Short-acting Nitrate Consumption Research Articles

Randomised Placebo-Controlled Pilot Trial Evaluating the Anti-Anginal Efficacy of Ticagrelor in Patients with Angina with Nonobstructive Coronary Arteries and Coronary Slow Flow Phenomenon.

Background: The coronary slow flow phenomenon (CSFP) is an angiographic finding characterised by the delayed passage of contrast through the coronary arteries, despite the absence of obstructive coronary artery disease (defined as less than 50% narrowing of the vessel lumen). Patients with the CSFP experience recurrent angina, for which there are limited evidence-based therapies. Ticagrelor may serve as an effective anti-anginal therapy for these patients by increasing adenosine levels, which could alleviate coronary microvascular dysfunction and its associated angina due to its vasodilatory properties. This study aimed to determine the anti-anginal efficacy of ticagrelor 90 mg taken twice daily on spontaneous angina episodes in patients with refractory angina (i.e., episodes ≥3/week despite two anti-anginals) and documented CSFP. Methods: In a randomised, double-blind, placebo-controlled, cross-over trial, the anti-anginal efficacy of a 4-week ticagrelor therapy regimen was evaluated in 20 patients with refractory angina (mean age 61.5 ± 10.5 years; 40% women) who had documented slow coronary flow. The primary endpoint was the frequency of angina episodes, recorded using an angina diary. Secondary endpoints included the duration and severity of angina episodes, consumption of short-acting nitrates, and health status evaluations using the Seattle Angina Questionnaire (SAQ) and the Short Form-36 (SF-36) indices. Results: During the four weeks of therapy, ticagrelor did not significantly improve angina symptoms compared to the placebo (placebo 25.7 (16.7)) vs. ticagrelor 19.8 (18.1), p > 0.05). Furthermore, it did not impact other patient-related outcome measures, including angina severity, duration, frequency of prolonged angina episodes, nitrate consumption, or the SAQ/SF-36 health outcome indices. No serious adverse events related to the study drug were observed. Conclusions: In patients with documented CSFP who were unresponsive to standard anti-anginal therapy, ticagrelor did not reduce the frequency of spontaneous angina episodes or the consumption of nitrates. Further confirmation of the potential benefits of this therapy may be obtained through a larger clinical trial.

Характеристика пацієнтів з ішемічною хворобою серця та стабільною стенокардією в Україні, оцінка підходів до їх лікування за даними багатоцентрового дослідження GO-OD

Treatment of coronary artery disease (CAD) and stable angina, includes lifestyle modification, pharmacological therapy and invasive interventions to achieve stabilization or regression of the disease. Knowledge of the current situation regarding the use of pharmacological therapy and evaluation of its effectiveness is necessary for further management optimization. Trimetazidine (TMZ) has previously been shown to reduce angina symptoms and increase exercise tolerance in patients with CAD and stable angina and may be among an option for optimizing antianginal treatment. However, the effectiveness of long-term treatment depends on patient adherence, so the use of TMZ once daily (OD) at a dose of 80 mg may improve satisfaction and adherence in patients with CAD and stable angina.Methods. The GO-OD study is a 3-month, non-interventional, observational, multicenter prospective study conducted in Ukraine in a real-world outpatient cardiology practice during February – August 2021. Physicians were instructed to continue monitoring and treating patients in accordance with usual practice and international guidelines. No additional diagnostic or monitoring procedures were performed. Clinical, instrumental and laboratory data, frequency of angina attacks, consumption of short-acting nitrates (SAN), adherence to antianginal drugs, as well as the overall efficacy, tolerability of TMZ OD 80 mg in real-world clinical practice were analyzed. The observation includes regular assessment of patients` clinical status, treatment optimization and its effectiveness at follow up visits.Results. The study included 1529 patients (mean age 62.5 years, 56 % men). In the absence of adequate control of risk factors, pharmacological control of symptoms, and limited use of interventional and surgical treatments, the frequency of angina episodes was high, most patients had a pronounced angina functional class according to the Canadian Society of Cardiology classification (10.5 % – CCS I, 60.1 % – CCS II, 29.5 % – CCS III). Thus, the average number of angina attacks per week in CCS I was 3.7, in CCS II – 5.2, and in CCS III – 7, 97 attacks. In addition to the severity of symptoms, the following pattern was observed: the higher the angina class, the more risk factors and comorbidities patients had. After 3 months of follow-up due to optimization of therapy, there was a significant (p<0.001) decrease in the frequency of angina attacks – from (5.8±4.7 to 1.6±2.0)/week, and the use of SAN – from (4.2±4.3 to 0.8±1.6)/week). At the same time, in 3 month the % of patients with CCS II and III significantly decreased, while the % of patients with CCS I increased (48.4 % – CCS I, 45.7 % – CCS II, 6 % – CCS III). Adherence to medication was improved: 49 % of patients reported high adherence (vs. 18 % at baseline) and 12 % – low adherence (vs. 52 % at baseline). After 3 months of follow-up most of doctors rated the overall tolerability and effectiveness of the therapy as «very satisfied». Patients’ satisfaction with TMZ OD 80 mg therapy after 3 months of follow-up was 9.5 points [on a scale of 1 to 10 (very satisfied)]. Patients’ assessment of daily physical activity increased significantly: 2.42 versus 5.89 points at baseline (on a scale of 1 to 10 (severe limitation)).Conclusions. In general, the management of outpatients with CAD and stable angina in the current cardiologists’ practice, which was complicated by the COVID-19 pandemic, was not effective enough, resulting in a high frequency of angina attacks – almost 6 per week, and a significant limitation of daily activity due to angina symptoms.Significant deficiency in the management of studied population was insufficient correction of such important risk factors as hypertension, heart rate, dyslipidemia, and lifestyle-related risk factors (overweight and obesity, low level of physical activity). The baseline therapy of patients in the study was in line with current guidelines, but with an insufficient frequency of statin prescription (78 %) and ACE inhibitors (54.5 %); antianginal treatment with an average of 2 or more antianginal drugs was not optimal for controlling angina symptoms, and the frequency of coronary revascularization procedures was also insufficient, mostly during acute MI (58.0 %).Optimization of drug therapy as the first step in correcting the condition of patients with CAD and stable angina in accordance with all current recommendations with the inclusion of the original trimetazidine OD 80 mg once daily among antianginal drugs, as well as active monitoring of patients for 3 months allowed to reduce the frequency of angina attacks regardless of its initial FC, increase patient adherence to treatment and their functional activity.

Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

Single-Center Experience With High-Density Spinal Cord Stimulation in Patients With Refractory Angina Pectoris

ObjectivesSpinal cord stimulation (SCS) is a treatment option for patients with refractory angina pectoris (RAP) which was first used in 1987 and led to a reduction in the number of angina pectoris episodes, less consumption of short-acting nitrates, and an improvement in the quality of life. The conventional mode of stimulation leads to paresthesia felt at the target area. In recent years novel modes of stimulation have been developed that are paresthesia free, such as “burst,” “high-density (HD),” or “high-frequency/10 kHz” stimulation. To date, these new modes of stimulation have not been used in patients with RAP and a spinal cord stimulator. This retrospective, single-center, observational study gives a description of the experience of using HD stimulation in selected patients with RAP being treated with SCS. Materials and MethodsAll patients with RAP who received a spinal cord stimulator as treatment at our center from September 2009 to February 2021 were screened. Patients were eligible for inclusion into this retrospective, observational study if 1) patients had used HD stimulation, or 2) were currently using HD stimulation. ResultsFifty-three patients out of a total of 157 patients who had a spinal cord stimulator due to RAP use or have used HD stimulation. In most patients (79.2%), the reason for switching from conventional to HD stimulation was due to progression of symptoms under conventional stimulation. The average duration of conventional stimulation use prior to switching to HD stimulation was 40.3 (± 29.6) months. In total, 26 patients (of 53 patients; 49.1%) were using HD stimulation at the end of the follow-up period or until lost to follow-up, and two patients used both forms of stimulation interchangeably. Five patients (9.4%) had stopped using SCS, and 20 patients (37.7%) switched back to conventional stimulation due to a variety of reasons. ConclusionsThis retrospective study shows that the use of HD stimulation in patients with RAP being treated with SCS could be an alternative option for conventional stimulation. Due to the nature of this study, additional research is essential to confirm these initial findings.

Real-world data from the use of ranolazine in patients with stable angina pectoris: the RANGER study

Abstract Background Although ranolazine is available since years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on effectiveness, tolerability and safety of ranolazine are limited. Methods A non-interventional, prospective study conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. Primary endpoints comprised the weekly frequency of angina attacks, total adverse events and ranolazine discontinuation rate. Secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results In total, 1,101 patients were enrolled in 214 sites. Mean weekly angina attacks were reduced from 3.6±2.9 to 0.4±0.9 (p&amp;lt;0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7±2.2 (p&amp;lt;0.0001). CCS class and QoL were also improved (p&amp;lt;0.0001). Adverse events were reported by 11 (1%) patients totally, while 2 of them (0.2%) were characterized as serious. Treatment was discontinued for any reason in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusion Ranolazine was well-tolerated and effectively reduced angina attacks with simultaneous improvement of CCS class and QoL score in patients with stable angina. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study was sponsored by Menarini Hellas. The study sponsor was involved in the study concept and design and in the interpretation of the data included in this publication, but not in the data collection and analysis. Menarini Hellas also funded the medical writing support for this publication.

