ramipril and Cough

To compare the efficacy and safety of once-daily telmisartan and ramipril on blood pressure (BP) reductions during the last 6 h of the dosing interval.. In a prospective, randomized, open-label, blinded-endpoint study using ambulatory BP monitoring, 801 patients with mild-to-moderate hypertension were randomly assigned to once-daily treatment with telmisartan 80 mg for 14 weeks or ramipril 5 mg for 8 weeks and then force titrated to ramipril 10 mg for the last 6 weeks. Primary endpoints were the reduction from baseline in the last 6-h mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Secondary endpoints included changes in 24-h, morning, daytime and night-time mean ambulatory BP and ambulatory BP response rates.. Telmisartan 80 mg produced greater reductions in the last 6-h mean ambulatory SBP and DBP compared with ramipril 5 mg (P < 0.0001) and 10 mg (P < 0.0001), and was superior to ramipril for all secondary ambulatory SBP and DBP endpoints (P < 0.05). Ambulatory BP response rates (24-h mean ambulatory SBP/DBP < 130/80 mmHg or reduction from baseline > or = 10 mmHg) were greater with telmisartan 80 mg (P < 0.01) than with ramipril 5 and 10 mg. Ramipril was associated with a higher incidence of treatment-related cough (5.7 versus 0.5% for telmisartan).. Telmisartan was significantly more effective than ramipril in reducing BP throughout the 24-h dosing interval and particularly during the last 6 h, a time when patients appear to be at greatest risk of cerebro- and cardiovascular events. Both drugs were well tolerated, although ramipril was associated with a higher incidence of cough.

Topics: Adolescent; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cough; Female; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Ramipril; Single-Blind Method; Telmisartan; Time Factors

In this study, the tolerability and safety of ramipril, as monotherapy and in combination with a low dose of furosemide, were assessed in patients with mild-to-moderate hypertension in general practice. After a placebo run-in phase, patients received ramipril as monotherapy in a dose of 2.5 to 5 mg daily for 6 weeks. Nonresponders (diastolic blood pressure greater than 90 mm Hg) entered a double-blind treatment period, and received either 10 mg of ramipril daily, or 5 mg of ramipril in combination with 20 mg of furosemide daily. The tolerability of the study medication was assessed by reported adverse events, and by monitoring blood cell count, electrolytes, serum creatinine, fasting blood glucose, and apolipoproteins AI and B. Of a total of 770 patients who entered the placebo run-in phase, 661 patients were enrolled in the first active treatment period. The most commonly reported adverse events were headache, cough, dizziness, asthenia, cramps, diarrhea, and nausea, but not all of these events were related to ramipril treatment. A total of 38 patients discontinued active treatment due to nonserious adverse events, mainly cough, dizziness, or diarrhea. There appeared to be a relationship between the prevalence of cough and ramipril dosage; however, an increased incidence of cough was also observed during outbreaks of influenza in France. There were no significant changes in laboratory variables during the study.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Cell Count; Bridged Bicyclo Compounds; Cough; Double-Blind Method; Family Practice; Female; Furosemide; Humans; Hypertension; Male; Middle Aged; Ramipril

To find out whether enalapril or ramipril causes the sensitivity of the cough reflex to change or symptomatic cough to develop in patients with hypertension.. Prospective, placebo controlled, double blind, randomised crossover study.. Academic units of clinical pharmacology and medicine.. 20 Patients (nine men and 11 women) who needed to take angiotensin converting enzyme inhibitors to control hypertension.. All patients received enalapril 10 mg daily, ramipril 10 mg daily, or placebo daily for one week in random order, with a washout period of at least one week between treatments. For assessment of sensitivity of the cough reflex the patients inhaled various concentrations of capsaicin solution in random order.. Measurement of the doses of capsaicin required to cause two or more and five or more coughs or the development of a symptomatic cough.. Blood pressure, symptoms of cough, and the sensitivity of the cough reflex to inhaled capsaicin were recorded at the start of the study and before and at the end of each treatment period. Plasma urea and creatinine concentrations and angiotensin converting enzyme activity were measured at the start of the study and the end of each treatment period. Data were analysed by two way analysis of variance. Mean blood pressure was 159/97 mm Hg at the start of the study and 152/92, 143/88, and 147/86 mm Hg after treatment with placebo, enalapril, and ramipril respectively. Mean (SE) plasma angiotensin converting enzyme activity was 2.2 (0.2) mmol/l/h after treatment with placebo and fell significantly to 1.3 (0.1) mmol/l/h and to 0.4 (0.1) mmol/l/h after treatment with enalapril and ramipril respectively. No patient complained of cough while taking placebo but three women complained of cough when taking both enalapril and ramipril. The mean (95% confidence interval) lowest dose of capsaicin causing two or more coughs was 2.4 (1.5 to 4.0), 1.8 (1.12 to 2.82), and 2.2 (1.7 to 3.0) nmol after treatment with placebo, enalapril, and ramipril respectively; none of these changes were significant. The lowest dose of capsaicin causing five or more coughs was 18.9 (13.9 to 25.8), 14.4 (8.4 to 24.5), and 15.3 (10.8 to 21.2) nmol respectively; none of these changes were significant. The three patients who complained of cough had normal sensitivity to capsaicin after treatment with placebo but had a considerably increased sensitivity after treatment with enalapril and ramipril.. Both enalapril and ramipril increase the sensitivity of the cough reflex appreciably in patients who complain of cough during treatment, but they do not change the se

