RESUMO

BACKGROUND: Adherence to treatment after a myocardial infarction (MI) is poor, even in the early postinfarction period. Combining evidence-based drugs into a multicap could improve adherence in this population. No previous randomized trial assessing fixed-dose combination therapy has included patients early after a MI. We aimed to assess if a multicap containing four secondary prevention drugs increases adherence to treatment at 6 months after MI hospitalization. The study was designed as a randomized, parallel, open-label, controlled trial. METHODS: Patients were randomized within 7 days of a MI to either multicap or control group. The multicap group received a capsule containing aspirin, atenolol, ramipril, and simvastatin. The control group received each drug in separate pills. The primary outcome was adherence at 6 months. We also measured blood pressure, heart rate, serum cholesterol levels, C-reactive protein, and platelet aggregation. RESULTS: The study was stopped prematurely when 100 patients were included for futility. At 6 months, 92 (95.8%) patients were adherent to medical treatment: 98.0% in the multicap group and 93.5% in the control group [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.14; p = 0.347]. There were no differences between groups in systolic blood pressure (p = 0.662), diastolic blood pressure (p = 0.784), heart rate (p = 0.533), total cholesterol (p = 0.760), LDL-c (p = 0.979), C-reactive protein (p = 0.399), or in the proportion of patients with adequate platelet aggregation inhibition (p = 0.600). CONCLUSIONS: The study did not find any improvement in the adherence at 6 months after a MI with a multicap-based strategy (Multicap for Increase Adherence After Acute Myocardial Infarction; [ ClinicalTrials.gov identifier: NCT02271178]).

Assuntos

Síndrome Coronariana Aguda/terapia , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Aspirina/administração & dosagem , Atenolol/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adesão à Medicação , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Ramipril/administração & dosagem , Sinvastatina/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/fisiopatologia , Administração Oral , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Argentina , Aspirina/efeitos adversos , Atenolol/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Inibidores da Agregação Plaquetária/efeitos adversos , Ramipril/efeitos adversos , Prevenção Secundária , Sinvastatina/efeitos adversos , Comprimidos , Fatores de Tempo , Resultado do Tratamento

RESUMO

BACKGROUND: Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. OBJECTIVE: This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). METHODS: This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. RESULTS: A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant difference between groups in SBP and DBP during daytime or nighttime at the end of week 8. Office BP was significantly reduced in both treatment groups, with no significant differences between groups. The incidence of adverse events was 23.7% in group A and 21.7% in group B. CONCLUSIONS: Both treatment options were well tolerated and equally reduced BP. The results support the conclusion that group A (new fixed-dose combination of ramipril/HCTZ) was noninferior to group B (reference medication in Brazil). ISRCTN Register: ISRCTN05051235.

Assuntos

Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Ramipril/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Brasil , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ramipril/administração & dosagem , Ramipril/efeitos adversos , Fatores de Tempo , Resultado do Tratamento

RESUMO

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.

Assuntos

Humanos , Pessoa de Meia-Idade , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Benzimidazóis/efeitos adversos , Benzoatos/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Proteinúria/induzido quimicamente , Ramipril/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Taxa de Filtração Glomerular/efeitos dos fármacos , Estudos Multicêntricos como Assunto , Ramipril/administração & dosagem

RESUMO

BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS: The trial ran from 2001 to 2007. After a 3-week run-in period, 25,620 participants were randomly assigned to ramipril 10 mg a day (n = 8,576), telmisartan 80 mg a day (n = 8,542), or to a combination of both drugs (n = 8,502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n = 1,147 [13.4%]) and ramipril (1,150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1,233 [14.5%]; HR 1.09, 1.01-1.18, p = 0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%];HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24,1.01-1.51, p = 0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m² vs -4.12 [17.4], p < 0.0001) or combination therapy (-6.11 [17.9], p < 0.0001). The increase in urinary albumin excretion was less with telmisartan (p = 0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION: In people at high vascular risk, telmisartans effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

