten-sin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisino-pril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p ¼ .003 and .60, .36–.99; p ¼ .049, respectively) and normotensive patients (0.56, 0.42–0.75; p ¼ .0001 and .51, .28–.90; p ¼ .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p ¼ .918; normotensives: 0.91, 0.59–1.41; p ¼ .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p ¼ .045), but not in normotensive patients (0.77; 0.55–1.10; p ¼ .150). Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.
Background: The metabolic syndrome (MS) is a clustering of different cardiovascular (CV) risk fac... more Background: The metabolic syndrome (MS) is a clustering of different cardiovascular (CV) risk factors, which further enhances the risk of death and CV complications in post-acute myocardial infarction (AMI) patients. In the present meta-analysis of individual data of the four randomized, prospective SMILE studies, we evaluated the efficacy of zofenopril vs. lisinopril, ramipril, and placebo on 1-year CV morbidity and mortality, according to the presence (+) or absence (of of the MS. Methods: 2203 (63.2%) of the 3488 patients were classified as MS+, 1285 (36.8%) as MS-. Five hundred two MS+ and 380 MS-were treated with placebo, 1134 and 608 with zofenopril 30–60 mg/die, 340 and 175 with lisinopril 5–10 mg/die, and 227 and 122 with ramipril 10 mg/die. Treatment was continued for 6 to 48 weeks. Results: The 1-year risk of a major CV event was similar (P = 0.420) in MS+ (18.1%) and MS-(18.0%) patients [HR and 95% confidence interval: 0.92 (0.76–1.12)]. After accounting for MS+/MS-, the 1-year risk of CV events vs. placebo was significantly lower under zofenopril [0.79 (0.63–0.97); P = 0.028] and lisinopril [0.65 (0.47–0.89); P = 0.007], but larger under ramipril [2.57 (1.94–3.93); P = 0.0001]. Treatment with zofe-nopril was associated with a statistically significant (P = 0.0001) reduction in CV risk as compared with the other angiotensin-converting enzyme inhibitors [MS+: 0.52 (0.42–0.66); MS-: 0.52 (0.38–0.73)]. Conclusions: In post-AMI patients with MS, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared with placebo, with an efficacy similar to lisi-nopril, but better than ramipril.
In their study, Padwal and coworkers tested whether long-term (20 years) home blood pressure tele... more In their study, Padwal and coworkers tested whether long-term (20 years) home blood pressure telemonitoring (BPT) plus pharmacist case management was more cost-effective than usual care in a cohort of high-risk Canadian patients with a recent non-disabling cerebrovascular disease. 1 Authors ran a cost-utility analysis using a Markov decision model applied to a previously published BPT study in a large population of adults with uncontrolled BP followed in a primary care setting under a pharmacist-physician collaborative practice agreement and modified it in order to fit the post-stroke and Canadian context. 2 The baseline characteristics of the cohort were based on a randomized controlled study performed in patients with a recent minor cerebrovascular event. 3 Achieved BP, risk of future cardiovascular (CV) events, attendant consequences on quality-adjusted life years (QALY), and Canadian dollar ($) costs were modeled. BPT was assumed to occur intensively for 3 months, then quarterly. In the base case analysis, the BPT intervention resulted in total costs per patient of 21 640$ and 8.83 QALY, whereas corresponding values for usual care were 23 020$ and 8.00. Home BPT and pharmacist case management resulted in an incremental 0.83 QALY and cost savings of 1929$ compared to usual care. Some sensitivity analyses were run in order to evaluate different scenarios, confirming the intervention dominance even in case the systolic blood pressure (SBP) efficacy was reduced or BPT costs were increased. The authors concluded that the intervention was dominant, achieving improved health at a reduced cost. In the past, few randomized controlled studies based on BPT in hypertensive patients have concluded that the use of technologies may only modestly increase healthcare costs compared to usual care and that the BPT is a cost-effective strategy. Unfortunately, most of these studies suffered from methodological flaws in the economic analysis, were based on a relatively small sample of subjects , short observation periods, and were often performed in mixed populations, including both low-and high-risk patients for which the cost-benefit of the intervention may substantially vary. Evidence on long-term economic benefits of BPT is substantially lacking. In a systematic review of randomized controlled studies that we performed a few years ago, 4 including 6 studies (8 comparisons), the use of BPT was associated with lower medical costs, a finding confirmed in more recent studies 5-7 supporting the cost-effectiveness of this intervention. However, medical costs were offset by those of the equipment and technologies, which contributed to the increase in the overall healthcare costs. The total expenditure was approximately 660 Euros larger in the BPT group than in the usual care group, with a substantial heterogeneity across the studies and a rather broad oscillation of costs (from 640 to 1035 Euros) (Figure). The incremental cost-effectiveness ratio for the healthcare expenditure averaged to nearly 400 Euros for SBP and to nearly 800 Euros for diastolic blood pressure (DBP) over a median follow-up period of 4 years, which means 100-200 Euros per person per year per 1 mmHg of BP reduction. However, when only medical costs were considered, the mean incremental cost-effectiveness ratio dropped to approximately 30 Euros for SBP and 25 Euros for DBP, namely an economically worthwhile intervention. Few of the economic studies published so far specifically evaluated the cost-benefit of pharmacist case management plus BPT. 8-10 These randomized studies were set in outpatient primary care clinics staffed with clinical pharmacy specialists and evaluated direct costs of the intervention on a relatively short time interval (6-12 months).