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Clinical Trials as Topic; Cough; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Prospective Studies; Ramipril; Random Allocation; Reflex

The hypertension is a civilization disease, slowly destroying the cardio-vascular system and leading to serious complications, which may result in patient death. Critical factors enhancing the proper functioning of the body are: properly selected pharmacotherapy and the self-control of the blood pressure.. was to evaluate the effectiveness and safety of the hypertension treatment with generic and original formulations of angiotensin converting enzyme (ACE) inhibitors.. To the study, which consisted of an interview and completed a joint survey were enrolled 120 patients with hypertension therapy based on formulations of ACE inhibitors group. Data for the analysis were obtained from surveys conducted in: Department of Angiology, Hypertension and Diabetology, Department and Clinic of Endocrinology, Diabetology and Isotope Therapy and its Clinic for Diabetic Outpatients, in the period from 03/02/2011 to 20/04/2011.. Out of 120 surveyed hypertensive patients treated with ACEI, 79 persons (66%) received the original preparations and 41 (34%) generic medications. Most preparations contained ramipril: 78 patients, of whom 50 received the original formulations and 28 a generic one. In this population no differences were found in the reduction of the systolic and the diastolic blood pressure between groups of patients receiving original and generic formulations. The most common adverse effects (AE) reported by patients were cough (n = 16), hypotension (n = 7), paresthesia (n = 6), skin lesions (n = 6), weakness (n = 5), headache and dizziness (n = 5). Some of these, i.e.: cough, weakness, headaches and dizziness, occurred more frequently in patients receiving therapy with generic preparations.. Both the reference and generic preparations showed similar efficacy in reducing systolic and diastolic pressure. The therapy with original drugs leads less frequently to adverse effects such as cough, weakness, headaches and dizziness.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cough; Dizziness; Drug Eruptions; Drugs, Generic; Female; Headache; Humans; Hypertension; Hypotension; Male; Muscle Weakness; Paresthesia; Population Surveillance; Ramipril

Dry cough is a common cause for the discontinuation of ramipril treatment. The aim of this pharmacoepidemiological study was to assess the incidence of ramipril-related cough among the Polish population and to characterize patients at risk of experiencing the adverse effect of cough during ramipril treatment.. This was a prospective observational study involving 10,380 patients treated with ramipril for a period of no longer than 8 weeks, consisting of 3 visits: baseline, first follow-up (after 4-8 weeks) and second follow-up visit (after 4-8 weeks of cessation of ramipril, conducted only for evaluating coughing patients).. The incidence of ramipril-related cough was 7.1%. Logistic regression analysis identified female sex (OR=1.35), cigarette smoking (OR=2.50), chronic obstructive pulmonary disease (OR=1.70), asthma (OR=1.60) and previous history of tuberculosis (OR=6.20) to be significantly and independently associated with the onset of ramipril-related cough. Coughing subsided within a period of 2-20 days after ramipril was discontinued. In all patients reporting the appearance of cough within the first 5 days after therapy initiation, the adverse effect subsided after therapy discontinuation. If cough appeared within 6-10 days, it subsided after discontinuation in 81.6% of subjects. Cough persisted in 30.4% of those reporting later onset.. 1. Female sex, cigarette smoking, COPD, asthma, and previous history of tuberculosis increase the risk of ramipril-related cough. 2. The later the cough occurs during treatment, the less often the drug is the causative agent and the cough and also less likely to disappear after discontinuation of ramipril.