Assuntos

Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Benzimidazóis/efeitos adversos , Benzoatos/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Proteinúria/induzido quimicamente , Ramipril/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ramipril/administração & dosagem , Telmisartan

RESUMO

Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) >or=85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo ('missed dose') on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, P

Assuntos

Amidas/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fumaratos/administração & dosagem , Hipertensão/tratamento farmacológico , Adesão à Medicação , Ramipril/administração & dosagem , Tetrazóis/administração & dosagem , Adulto , Idoso , Amidas/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Monitorização Ambulatorial da Pressão Arterial , Brasil , Canadá , Método Duplo-Cego , Esquema de Medicação , Europa (Continente) , Feminino , Fumaratos/efeitos adversos , Humanos , Hipertensão/fisiopatologia , Irbesartana , Masculino , Pessoa de Meia-Idade , Ramipril/efeitos adversos , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento

RESUMO

We present the first reported case of untreatable hypoglycemia in a woman of 66-years-old, non-diabetic who received captopril for six years, and more recently ramipril. Six months ago, she was seen for the first time in our hospital. We found her disoriented, sweaty and confusing words frequently. Glucose tolerance test one hour after administration of glucose: 53 mg/dl. Test of insulin and C peptide had norms the same as the other contra-regulator hormones except glucagon with moderate elevation. The B.P. increased and we changed to ramipril, which improved the pressure but the hypoglycemia persisted. A new change was made to Losartan plus hydrochlorothiazide; after 72 hours patient improved. A new glucose tolerance test one hour after administration of glucose is absolutely normal. General conditions of the patients are observed more than 3 months and are asymptomatic. The B. P. is normal and we are keeping only the recently installed treatment.

Assuntos

Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Captopril/efeitos adversos , Hipertensão/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Ramipril/efeitos adversos , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Peptídeo C/sangue , Captopril/farmacologia , Captopril/uso terapêutico , Diuréticos , Quimioterapia Combinada , Feminino , Teste de Tolerância a Glucose , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/uso terapêutico , Hipoglicemia/diagnóstico , Insulina/sangue , Resistência à Insulina , Losartan/administração & dosagem , Losartan/uso terapêutico , Ramipril/farmacologia , Ramipril/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico

RESUMO

OBJECTIVE: To describe an episode of inadvertent and excessive anticoagulation caused by mistaken substitution of medication by a pharmacy outside the US. CASE SUMMARY: A 57-year-old white woman was found to have profound prolongation of her prothrombin time (56.9 sec) and international normalized ratio (22.18), with other coagulation parameters relatively normal. She had no prior history of bleeding diatheses and was not taking any prescribed anticoagulants. Her coagulopathy rapidly corrected with the administration of fresh frozen plasma and vitamin K. After her medications were visually inspected, it was discovered that she had purchased her prescription medications from a pharmacy in Mexico and that she inadvertently had been taking a preparation of warfarin (proprietary name in Mexico, "Romesa") instead of the prescribed ramipril for her hypertension (proprietary name in Mexico, "Ramace"). After removal of the incorrect medication, she experienced no further prolongation of her coagulation parameters. DISCUSSION: Medication errors contribute significantly to adverse events for patients. The frequency of different types of medication errors is reviewed, and problems specific to the use of warfarin are detailed. Circumstances that might lead to a patient seeking prescription medication outside of the US are also discussed. CONCLUSIONS: The acquisition of prescription medications from pharmacies outside of the US can have adverse consequences, especially if the foreign name of the medication is different from its American name, while sounding similar to other medications that also might be dispensed in foreign pharmacies.

Assuntos

Anticoagulantes/efeitos adversos , Erros de Medicação , Farmácias , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anticoagulantes/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Overdose de Drogas , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , México , Pessoa de Meia-Idade , Ramipril/efeitos adversos , Estados Unidos , Varfarina/efeitos adversos

RESUMO

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

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ramipril/farmacocinética , Hipertensão/tratamento farmacológico , Ramipril/efeitos adversos , Diástole/efeitos dos fármacos , Análise Química do Sangue , Protocolos Clínicos , Sístole