Community pharmacists play a crucial role in hypertension management and their intervention, main... more Community pharmacists play a crucial role in hypertension management and their intervention, mainly including education, medication monitoring, and reviewing, blood pressure (BP) measurement and cardiovascular risk factors tracking, have proved to enhance BP control and adherence to antihypertensive treatment. A multidisciplinary collaborative approach with the referring physician and a patient-centered model of care have been proved to be particularly effective for improving control of hypertension and promoting patients' health. The inclusion of telehealth in such model (the so-called telepharmacy) may expand the reach of the pharmacist's intervention and provide pharmacy operations and patient care at a distance with further benefits for hypertensive patients and their managing physicians. Very few randomized controlled studies have evaluated the clinical efficacy of the implementation of telepharmacy services in the management of hypertension, with the strongest evidence limited to physician-pharmacist collaborative interventions based on home BP telemonitoring plus patient education on lifestyle, drug therapy, and cardiovascular risk factors control. The results of these trials documented a benefit of telehealth mainly in terms of improvement of BP control consequent to antihypertensive medication intensification and optimization. Although promising, these results need to be corroborated through larger, prospective, and long-term studies, which should also evaluate additional long-term benefits of telepharmacy services in hypertension management.
Telepharmacy is devised to provide pharmacy operations and patient care at a distance and to expa... more Telepharmacy is devised to provide pharmacy operations and patient care at a distance and to expand access to healthcare, enhance patients' safety and improve patient outcomes. A variety of technologies, models of care and interventions are used to develop and provide telepharmacy services, serving diversified populations with different pathological conditions, including cardiovascular diseases. Unfortunately, very few randomized controlled studies have evaluated the clinical efficacy of the implementation of tele-pharmacy services in the management of various cardiovascular conditions, with the strongest evidence being limited to telemonitoring studies in the areas of hypertension and diabetes. Although the clinical efficacy of telepharmacy, and its cost effectiveness, are far from being fully proved, the inclusion of tele-pharmacy services in healthcare models may offer the unique opportunity to increase access to screening and improve care of cardiovascular conditions.
Hypertension and kidney disease often coexist, further increasing the risk of future car-diovascu... more Hypertension and kidney disease often coexist, further increasing the risk of future car-diovascular events. Treatment of hypertensive adults with an angiotensin converting enzyme inhibi-tor in case of concomitant kidney disease may slow disease progression. The third-generation liphophilic angiotensin converting enzyme inhibitor zofenopril, administered alone or combined with a thiazide diuretic, has proved to be effective in lowering blood pressure in hypertensive patients and to reduce the risk of fatal and non-fatal events in post-acute myocardial infarction and heart failure. In almost three-hundred hypertensive patients with kidney impairment zofenopril administered for 12 weeks showed a similar blood pressure-lowering effect irrespective of the stage of the disease, with larger effects in combination with a thiazide diuretic, particularly in patients with slightly or moderately impaired kidney function. In animal models, zofenopril produced a significant and long-lasting inhibition of kidney angiotensin converting enzyme inhibitor and prevented kidney morphological and functional alterations following kidney ischemia-reperfusion injury. Treatment of hypertensive patients for 18 weeks with a combination of zofenopril 30 mg and hy-drochlorothiazide 12.5 mg resulted in a reduction in albumin creatinine ratio of 8.4 mg/g (49.6% reduction from baseline values) and no changes in glomerular filtration rate, variations in line with those obtained in the control group treated with a combination of irbesartan 150 mg and hydro-chlorothiazide 12.5 mg. Thus, some preliminary evidence exists to support that relatively long-term treatment with the angiotensin converting enzyme inhibitor zofenopril alone or combined with hy-drochlorothiazide is effective in controlling blood pressure and may confer some kidney protection due to ACE inhibition properties.