Topics: Asthma; Cough; Female; Humans; Incidence; Logistic Models; Male; Odds Ratio; Pharmacoepidemiology; Poland; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Ramipril; Risk Factors; Sex Factors; Smoking; Tuberculosis

Dry and persistent cough is one of the commonest side effects experienced by patients treated with angiotensin-converting enzyme (ACE) inhibitors for the therapy of hypertension and congestive heart failure. The present study investigated the effect of zofenopril and ramipril on cough induced by citric acid in guinea pig and the involvement of bradykinin (BK) and prostaglandin E2 (PGE2) in mediating the responses of these drugs. Zofenopril (10 mg/kg) or ramipril (3-10 mg/kg), which is threefold more potent than zofenopril, on a mg basis, in lowering blood pressure, was orally administered daily in drinking water for 2 weeks. At the end of this period, aerosol of citric acid solution (0.1 M) was performed and the number of cough counted for 10 min. The role of the kinin B(2) receptor was also investigated. BK and PGE2 levels in the bronchoalveolar lavage (BAL) fluid were measured after repeated oral treatment with zofenopril or ramipril (10 mg/kg). Ramipril (3-10 mg/kg) increased citric acid-induced cough by 40% and 60%, respectively, as compared to the vehicle control group (15.0 ± 1.8), while zofenopril (10 mg/kg) was without effect. The enhancement of citric acid-induced cough caused by ramipril (10 mg/kg) was reduced by the kinin B(2) receptor antagonist MEN16132 (0.25 mg/kg ip). BK and PGE2 levels in the BAL fluid were increased, in comparison to the control group, after ramipril treatment, while they were unchanged after zofenopril administration. Zofenopril, contrary to ramipril, did not affect either citric acid-induced cough in the guinea pigs or BK and PGE2 production in the airways.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin B2 Receptor Antagonists; Bronchoalveolar Lavage Fluid; Captopril; Citric Acid; Cough; Dinoprostone; Dose-Response Relationship, Drug; Drug Synergism; Guinea Pigs; Male; Ornithine; Ramipril; Sulfonamides

Cough is the most common symptom reported by patients in a primary care setting and is one of the most frequent secondary effects recorded during treatment with angiotensin-converting enzyme (ACE) inhibitors. The aim of the current study was to analyze potential differences in cough induction between 2 structurally different ACE inhibitors, namely zofenopril, which has a sulphydryl moiety, and ramipril, which has a carboxyl moiety. The cough reflex was induced by chemical (citric acid) and/or mechanical stimulation of the tracheobronchial tree in awake and anesthetized rabbits. Intravenous injection of the active compounds of the 2 ACE inhibitors, zofenoprilat (288 nmol/kg) and ramiprilat (129 nmol/kg), caused similar hypotensive effects in anesthetized rabbits. None of the studied cough-related variables changed in response to ACE inhibitor administration, with the exception of the number of coughs. Ramiprilat, but not zofenoprilat, increased the cough response induced by both mechanical and chemical stimulation (1 mol/L citric acid aerosol) of the tracheobronchial tree. In awake animals, zofenoprilat- or vehicle-treated rabbits did not show any significant changes in the number of coughs induced by 1 mol/L citric acid aerosol compared to their respective basal values (from 15.2 ± 2.3 to 13.1 ± 1.3 and from 16.1 ± 4.9 to 15.8 ± 4.3, respectively). Conversely, ramiprilat resulted in a significant increase in the number of coughs (from 21.1 ± 2.6 to 34.9 ± 3.5; P < .01). These findings confirm that there are differences in the cough potentiation effect induced by different ACE inhibitors. The low rate of cough seen with zofenoprilat may be related to its ability to induce a lower accumulation of bradykinin and prostaglandins at the lung level.

Topics: Anesthesia, Intravenous; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Captopril; Citric Acid; Consciousness; Cough; Drug Evaluation, Preclinical; Injections, Intravenous; Male; Rabbits; Ramipril; Reflex

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Coronary Thrombosis; Cough; Cytochrome P-450 CYP2C9; Genotype; Heart Failure; Humans; International Normalized Ratio; Losartan; Male; Middle Aged; Pharmacogenetics; Polypharmacy; Ramipril; Warfarin

Topics: Amides; Cough; Fumarates; Humans; Hypertension; Incidence; Ramipril; Randomized Controlled Trials as Topic