Efficacy and Safety of Ivabradine in Combination with Beta-Blockers in Patients with Stable Angina Pectoris: A Systematic Review and Meta-analysis.

IntroductionBeta-blockers are recommended by the European Society of Cardiology as first-line antianginal therapy for reducing heart rate (HR) and symptoms in patients with chronic coronary syndrome, despite a lack of data showing superiority to other antianginal agents. Most patients with angina pectoris require combination therapy to manage symptoms, with a second-line agent chosen to manage the predominant cardiovascular problem. Ivabradine, a selective sinus node If channel inhibitor shown to reduce HR and protect against anginal symptoms, has previously demonstrated noninferior anti-ischaemic and antianginal efficacy to beta-blockers.MethodsThis systematic review and meta-analysis assessed the efficacy and safety of ivabradine in patients with stable angina pectoris who remained symptomatic despite receiving beta-blockers. Keyword searches of PubMed, The Cochrane Central Library Register, ClinicalTrials.gov, The World Health Organization International Clinical Trials Registry Platform (ICTRP) and Google Scholar identified studies comparing ivabradine plus beta-blockers with placebo or other first- or second-line antianginal agents in patients with stable angina pectoris. No date limits or language restrictions were applied. Outcomes were evaluated after 1 and 4 months of treatment, including changes in HR, angina attacks, use of short-acting nitrates, quality of life and safety. Risk of bias was evaluated on the basis of recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.ResultsSeven relevant studies were identified (N = 6821). Ivabradine plus a beta-blocker consistently reduced HR, anginal symptoms and short-acting nitrate consumption within 1 month of initiating therapy, with continued reductions for up to 4 months. Furthermore, ivabradine plus beta-blocker therapy was well tolerated, with bradycardia rarely reported (0.1% of patients overall). This study is limited by the inclusion of only two randomised studies, which may lead to result interpretation bias.ConclusionsIvabradine may be valuable for tailoring early antianginal treatment when used in combination with beta-blockers for chronic stable angina inadequately controlled by beta-blockers.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02222-1.

Effectiveness and Tolerability of Trimetazidine 80Mg Once Daily in Patients with Stable Angina Uncontrolled with Bisoprolol-Based Therapy: The Modus Vivendi Observational Study.

IntroductionModus Vivendi was conducted in routine clinical practice to evaluate the effect of adding trimetazidine 80 mg once daily (TMZ 80 OD) to treat patients with persistent symptoms despite treatment with background antianginal therapies including maximally tolerated bisoprolol.MethodsThis multicenter, prospective, observational, open-label, uncontrolled study recruited adult outpatients with a confirmed diagnosis of stable angina to whom physicians had decided to prescribe TMZ 80 OD. All patients were symptomatic despite treatment, including maximally tolerated doses of bisoprolol. Data on number of angina attacks, use of short-acting nitrates, and quality of life (QoL) were collected at baseline (V1) and at 1-month (V2) and 3-month (V2) follow-up visits. Two sub-analyses assessed efficacy in patients who remained on a stable bisoprolol dose throughout the study, and in patients in whom background antianginal therapy was known.ResultsA total of 1939 patients were recruited (57.2% women). The mean age was 65.6 ± 8.8 years; 73.8% had class II and 26.2% class III angina. At V1, the mean number of angina attacks per week was 6.2 ± 6.5 despite antianginal therapy including maximally tolerated bisoprolol dosage. Following the addition of TMZ 80 OD, this decreased to 3.4 ± 4.2 attacks per week at V2, and 1.6 ± 2.6 at V3 (P < 0.05 at V2 and V3), with concomitant reductions in short-acting nitrate use (P < 0.05). Significant improvements in QoL were observed throughout the study. Subgroup analyses showed that the addition of TMZ 80 OD to guideline-recommended antianginal therapy was associated with significant reductions in the mean number of weekly angina attacks and consumption of short-acting nitrates and improvements in QoL whether patients were treated with maximally tolerated bisoprolol and TMZ 80 OD alone, or maximally tolerated bisoprolol and TMZ 80 OD on top of other antianginal therapies. Treatment was well tolerated.ConclusionThe study findings support the addition of TMZ 80 OD to bisoprolol with or without other antianginal therapies for patients with persistent angina.Trial RegistrationThis study was retrospectively registered under the number ISRCTN29992579.