In the last three decades, ischemic heart disease, stroke, and diabetes became leading causes of ... more In the last three decades, ischemic heart disease, stroke, and diabetes became leading causes of mortality and years of life lost (YLL), although with some divergences among countries in the ratio of observed and expected YLLs which is based on sociodemographic indexes. 1 Worldwide, the morbidity and mortality burden associated to cardio-metabolic risk appears to be largely influenced by a rise in blood pressure (BP) levels, body mass index, glucose, and cholesterol. These risk factors are responsible of more than 60% of global death from cardiovascular disease (CVD), chronic kidney disease (CKD), and diabetes, with the high BP having the largest effect. 2 In 2013, high systolic blood pressure (SBP) accounted for 10.4 million deaths and 208.1 million Disability-Adjusted Life Years. 3 People with hypertension (BP ≥140/90 mm Hg or those receiving BP-lowering drugs) have a higher lifetime risk of overall CVD at 30 years of age (63.3% vs 46.1% of those with normal BP) and tend to develop CVD 5.0 years earlier. 4 Even among individuals without known vascular Summary Elevated blood pressure (BP) is a major determinant of morbidity and mortality burden related to cardio-metabolic risk. Current guidelines indicate that controlling and lowering BP promotes cardiovascular (CV) risk reduction. Among antihypertensive agents, angiotensin receptor blockers (ARBs) are characterized by an efficacy profile equivalent to other antihypertensive agents and are provided with excellent tolera-bility and low discontinuation rates during chronic treatments. Moreover, CV outcomes are reduced by ARBs. Olmesartan is a long-lasting ARB which proved to achieve a comparable or more effective action in lowering BP when compared to other ARBs. Olmesartan, in fact, displayed a larger and more sustained antihyperten-sive effect over the 24 hours, with a buffering effect on short-term BP variability. These are important features which differentiate olmesartan from the other principles of the same class and that may help to control the increased CV risk in the presence of high BP variability. Olmesartan shows similar benefits as other ARBs in terms of all-cause and CV mortality, and a favorable tolerability profile. Combination of ol-mesartan with long-lasting calcium-channel blockers and thiazide diuretics represents a rational and effective therapy. Thus, ARBs, including olmesartan, represent one of the most effective and safe treatments for patients with arterial hypertension. K E Y W O R D S ambulatory blood pressure, angiotensin receptor blockers, arterial hypertension, blood pressure, blood pressure variability, olmesartan
Purpose: Hypertension guidelines recommend measuring blood pressure (BP) on both arms, since an a... more Purpose: Hypertension guidelines recommend measuring blood pressure (BP) on both arms, since an abnormal inter-arm difference (IAD) in BP is associated with an increased risk of vascu-lar abnormalities and cardiovascular (CV) disease. We tested whether an automatic oscillometric BP monitor allowing simultaneous both arm BP measurement might be effective for screening of subjects with potential vascular disease. Materials and methods: 220 consecutive subjects from an unselected sample of individuals of a small Italian community were screened using an automated upper-arm electronic BP monitor (Microlife WatchBP Office). Seated BP was measured in triplicate at 1 min interval. Demographic and clinical data were collected prior to any BP measurement. An average IAD difference >20 mmHg for systolic (S) and/or >10 mmHg for diastolic (D) BP was considered abnormal. Results: In 9 subjects (4.1%) an abnormal IAD was found, with lower BPs measured in the non-dominant arm (147 ± 28/78 ± 9 vs. 154 ± 15/92 ± 11 mmHg dominant, p<.01). Subjects with a significant IAD were significantly older (71 ± 8 vs. 57 ± 15 years, p¼.005), had a greater body mass index (BMI: 32 ± 7 vs. 25 ± 4 kg/m 2 , p¼.0001), higher BP levels (154 ± 15/92 ± 11 vs. 133 ± 18/ 80 ± 10 mmHg, p¼.001) and were more likely to report obesity (56 vs. 13%, p¼.001), a history of hypertension (67 vs. 35%, p¼.044) or cardiovascular disease (33 vs. 10%, p¼.034) than subjects with normal IAD. In a multivariate analysis, a higher BMI [odds ratio (95% confidence interval): 1.29 (1.11, 1.51)] and SBP [1.06 (1.01, 1.10)] were significantly associated with a larger risk of an abnormal IAD (p¼.001 and p¼.012, respectively). Conclusions: An abnormal IAD in BP is associated with a larger prevalence of CV risk factors and CV disease. Our study confirms that simultaneous both arm BP measurement must always be accomplished in subjects at risk for or with established CV disease. ARTICLE HISTORY