To assess the safety and tolerability of ramipril 10 mg in patients at high risk of cardiovascular (CV) events by observing the levels of blood pressure (BP) and by recording the incidence of cough in these patients, a study was conducted in a total of 1048 patients who participated in the registry. Eligible patients in this prospective, observational, longitudinal, multicentre registry included all normotensives--including treated hypertensives--with BP <140/90 mm Hg, a history of coronary aritery disease and a history of cerebrovascular disease, peripheral arterial disease or diabetes (with micro-albuminuria) or dyslipidaemia, in whom ramipril was indicated for CV risk reduction and had been prescribed by the treating physician. The primary outcome was the effect on BP at 8 weeks, and the secondary outcome was the incidence of cough at 8 weeks. Ramipril was initiated at 2.5 mg once daily (OD) for a week, followed by 5 mg OD for 3 weeks and was then increased to 10 mg OD. Data was analysed using ANOVA and Chi-square test. A total of 1,048 patients participated in this registry; 868 (82.82%) continued with the treatment till the end of the registry (ie, 8 weeks). At baseline, systolic BP was 130.10 +/- 5.38 mm Hg, while diastolic BP was 81.07 +/- 4.36 mm Hg. At 8 weeks, these values changed non-significantly to 123.41 +/- 6.33 mm Hg and 79.03 +/- 4.84 mm Hg, respectively. At week 1, 41 patients had cough, which increased non-significantly to 58 by week 8. Only 6 patients complained of severe cough at week 8, which did not lead to treatment discontinuation. Tolerability of the treatment was assessed to be 'excellent' or 'good' by 63.3% patients and 67% physicians. Treatment with ramipril 10 mg daily in patients with high risk of CV events and normal/ controlled BP produced neither a significant fall in BP nor significant adverse events in real-world clinical practice and was well tolerated.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Cough; Diastole; Drug-Related Side Effects and Adverse Reactions; Humans; Hypertension; Longitudinal Studies; Product Surveillance, Postmarketing; Prospective Studies; Ramipril; Risk Factors; Risk Reduction Behavior; Systole

The HOPE TIPS study assessed the practicality and tolerability of ramipril titration to a target dose of 10 mg (as achieved in definitive efficacy studies) in a clinical practice setting. 3881 patients at high cardiovascular risk (HOPE study criteria) were recruited in primary and specialist care settings in 9 countries by 439 investigators. Dose titration of ramipril from 2.5 mg to 10 mg daily took place over 9-12 weeks. The mean age of the patients was 64 years, 60% were male and 79% Asian. The target dosage of 10 mg daily was reached in 73% of patients with 96% of patients achieving 5 mg or 10 mg daily. During the study period uncontrolled hypertension (> 160/90) was recorded in 15% of patients, myocardial infarction or unstable angina 1.6%, heart failure 0.4%, new diabetes 0.6%. Only 9.8% of patients discontinued treatment with 5.9% attributed to treatment side-effects and 4% related to cough. The large majority of patients in a wide range of clinical practice settings with high cardiovascular risk can be treated with ramipril titrated to 10 mg daily with good tolerability.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Cough; Female; Humans; Male; Middle Aged; Prospective Studies; Ramipril

The Heart Outcomes Prevention Evaluation (HOPE) study demonstrated that the angiotensin-converting enzyme inhibitor, ramipril, significantly reduces mortality, myocardial infarction and stroke in high-risk cardiovascular patients, beyond the benefits from blood pressure lowering. The tolerability of ramipril 10 mg/day has been an important concern when applying these results. Following the same criteria as the HOPE study, we investigated the adverse effects profile and tolerability of 10 mg ramipril in high-risk patients at our institution. In total, 92 patients with high cardiovascular risk were eligible for this study. Initially, ramipril was prescribed 2.5 mg orally once daily, and then titrated up to 5.0, 7.5, and 10.0 mg/day at 1-month intervals. The target maintenance dose was 10 mg/day. All adverse events were recorded during at least 3 months of follow-up. After 4-6 months of the titration protocol, only 18 patients (25.3%) reached and remained on ramipril 10 mg/day; 11 (15.5%), 22 (30.9%), and 20 patients (28.2%) remained on 2.5, 5.0, and 7.5 mg/day, respectively. Twenty-one patients (22.6%) had at least one adverse event. Twelve patients (13.0%) stopped treatment because of adverse effects. A total of 23 episodes of adverse events were reported, including cough (15.1%), dizziness (6.0%), and hypotension (2.4%). Ramipril was relatively well tolerated in our study population. However, only one-quarter of our patients reached the target maintenance dose of 10 mg/day. Dry cough, dizziness, and hypotension were the major side effects. About 15% of our patients discontinued ramipril treatment, which is comparable with previous reports.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Cough; Female; Humans; Male; Middle Aged; Patient Compliance; Ramipril; Risk

