Treatment efficacy of anti-hypertensive drugs in monotherapy or combination (original) (raw)
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A Meta-Analytical Approach to the Efficacy of Antihypertensive Drugs in Reducing Blood Pressure
American Journal of Cardiovascular Drugs, 2005
the treatment of hypertension. The objective of this meta-analytical approach was to assess the efficacy of antihypertensive drugs most commonly used in France in reducing clinical SBP and DBP. Methods: The antihypertensive drugs selected were hydrochlorothiazide, indapamide sustained release (SR), furosemide and spironolactone for diuretics; amlodipine and lercanidipine for calcium channel antagonists; atenolol for ↑-adrenoceptor antagonists (↑-blockers); enalapril and ramipril for ACE inhibitors; and candesartan cilexetil, irbesartan, losartan, and valsartan for angiotensin II receptor antagonists. The trials selected were published between 1973 and 2004, evaluated monotherapy with trial drugs as fixed-dosage or with dosage increase, and assessed blood pressure reduction between 2 and 3 months. The analysis method used was based on the calculation of the sum weighted for the trial size. Results: A total of 72 trials (comprising 9094 patients) were selected and analyzed. No trial evaluating furosemide or spironolactone satisfied the inclusion criteria for this analysis. For SBP, the reduction was more marked with diuretics, calcium channel antagonists, and ACE inhibitors. Of all the drugs studied, indapamide SR gave the greatest SBP reduction (-22.2mm Hg). Evaluated therapeutic classes had a similar magnitude of effect on DBP, i.e. reduction between -11.4mm Hg with ↑-adrenoceptor antagonists and -10.3mm Hg with angiotensin II type 1 receptor antagonists. Conclusion: Indapamide SR 1.5mg appeared to be the most effective drug for a significant reduction in SBP within 2-3 months, which is an essential element in optimizing cardiovascular prevention among hypertensive patients. The clinical application of these results should take into consideration all the limitations discussed in this analysis.
Combination therapy in hypertension: An update
Diabetology & Metabolic Syndrome, 2010
Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensinaldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diureticbased. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females.
The Journal of Clinical Hypertension, 2008
Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow-up 4.9 years) by randomized groups: chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9,048), or lisinopril 10-40 mg/d (n=9,054) in a randomized double-blind hypertension trial. Participants were hypertensives age t55 with additional cardiovascular risk factor (s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mmHg (27% control) to 134/76 mmHg (chlorthalidone, 68% control), 135/75 mmHg (amlodipine, 66% control), and 136/76 mmHg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. A majority achieved BP control in each randomized group--a greater proportion with chlorthalidone.
Statistics in Medicine, 2013
The debate over whether certain antihypertensive medications have benefits beyond what would be expected from their blood pressure lowering spurred the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, which randomized 42,418 participants to chlorthalidone (15,255), amlodipine (9048), lisinopril (9054), or doxazosin (9061). We compared chlorthalidone, the active control, with each of the other three agents with respect to the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, and several other clinical endpoints. The arms were similar with respect to the primary endpoint, although some differences were found for other endpoints, most notably heart failure. Although the desire was to achieve similar blood pressure reductions in the four arms, we found some systolic blood pressure and diastolic blood pressure differences. A natural question is to what degree can observed treatment group differences in cardiovascular outcomes be attributed to these blood pressure differences. The purpose of this paper was to delineate the problems inherent in attempting to answer this question, and to present analyses intended to overcome these problems.