EFFICACY OF TRIMETAZIDINE IN PATIENTS WITH ACUTE CORONARY SYNDROMES AND CO-MORBIDITIES

Acute coronary syndrome (ACS) is a serious clinical manifestation of coronary artery disease and is the major cause of morbidity and mortality worldwide. Established, that ACS and sudden death cause most IHD-related deaths, which represent 1.8 million deaths per year, with similar numbers of men and women dying from CAD. It is estimated that nearly half of patients with acute coronary syndrome (ACS) have one or more comorbid conditions, which have been linked to poor prognosis. The complexity of clinical decision-making in the presence of multiple comorbidities and the lack of explicit guidelines has been linked to poorer adherence to treatment protocols and worse outcomes for ACS patients. Under-usage of medication and standard-of-care procedures due to the unknown effects of certain therapies for patients with multiple comorbidities (e.g. percutaneous coronary interventions, dual antiplatelet therapy) and worse in-hospital and one year outcomes as well as increased mortality rates have been reported in ACS patients with multiple co-morbidites.&#x0D; Trimetazidine is a second-line medication for treatment stable angina and microvascular angina in European and national guidelines. The efficacy and safety of trimetazidine in ACS patients are under investigation.&#x0D; The purpose of research: to assess the short-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients with ACS and co-morbidities: arterial hypertension and/or 2 type diabetes mellitus.&#x0D; Material and Methods. We observed of 184 patients with ACS with arterial hypertension (AH) and / or 2 type diabetes (DM). The diagnosis was verified by laboratory and instrumental methods according to European Society of Cardiology guidelines (2017, 2020) [10, 11]. All patients were divided into four groups: 1st group - 42 patients with ACS without AH or DM; 2nd group – 56 patients with ACS and previous AH; 3rd group – 42 patients with ACS and 2 type DM; and 4th group – 44 patients with ACS and AH and DM. Due to the treatment strategy patients from each group were divided into 2 subgroups: a – with guidelines-recommended therapy (GRT) and b – with GRT and trimetazidine (TMZ) 35 mg twice a day. The following laboratory tests were performed, in our trial: blood glucose, HbA1c, serum urea, serum creatinine, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, serum sodium, serum potassium, CRP, cardiac troponin I, NT-proBNP.&#x0D; Results. The mean age of all observed patients with ACS was 64.6±11.9 years; 93 (50.5%) were males and 91 (49.5%) females among them (see table 1). ACS without persistent ST segment elevation was diagnosed in 44 (23.9%) cases; instead ACS with persistent ST segment elevation – in 140 (76.1%) cases. In all trimetazidine treatment groups, the weekly frequency of angina symptoms showed the significant reductions at 28-day visit compared with baseline (p&lt;0.05). Similar, the short-acting nitrate consumption was significant low during the course of treatment with trimetazidine (p&lt;0.05). Additional prescription of trimetazidine had significant effects for decrease of glucose, LDL cholesterol, CRP and NT-proBNP levels in patients with ACS and co-morbidities. Any serious adverse events were detected in the trimetazidine groups or in the placebo groups.&#x0D; Conclusions. Additional prescription of trimetazidine has significant effects for decrease of glucose, LDL cholesterol, CRP and NT-proBNP levels in patients with ACS and arterial hypertension and/or 2 type diabetes mellitus and has good safety.

Effectiveness of Trimetazidine in Patients with Stable Angina Pectoris of Various Durations: Results from ODA.

IntroductionTrimetazidine (TMZ) is an antianginal agent that acts directly at the myocardial cell level and which is now available in a once-daily (od) formulation.MethodsODA, a 3-month, observational, multicenter study in Russia, assessed the effectiveness and tolerability of TMZ 80 mg od in patients with stable angina and persisting symptoms, in real-life settings. The present analysis explored the effects of adding TMZ to background antianginal treatment with respect to the duration of stable angina.ResultsA total of 3032 patients were divided into four groups according to stable angina pectoris duration since diagnosis, ranging from less than 1 year to more than 10 years. A decrease in frequency of angina attacks was observed, including in patients with angina duration < 1 year, in whom the frequency of weekly angina attacks decreased from 3.8 ± 2.9 to 1.4 ± 1.7 at 1 month and 0.6 ± 1.0 at 3 months. Short-acting nitrate consumption and proportion of angina-free patients decreased, and self-reported physical activity and adherence to antianginal therapy improved in all patient groups, including recently diagnosed patients and starting already at month 1.ConclusionsAddition of TMZ 80 mg od to antianginal treatment was effective in reducing the frequency of angina attacks and the use of short-acting nitrates, improving Canadian Cardiovascular Society (CCS) class, self-reported physical activity, and adherence to antianginal therapy. These beneficial effects were observed in patient groups with different durations of stable angina, suggesting an opportunity for decreasing angina burden even in recently diagnosed patients.Trial RegistrationISRCTN registry Identifier, ISRCTN97780949.Electronic supplementary materialThe online version of this article (10.1007/s40119-020-00174-7) contains supplementary material, which is available to authorized users.

