Análisis crítico de un artículo: La suspensión de inhibidores de la bomba de protones induciría síntomas de reflujo / Critically appraised article

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

Safety and tolerability of ramipril 10 mg in patients at high risk of cardiovascular events: an observational study.

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.

Safety and tolerability of ramipril 10 mg in patients at high risk of cardiovascular events: an observational study.

OBJECTIVE: 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. METHODS: 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 artery disease and a history of cerebrovascular disease, peripheral arterial disease or diabetes (with microalbuminuria), 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 (o.d.) for a week, followed by 5 mg o.d. for 3 weeks and was then increased to 10 mg o.d. Data were analyzed using ANOVA and Chi square test. RESULTS: A total of 1,048 patients participated in this registry; 868 (82.87 percent;) continued with the treatment till the end of the registry (i.e., 8 weeks). At baseline, systolic BP was 130.1 +/- 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, 7.1% of patients had cough, which increased non-significantly to 10% 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. CONCLUSIONS: 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.

Effect of Ramipril, Valsartan, Candesartan and Lacidipine on inflammation and gastric ulcer in rats

The present study investigated and compared the effect of the angiotensin converting enzyme inhibitor ramipril and the angiotensin II receptor blockers valsartan and candesartan and the calcium channel blocker lacidipine on inflammation and gastric ulcer in rats. The acute inflammation was induced by intraplantar injection of carrageenan [1%] in the rat hind paw. Gastric ulcer was evoked by s.c. indomethacin [20 mg/kg]. When given s.c. 30 min prior to induction of inflammation, ramipril [0.23 and 0.45 mg/kg], valsartan [7.5 and 15 mg/kg], candesartan [0.72 and 1.44 gm/kg] failed to reduce paw oedema response. Meanwhile, lacidipine at the lower dose of 0.18 mg/kg displayed mild anti-inflammatory activity up to 1 hr, reducing paw odema by 26.7% for 1 hr post-carrageenan, while a higher dose of 0.36 mg/kg inhibited oedema formation by 33.5, 31, 23.6 and 22.3% at 1, 2, 3 and 4 hr post-carrageenan, respectively. The acute gastric mucosal lesions evoked by indomethacin in the rat were aggravated by co-administration of ramipril 0.23 and 0.45 mg/kg, valsartan 7.5 and 15 mg/kg, lacidipne 0.18 and 0.36 mg/kg and candesartan 0.72 mg/kg, but reduced by candesartan 1.44 mg/kg. Findings in the present study do not favor an anti-inflammatory activity for ramipril, valsartan and candesartan, but indicates an antioedema effect for lacidipine at the doses employed. These agents are likely to adversely affect gastric mucosal integrity and enhance the indomethacin-induced gastric injury

Angiotensin converting enzyme inhibitors and cough--a north Indian study.

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.

Eficacia clínica y aceptabilidad de ramipril en el tratamiento de la hipertensión arterial esencial etapas 1 y 2: resultados de un estudio multicéntrico / Clinical effectiveness and tolerance of ramipril in the treatment of essential arterial hypertension level 1 and 2: results of a multicentric study

One hundred eighty eight hyoertensive patients, aged 21 to 80 years old, coming from 4 Chilean hospitals were studied. Using an open non controlled design, they were treated with placebo for two weeks and with the active drug during eight weeks, in initial doses of 2.5 mg/day that were adjusted to 5 mg/day in diastolic blood pressure did not drop below 90 mm Hg or if its reduction was less than 10 mm Hg. During the active drug treatment period, systolic blood pressure decreased from 164.8ñ7.2 to 147.3ñ4.8 mm Hg. Diastolic blood pressure dropped from 102.3ñ3.1 to 87.8ñ3.0 mm Hg. Seventy percent of patients achieved a diastolic blood pressure of less than 90 mm Hg, 56.9 percent with 2.5 mg/day and 13.8 percent with 5 mg/day. Dizziness, cough and headache were the main adverse reactions, observed in 3.7, 3.2 and 2.1 percent of patients respectively. Adherence to treatment was 98 percent. There were no changes in laboratory values during the treatment period. Ramipril is effective and well tolerated in the treatment of essential hypertension

Ramipril vs captopril in mild to moderate hypertension.

Ramipril 5 mg once daily was compared to Captopril 50 mg twice daily in a randomised, double-blind, parallel group study in 60 patients with a diastolic blood pressure between 95 to 120 mmHg over a period of 2 months. Both drugs in the dose regimen used in this study exerted a similar anti-hypertensive effect at the end of 2 months of treatment resulting in a fall of supine diastolic blood pressure with Ramipril = 19.27 +/- 3.34 mmHg and Captopril = 19.15 +/- 2.63, in patients receiving the drugs without the diuretic. The mean fall in supine diastolic blood pressure 4 hours after the first dose of Ramipril was 6.5 mmHg and Captopril 8 mmHg. None of the patients developed first dose hypotension or orthostatic hypotension and there was no significant alteration of the heart rate in either group. The serum K+ levels remained unchanged in both groups of patients. Both drugs were well tolerated and there were no adverse effects observed on the liver, kidney, blood sugar or haemopoietic system. Based on the results of this study, it can be concluded that the antihypertensive efficacy of 5 mg ramipril in a once daily dose is equivalent to 50 mg captopril given twice daily. However an appreciably greater number of patients reported improvement in the "quality of life' parameters with ramipril as compared to captopril. Thus for the routine treatment of mild to moderate arterial hypertension, ramipril offers reliable antihypertensive efficacy in a once daily dose, thereby helping to improve patient compliance and making the treatment more economical.