Cough is an important side effect of Angiotensin Converting Enzyme Inhibitor (ACEI) therapy. The incidence of cough was investigated in a prospective 8 week study in 250 hypertensive patients receiving ACEI alone or in combination with other agents. Enalapril (5-20 mg/day), Lisinopril (5-20 mg/day), Captopril (25-75 mg/day) or Ramipril (5-15 mg/day) was prescribed to patients, who were followed up at weekly visits. Cough developed in 73 of the 250 patients i.e. an incidence of 29.2%. Females had a higher incidence of cough as compared to males--37.9% versus 15.5% (p < 0.001) and there was no significant difference in the cough incidence in the various age groups. A dry, non-productive cough developed in all patients within 4 weeks of ACEI initiation. Increased nocturnal intensity of cough was reported by 79.4% patients. Cough incidence was 34.4%, 24.3% and 18.1% in patients on Enalapril, Ramipril and Lisinopril, respectively. Cough was not dose related and was not related to smoking. There was no statistically significant difference among patients on ACEI alone or in combination with beta blockers, calcium channel blockers or diuretics. Of the 18 patients with ACEI induced cough who received Indomethacin, 50 mg bid, 8 reported complete cure and cough was reduced in intensity in the remaining ten.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cough; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Incidence; India; Indomethacin; Lisinopril; Male; Middle Aged; Prospective Studies; Ramipril; Risk Assessment

OBJECTIVE. This study examines cough recorded in Prescription-Event Monitoring (PEM) of four ACE-inhibitors. Particular attention was paid to the study of enalapril because the drug was monitored before the causal relationship between cough and ACE-inhibitors had been widely accepted. RESULTS. Several factors which had obscured the causal relationship in the individual cases were found to be also an obstacle in PEM. For example, cough was a common and non-serious event and was under-reported in the PEM study of enalapril and the rate was not strikingly different from that recorded for other drugs. Cough induced by ACE-inhibitors has several characteristics which reduce the chance of a recognisable "signal'. The original questionnaires returned from doctors in the PEM study of enalapril have been reexamined. The observation that the rate of cough diminished after enalapril had been stopped rather than increased after starting, provided the best evidence of causality, because this was not affected by many biases such as the publicity that had occurred prior to doctors participating in PEM completed later reports.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cohort Studies; Cough; Enalapril; Female; Humans; Indoles; Lisinopril; Male; Middle Aged; Perindopril; Product Surveillance, Postmarketing; Ramipril; Structure-Activity Relationship; Surveys and Questionnaires

To evaluate the occurrence of asthma and dyspnoea precipitated or worsened by angiotensin converting enzyme inhibitors.. Summary of reports of adverse respiratory reaction in relation to treatment with angiotensin converting enzyme inhibitors that were submitted to Swedish Adverse Drug Reactions Advisory Committee and to World Health Organisation's international drug information system until 1992. Sales of angiotensin converting enzyme inhibitors in Sweden were also summarised.. Patients receiving angiotensin converting enzyme inhibitors who reported adverse respiratory reactions.. Clinical characteristics of adverse reactions of asthma, bronchospasm, and dyspnoea.. In Sweden 424 adverse respiratory reactions were reported, of which most (374) were coughing. However, 36 patients had adverse drug reactions diagnosed as asthma, bronchospasm, or dyspnoea. In 33 of these cases the indication for treatment with angiotensin converting enzyme inhibitors was hypertension, in only three heart failure. The respiratory symptoms occurred in about half of the patients within the first two weeks of treatment, and about one third needed hospitalisation or drug treatment. Dyspnoea symptoms occurred in conjunction with other symptoms from the airways or skin in 23 out of the 36 cases. In the WHO database there were 318 reports of asthma or bronchospasm, 516 reports of dyspnoea, and 7260 reports of cough in relation to 11 different angiotensin converting enzyme inhibitors.. Symptoms of airway obstruction in relation to treatment with angiotensin converting enzyme inhibitors seem to be a rare but potentially serious reaction generally occurring within the first few weeks of treatment.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Asthma; Bronchial Spasm; Captopril; Cough; Dyspnea; Enalapril; Female; Humans; Lisinopril; Male; Middle Aged; Ramipril