Efficacy and safety of oral Guanxinshutong capsules in patients with stable angina pectoris in China: a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial

BackgroundTo assess the efficacy and safety of oral Guanxinshutong (GXST) capsules in Chinese patients with stable angina pectoris (SAP) in a prospective, multicenter, double-Blind, placebo-controlled, randomized clinical trial (clinicaltrials.gov Identifier: NCT02280850).MethodsEligible patients were randomized 1:1 to the GXST or placebo group. Current standard antianginal treatment except for nitrate drugs was continued in both groups, who received an additional 4-week treatment of GXST capsule or placebo. Primary endpoint was the change from baseline in angina attack frequency after the 4-week treatment. Secondary endpoints included the reduction of nitroglycerin dose, score of Seatntle Agina Questionnaire, exercise tolerance test defined as time to onset of chest pain and ST-segment depression at least 1 mm greater than the resting one.ResultsA total of 300 SAP patients from 12 centers in China were enrolled between January 2013 and October 2015, and they were randomly divided into the GXST group and the placebo group (150 patients in each group). Of whom, 287 patients completed the study (143 patients in the GXST group, 144 patients in the placebo group). The baseline characteristics of the two groups were comparable. After 4-week treatment with GXST capsules, the number of angina attacks and the consumption of short-acting nitrates were significantly reduced. In addition, the quality of life of patients were also substantially improved in the GXST group. No significant differences in the time of onset of angina and 1-mm ST segment depression were noted between the two groups. 7 patients (4.1%) in the GXST group and 3 patients (2.1%) in the placebo group reported at least one adverse event, respectively.ConclusionsGXST capsules are beneficial for the treatment of SAP patients.

Effectiveness and Impact on Adherence of a New Fixed-Dose Combination of Ivabradine and Metoprolol in a Wide Range of Stable Angina Patients in Real-Life Practice.

IntroductionThe antianginal effectiveness of ivabradine administration in addition to beta-blockers has been shown in patients with stable angina. The first fixed-dose combination (FDC) of ivabradine and metoprolol is now available and its evaluation in various stable angina patient populations relevant to clinical practice would be useful.MethodsIn this 4-month, prospective, multicenter, observational study, the effectiveness and tolerability of the metoprolol/ivabradine FDC was assessed in patient subgroups specified according to age, coronary artery disease (CAD) duration, Canadian Cardiovascular Society (CCS) class, co-morbidities, and previous myocardial infarction (MI) or revascularization. Heart rate (HR), angina attack frequency, short-acting nitrate (SAN) consumption, functional status, and medication adherence were documented at baseline and after 4 months of follow-up.ResultsA total of 747 stable angina patients were included and divided into subgroups. At 4 months, a significant decrease in HR, angina attack frequency, and SAN consumption per week was consistently observed across all patient subgroups. The proportion of CCS class I patients increased significantly from baseline to month 4. In all patient subgroups, at 4 months, a significant increase was observed in the proportion of patients with self-reported complete adherence. Complete adherence at the final visit was found to decrease with an increasing number of medications. Physicians evaluated the effectiveness and tolerability of the FDC as ‘very good’ and ‘good’ for more than 96% of patients in all analyzed patient subgroups.ConclusionsTreatment with metoprolol/ivabradine FDC significantly improved angina symptoms and adherence, with an excellent tolerability profile, in stable angina patient subgroups relevant to real-life clinical practice, regardless of age, CAD duration, CCS class, comorbidities, previous MI, or history of revascularization.Trial registrationISRCTN51906157.FundingThis study was sponsored by Servier Deutschland GmbH. Editorial assistance and the Rapid Service Fee were funded by Servier, France.Plain Language SummaryPlain language summary available for this article.

Effectiveness of Long-acting Trimetazidine in Different Clinical Situations in Patients with Stable Angina Pectoris: Findings from ODA Trial.