Blood pressure lowering by all classes of anti-hypertensive drugs is accompanied by significant r... more Blood pressure lowering by all classes of anti-hypertensive drugs is accompanied by significant reductions of stroke and major cardiovascular (CV) events. Drugs acting on the renin-angiotensin-aldosterone system, such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), showed similar benefit on major CV events to other antihypertensive medications. In real-world practice, ARBs reduced by 10% the incidence of CV mortality, non-fatal myocardial infarction, non-fatal stroke and provided superior protection against CV events than ACEIs in high-risk patients. Despite similar antihyper-tensive properties and a favourable safety profile for both ACEIs and ARBs, evidence indicates that patients treated with ARBs have lower rates of withdrawal for adverse events and greater persistence to therapy than those treated with ACEIs. Among ARBs, olmesartan is one of the latest generation compounds introduced in clinical practice for treating hypertension: head-to-head comparative trials suggest that the efficacy of olmesartan is superior to that of commonly prescribed ACEIs (ramipril and perindopril). The drug, administered as a monotherapy or in combination with a dihy-dropyridine calcium channel blocker or a thi-azide diuretic, has proved to be effective in maintaining blood pressure stability over 24 h, with a favourable safety profile and low dis-continuation rates. These properties are pivotal for considering olmesartan as a useful antihy-pertensive agent especially for high-risk patients (e.g. elderly, diabetics, patients with metabolic syndrome). Funding: Article preparation and open access fee were funded by Menarini International Operations Luxembourg S.A. (M.I.O.L.)
BACKGROUND:
In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early ... more BACKGROUND: In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs). METHODS: This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD. RESULTS: Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD-). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD- (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74-1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55-0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46-0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP). CONCLUSION: In post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.
BACKGROUND:
Oxidative stress is increased in hyperuricemic patients with acute myocardial infarct... more BACKGROUND: Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival. OBJECTIVE: We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. METHODS: One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).
RESULTS: MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169]. CONCLUSIONS: Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhib... more Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5 years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure.
Blood pressure telemonitoring (BPT) is a telehealth strategy that allows remote data transmission... more Blood pressure telemonitoring (BPT) is a telehealth strategy that allows remote data transmission of blood pressure and additional information on patients' health status from their dwellings or from a community setting to the doctor's office or the hospital. There is sufficiently strong evidence from several randomized controlled trials that the regular and prolonged use of BPT combined with telecounseling and case management under the supervision of a team of healthcare professionals is associated with a significant blood pressure reduction compared with usual care, particularly in cases of patients at high risk. However, most current evidence is based on studies of relatively short duration (<12 months), and in the few studies that have investigated longer-term outcomes, no evidence of better or sustained effect could be provided. In addition, no definition of the optimal BPT-based healthcare delivery model could be derived from the studies performed so far, because of the heterogeneity of interventions, technologies, and study designs. BPT can also be provided in the context of "mobile health" (m-health) wireless solutions, together with educational support, medication reminders, and teleconsultation. When BPT is integrated in an m-health solution, it has the potential to promote patient's self-management, as a complement to the doctor's intervention, and encourage greater participation in medical decision-making. In conclusion, BPT has a potential key role in the management of patients with hypertension, since it seems to improve the quality of delivered care and allow for more effective prevention of the cardiovascular consequences of hypertension.
Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) a... more Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP.
Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, ea... more Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients. Methods: This was a post-hoc analysis of pooled individual patient data from the four large random-ized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes. Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR ¼ 0.66; and 95% confidence interval, CI ¼ 0.44–0.98; p ¼ .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR ¼ 0.78; 95% CI ¼ 0.63–0.97; p ¼ .026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR ¼ 0.76; 95% CI ¼ 0.61–0.94); p ¼ .013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering. Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1 year.