IntroductionTrimetazidine (TMZ) has been shown to be efficacious for angina treatment. The TMZ 80-mg formulation allows one-daily (od) dosage, which could improve symptom control and adherence.MethodsThe 3-month, observational, multicenter, prospective ODA (antianginal effectiveness and tolerability of trimetazidine modified release 80 mg Once Daily in stable Angina patients in real-world practice) study assessed TMZ 80 mg od effectiveness in stable angina patients with persistent symptoms despite therapy. Two clinical situations were compared: patients who initiated treatment with TMZ 80 mg od (initiation group) and patients who were previously treated with TMZ 20 mg thrice daily (tid) or TMZ 35 mg MR twice daily (bid) and switched to TMZ 80 mg od (switch group). Number of angina attacks, short-acting nitrate (SAN) consumption, self-reported patient daily activity, Canadian Cardiovascular Society (CCS) class, adherence to antianginal therapy, overall efficacy and tolerability were assessed.ResultsA significant decrease in weekly number of angina attacks was observed for both the initiation group (n = 1841 patients) from 4.8 ± 3.5 at baseline to 0.9 ± 1.4 at 3 months (M3) (P < 0.001), and the switch group (n = 1216 patients) from 4.4 ± 1.3 at baseline to 0.9 ± 1.3 at M3 (P < 0.001). Significant reduction in SAN consumption and improvement in CCS class were observed for both groups. Adherence to antianginal therapy improved in both groups at 1 month (M1) and M3. Overall effectiveness of TMZ 80 mg od was rated by physicians as “very good” (68% initiation group, 70% switch group), “good” (31% initiation group, 29% switch group), “moderate” (1%, both groups) or “poor” (< 1%, both groups). Overall tolerability of TMZ 80 mg od was rated by physicians as “very good” (75%), “good” (25%) or “moderate” (< 1%) in both groups.ConclusionsTMZ 80 mg od, in association with other antianginal therapy, effectively reduced angina attacks and SAN consumption and improved physical activity and adherence to antianginal therapy both in patients initiating TMZ treatment and those switching from a bid or tid formulation.Trial RegistrationISRCTN registry Identifier, ISRCTN97780949.FundingServier.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s40119-019-0128-3) contains supplementary material, which is available to authorized users.

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80Mg Once Daily in Stable Angina Patients in Real-World Practice.

IntroductionTrimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.MethodsODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.ResultsA total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p < 0.001) decrease in angina attack frequency (from 4.7 ± 3.5 to 0.9 ± 1.3/week) and SAN use (from 4.5 ± 3.9 to 0.7 ± 1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p < 0.0001) and non-adherence by 3% (vs. 36% at baseline, p < 0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p < 0.01), slight limitation (46% vs. 5% at baseline, p < 0.001) or moderate limitation (30% vs. 23%, p < 0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p < 0.001) or very marked reduction (1% vs. 19% at baseline, p < 0.01) at month 3.ConclusionIn this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.Trial RegistrationISRCTN registry Identifier, ISRCTN97780949.FundingServier.Plain Language SummaryPlain language summary available for this article.

Treatment of Stable Angina with a New Fixed-Dose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice.

IntroductionIn this prospective, multicenter, observational cohort study, the effectiveness and tolerability of the first fixed-dose combination (FDC) formulation of the selective heart rate reducing agent ivabradine and the beta-blocker metoprolol was evaluated in stable angina pectoris (AP) patients in a clinical practice setting.MethodsStable AP outpatients received a FDC of ivabradine and metoprolol (b.i.d.) for 4 months, in addition to cardiovascular standard therapy. Resting heart rate (HR), number of angina attacks, short-acting nitrate consumption, severity of symptoms (assessed by patient judgment and documented by CCS score) and tolerability were documented. Medication adherence was assessed by a modified four-item Morisky questionnaire. Descriptive statistics were performed on all data.ResultsA total of 747 stable AP patients (mean age, 66.4 years, 62% male, 50% and 31% with previous PCI and myocardial infarction, respectively) were included. Apart from ivabradine and beta-blockers as free combination, most frequently used concomitant standard medications at baseline were aspirin (68%), statins (71%), ACEI/AT1-blockers (76%), diuretics (35%), and calcium antagonists (15%). Highly prevalent comorbidities were hypertension (86%), hyperlipidemia (65%), and diabetes (35%). After 4 months, switch to treatment with the FDC was associated with a significant reduction in mean HR by 10 bpm. Proportion of patients with ≥ 1 angina attacks/week decreased from 38 to 7%. Patients in CCS class 1 increased (25 to 63%), while they decreased in CCS class 3 (19 to 5%). Medication adherence was also significantly improved (p < 0.001 for all changes from baseline). Mostly mild adverse events were documented in 5.4% of patients.ConclusionsIn these stable AP patients in a real-life setting, treatment with a FDC of ivabradine and metoprolol was associated with reduced HR and angina symptoms, while exercise capacity (CCS score) was improved. These effects may be mainly mediated by the increased medication adherence of patients observed with use of the FDC formulation.FundingServierTrial registration numberISRCTN51906157

Effectiveness of Ivabradine Treatment in Different Subpopulations with Stable Angina in Clinical Practice: A Pooled Analysis of Observational Studies

Objectives: The efficacy of ivabradine has been demonstrated in different subpopulations of stable angina patients in randomized clinical trials. This study explored its effectiveness in subpopulations seen in clinical practice as they often differ from those of randomized trials. Methods: Data were pooled from three German observational studies with similar inclusion criteria (stable angina and heart rate ≥60 bpm). All patients received 2.5, 5, or 7.5 mg b.i.d. of ivabradine for 4 months, with or without concomitant beta-blocker. Antianginal effectiveness was analyzed in subpopulations defined by gender, age, heart rate, angina severity, use of concomitant beta-blocker, previous percutaneous coronary intervention procedure, and comorbidities (including previous myocardial infarction and diabetes). Results: Treatment data were available on 8,555 patients, where therapy with ivabradine was associated with a significant reduction in the frequency of angina attacks and consumption of short-acting nitrates of 87%. Effectiveness was maintained in all investigated subpopulations, with a reduction in antianginal parameters of 82-90%. Clinical status (Canadian Cardiovascular Society class) and quality of life were also improved. Ivabradine was well tolerated in all subgroups. Conclusions: Ivabradine is effective and safe in all subpopulations of angina patients seen in clinical practice, independent of age, comorbidities, and use of beta-blocker.

Ivabradine in Combination with Metoprolol Improves Symptoms and Quality of Life in Patients with Stable Angina Pectoris: A post hoc Analysis from the ADDITIONS Trial

Objectives: Elevated heart rate can increase myocardial oxygen demand and reduce myocardial perfusion, provoking myocardial ischemia and angina symptoms. We evaluated adding ivabradine to the therapy of patients on metoprolol. Methods: ADDITIONS (prActical Daily efficacy anD safety of Procoralan® In combinaTION with betablockerS) was a multicenter, 4-month, noninterventional, prospective, open-label trial that involved stable-angina patients. Along with metoprolol, patients received ivabradine (5 or 7.5 mg, b.i.d.). We investigated the effect of ivabradine on heart rate, angina attacks, nitrate consumption, quality of life (QoL) and tolerability as well as the influence of baseline heart rate. Results: Heart rate fell by 19.7 ± 11.2 bpm, with an 8-fold decrease in weekly angina attacks (1.7 ± 2.2 to 0.2 ± 0.7) and nitrate consumption (2.4 ± 3.4 to 0.3 ± 0.9). Patient numbers in Canadian Cardiovascular Society class I more than doubled (i.e. from 29 to 65%) and QoL improved (the EQ-5D index and visual analog scale scores rose from 0.68 ± 0.27 to 0.84 ± 0.20 and 58.1 ± 18.4 to 72.2 ± 15.5 mm, respectively). The effect of ivabradine was greater in patients with a baseline heart rate ≥70 bpm (mean reduction in heart rate -21.2 ± 10.4 bpm, with a relative reduction in angina attacks and short-acting nitrate consumption of 87.1 and 87.2%, respectively). Conclusions: Ivabradine combined with metoprolol safely and effectively reduces heart rate, angina attacks and nitrate use, and improves QoL in stable-angina patients.

Ivabradine in combination with beta-blocker reduces symptoms and improves quality of life in elderly patients with stable angina pectoris: Age-related results from the ADDITIONS study

BackgroundClinical trials have proven the anti-anginal and anti-ischemic efficacy of the pacemaker current inhibitor ivabradine in combination with beta-blockers in patients with stable angina pectoris (AP). This retrospective subgroup analysis of the ADDITIONS study evaluated the effectiveness and tolerability of ivabradine combined with beta-blockers, and its effects on angina symptoms and quality of life in elderly patients ≥75years in everyday practice. MethodsIn the non-interventional, multicenter, prospective, open-label ADDITIONS study 2330 patients with stable AP of different age groups were treated with a flexible dose of ivabradine twice daily in addition to beta-blockers for 4months. Heart rate (HR), number of angina attacks, nitrate consumption, tolerance, and quality of life (QoL) were evaluated. A subgroup analysis was performed, focusing on 479 patients (21%) ≥75years. ResultsIn these 479 patients ≥75years ivabradine (mean dose 11.61±3.18mg per day) after 4months of treatment reduced HR by 19.2±11.6bpm to 65.4±8.3bpm. The average number of angina attacks per week was decreased by 1.6±1.8 to 0.4±1.3 and the average consumption of short-acting nitrates per week was reduced by 2.2±3.2 to 0.6±1.8units (both p<0.0001). There was a marked shift in Canadian Cardiovascular Society (CCS) grade distribution with most patients (57%) now classified as CCS grade I, and 42% as CCS grades II and III. This was accompanied by an improvement in EQ-5D QoL index to 0.75±0.22 (p<0.0001). Tolerability of ivabradine treatment was rated by the physicians as “very good/good” for 72%/28% of elderly patients. ConclusionsIn daily clinical practice, addition of ivabradine to beta-blockers was effective in reducing HR, angina attacks and nitrate consumption in elderly patients (≥75years) with stable angina pectoris. In addition, a marked improvement of CCS symptom scores and QoL was demonstrated. Treatment was generally well tolerated.