The pharmacist may play a relevant role in primary and secondary prevention of cardiovascular dis... more The pharmacist may play a relevant role in primary and secondary prevention of cardiovascular diseases, mainly through patient education and counselling, drug safety management, medication review, monitoring and reconciliation, detection and control of specific cardiovascular risk factors (eg, blood pressure, blood glucose, serum lipids) and clinical outcomes. Systematic reviews of randomised controlled and observational studies have documented an improved control of hypertension, dyslipidaemia or diabetes, smoking cessation and reduced hospitalisation in patients with heart failure, following a pharmacist’s intervention. Limited proof for effectiveness is available for humanistic (patient satisfaction, adherence and knowledge) and economic outcomes. A multidisciplinary approach, including medical input plus a pharmacist, specialist nurse or both, and a greater involvement of community rather than hospital pharmacists, seems to represent the most efficient and modern healthcare delivery model. However, further welldesigned research is demanded in order to quantitatively and qualitatively evaluate the impact of pharmacist’s interventions on cardiovascular disease and to identify specific areas of impact of collaborative practice. Such research should particularly focus on the demonstration of a sensitivity to community pharmacist’s intervention. Since pharmacy services are easily accessible and widely distributed in the community setting, a maximum benefit should be expected from interventions provided in this context.
Purpose: The four SMILE studies demonstrated that early administration of zofenopril following ac... more Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angioten-sin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisino-pril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p ¼ .003 and .60, .36–.99; p ¼ .049, respectively) and normotensive patients (0.56, 0.42–0.75; p ¼ .0001 and .51, .28–.90; p ¼ .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p ¼ .918; normotensives: 0.91, 0.59–1.41; p ¼ .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p ¼ .045), but not in normotensive patients (0.77; 0.55–1.10; p ¼ .150). Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.
Background: The metabolic syndrome (MS) is a clustering of different cardiovascular (CV) risk fac... more Background: The metabolic syndrome (MS) is a clustering of different cardiovascular (CV) risk factors, which further enhances the risk of death and CV complications in post-acute myocardial infarction (AMI) patients. In the present meta-analysis of individual data of the four randomized, prospective SMILE studies, we evaluated the efficacy of zofenopril vs. lisinopril, ramipril, and placebo on 1-year CV morbidity and mortality, according to the presence (+) or absence (of of the MS. Methods: 2203 (63.2%) of the 3488 patients were classified as MS+, 1285 (36.8%) as MS-. Five hundred two MS+ and 380 MS-were treated with placebo, 1134 and 608 with zofenopril 30–60 mg/die, 340 and 175 with lisinopril 5–10 mg/die, and 227 and 122 with ramipril 10 mg/die. Treatment was continued for 6 to 48 weeks. Results: The 1-year risk of a major CV event was similar (P = 0.420) in MS+ (18.1%) and MS-(18.0%) patients [HR and 95% confidence interval: 0.92 (0.76–1.12)]. After accounting for MS+/MS-, the 1-year risk of CV events vs. placebo was significantly lower under zofenopril [0.79 (0.63–0.97); P = 0.028] and lisinopril [0.65 (0.47–0.89); P = 0.007], but larger under ramipril [2.57 (1.94–3.93); P = 0.0001]. Treatment with zofe-nopril was associated with a statistically significant (P = 0.0001) reduction in CV risk as compared with the other angiotensin-converting enzyme inhibitors [MS+: 0.52 (0.42–0.66); MS-: 0.52 (0.38–0.73)]. Conclusions: In post-AMI patients with MS, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared with placebo, with an efficacy similar to lisi-nopril, but better than ramipril.
Uploads
Papers by Stefano Omboni
In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs).
METHODS:
This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD.
RESULTS:
Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD-). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD- (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74-1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55-0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46-0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP).
CONCLUSION:
In post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.
Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival.
OBJECTIVE:
We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies.
METHODS:
One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).
RESULTS:
MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169].
CONCLUSIONS:
Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
interventions on cardiovascular disease and to identify specific areas of impact of collaborative practice. Such research should particularly focus on the demonstration of a sensitivity to community pharmacist’s intervention. Since pharmacy services are easily accessible and widely
distributed in the community setting, a maximum benefit should be expected from interventions provided in this context.
In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs).
METHODS:
This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD.
RESULTS:
Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD-). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD- (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74-1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55-0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46-0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP).
CONCLUSION:
In post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.
Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival.
OBJECTIVE:
We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies.
METHODS:
One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).
RESULTS:
MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169].
CONCLUSIONS:
Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
interventions on cardiovascular disease and to identify specific areas of impact of collaborative practice. Such research should particularly focus on the demonstration of a sensitivity to community pharmacist’s intervention. Since pharmacy services are easily accessible and widely
distributed in the community setting, a maximum benefit should be expected from interventions provided in this context.