Long-term therapy with ivabradine in combination with beta-blockers in patients with stable angina pectoris and effect of beta-blocker background dose: results from the ADDITIONS 1-year follow-up

Objectives: The non-interventional multicenter ADDITIONS study follow-up evaluated the effectiveness, safety, and effect on quality of life (QoL) of ivabradine (iva) in combination with betablockers over one year. Methods: Resting heart rate (HR), the number of angina attacks, nitrate consumption, and concomitant medications were documented in 901 patients with chronic stable angina treated with iva twice daily in flexible doses in combination with betablockers for one year. QoL was evaluated by the EQ-5D patient questionnaire at each visit. A descriptive statistical analysis was performed. Results: 901 patients (intention to treat, mean age 65.4±10.6 years, 58% male) with chronic stable angina were analyzed. 53% of the patients had undergone a PCI or CABG before and 35% had a history of myocardial infarction. All patients received betablockers (e.g. Metoprolol 41%, mean daily dose (mdd) 109.6 mg; Bisoprolol 39%, mdd 6.9 mg; Nebivolol 13%, mdd 4.9 mg; Carvedilol 7%, mdd 28.9 mg) and concomitant standard medication. At baseline, most patients (49%) were classified CCS grade II, mean HR was 86.1±12.6 bpm, a mean of 1.7±2.2 angina attacks per week were reported, consumption of short-acting nitrates was 2.3±3.2 units per week, and the EQ-5D index was 0.66±0.28. After one year, iva (mean dose 12.53±2.84 mg per day) had reduced HR by 20.7±14.0 bpm to 65.4±8.8 bpm, the number of angina attacks by 1.4±2.5 per week (p<0.0001, Wilcoxon signed rank test), and nitrate consumption by 1.9±3.1 units per week (p<0.0001), had improved EQ-5D index by 0.18±0.27 (p<0.0001), and most patients (63%) were classified CCS grade I. HR reduction and improvement of angina symptoms by iva was similar in three subgroups defined by betablocker background dose (<50%, 50% to 99%, and ≥100% of recommended target dose): see table. View this table: Table 1 Conclusion: Over one year the combination of iva with betablockers in clinical practice not only effectively reduced HR, number of angina attacks, and nitrate consumption, but also improved QoL and CCS class in patients with stable angina. Moreover, the treatment effect of iva on HR and angina symptoms was independent of background betablocker dose.

Effectiveness of the original trimetazidine MR in patients with stable coronary heart disease and angina attacks resistant to trimetazidine generics (ETALON study)

Aim. To assess the clinical benefits of the original trimetazidine medication (Preductal® MR) in patients with stable coronary heart disease and angina attacks resistant to trimetazidine generics. Material and methods. The study included 112 patients with stable coronary heart disease (CHD), who experienced angina attacks, despite the treatment with trimetazidine generics added to the standard CHD therapy (antiaggregants, statins, β-аadrenoblockers, ACE inhibitors). All participants received Preductal® MR (35 mg twice a day) instead of trimetazidine generics. The follow-up duration was 3 months. Treatment effectiveness was assessed by the changes in angina attack incidence, short-acting nitrate consumption, and general status, using a visual analogue scale (VAS). In addition, pharmaco-economic analysis of the treatment effectiveness was performed. Results. The replacement of trimetazidine generics with Preductal® MR was associated with a reduction in angina attack incidence by 63 % and in the number of nitroglycerine tablets/doses by 65 % (p&lt;0,01). VAS score increased from 45,3±13,8 to 71,6±11,9 (р&lt;0,0001). Preductal® MR therapy is the best pharmaco-economic option, since the ratio between weekly treatment costs (RUB) and the weekly number of prevented angina attacks is minimal for this original medication. Conclusion. In patients with stable CHD and angina attacks, resistant to trimetazidine generics, Preductal® МR therapy is associated with a significant reduction in angina attack incidence and consumption of short-acting nitrates. Preductal® MR is the most cost-effective medication, providing optimal effectiveness with minimal costs.

Long-term effects of spinal cord stimulation on angina symptoms and quality of life in patients with refractory angina pectoris—results from the European Angina Registry Link Study (EARL)

ObjectiveTo assess the long-term effect of spinal cord stimulation (SCS) on angina symptoms and quality of life in patients with refractory angina pectoris defined as severe angina due to coronary...