BMC Medicine, 2012
Background: We conducted a systematic review of evidence from randomized controlled trials to answer the following research question: What are the relative effects of different classes of antihypertensive drugs in reducing the incidence of cardiovascular disease outcomes for healthy people at risk of cardiovascular disease? Methods: We searched MEDLINE, EMBASE, AMED (up to February 2011) and CENTRAL (up to May 2009), and reference lists in recent systematic reviews. Titles and abstracts were assessed for relevance and those potentially fulfilling our inclusion criteria were then assessed in full text. Two reviewers made independent assessments at each step. We selected the following main outcomes: total mortality, myocardial infarction and stroke. We also report on angina, heart failure and incidence of diabetes. We conducted a multiple treatments meta-analysis using random-effects models. We assessed the quality of the evidence using the GRADE-instrument. Results: We included 25 trials. Overall, the results were mixed, with few significant dif-ferences, and with no drugclass standing out as superior across multiple outcomes. The only significant finding for total mortality based on moderate to high quality evidence was that beta-blockers (atenolol) were inferior to angiotensin receptor blockers (ARB) (relative risk (RR) 1.14; 95% credibility interval (CrI) 1.02 to 1.28). Angiotensin converting enzyme (ACE)inhibitors came out inferior to calcium-channel blockers (CCB) regarding stroke-risk (RR 1.19; 1.03 to 1.38), but superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94), both based on moderate quality evidence. Diuretics reduced the risk of myocardial infarction compared to beta-blockers (RR 0.82; 0.68 to 0.98), and lowered the risk of heart failure compared to CCB (RR 0.73; 0.62 to 0.84), beta-blockers (RR 0.73; 0.54 to 0.96), and alpha-blockers (RR 0.51; 0.40 to 0.64). The risk of diabetes increased with diuretics compared to ACE-inhibitors (RR 1.43; 1.12 to 1.83) and CCB (RR 1.27; 1.05 to 1.57).
Hypertension Research, 2005
had similar long-term efficacy and safety. Furthermore, we observed that in clinical trials in hypertensive or high-risk patients gradients in systolic blood pressure (SBP) accounted for most differences in outcome. To test whether our previous conclusions would hold, we updated our quantitative overview with new information from clinical trials published before 2005. To compare new and old antihypertensive drugs, we computed pooled odds ratios from stratified 2 ̱ 2 contingency tables. In a meta-regression analysis, we correlated these odds ratios with corresponding between-group differences in SBP. We then contrasted observed odds ratios with those predicted from gradients in SBP. The main finding of our overview was that reduction in SBP largely explained cardiovascular outcomes in the recently published actively controlled trials in hypertensive patients and in placebo-controlled secondary prevention trials. The published results suggested that dihydropyridine calcium-channel blockers might offer a selective benefit in the prevention of stroke and inhibitors of the renin-angiotensin system in the prevention of heart failure. For prevention of myocardial infarction, the published results were more equivocal, because of the benefit of amlodipine over placebo or valsartan in 2 trials, whereas other placebo-controlled trials of calcium-channel blockers or angiotensin converting enzyme inhibitors did not substantiate the expected benefit with regard to cardiac outcomes. In conclusion, the hypothesis that new antihypertensive drugs might influence cardiovascular prognosis over and beyond their antihypertensive effect remains unproven. Our overview emphasizes the need of tight blood pressure control, but does not allow determining to what extent blood pressure must be lowered for optimal cardiovascular prevention. ( Hypertens Res 2005; 28: 385-407)
Objective:To compare the therapeutic benefit of monotherapy and multiple therapy by assessing clinical outcome (BP measurement), To address and document the various adverse effects observed during monotherapy and multiple therapies for hypertensive patients, To compare the cost of both therapies during the treatment. Material and Methods:Two groups were included during the period of study, monotherapy and second group who received multiple therapy( dual therapy, triple therapy, quadruple therapy) ; Comparative study was done by measuring the outcome clinically by observing change in the BP. safety of the treatment regimen was assessed by observing the ADRs and cost comparison was carried out between the groups. ANOVA test was applied to check the statistical significance of the above mentioned parameters. Results: Out of total 200 patients, most of the patients (127) were females and the remaining (73) were males. Among 200 patients enrolled, 152 patients had hypertension along with other co morbidities and diabetes was the most common co morbid condition which was present in 126 patients. Most of patients were treated with monotherapy (96) which was followed by dual therapy (76). In monotherapy T.Furosemide reduced SBP by 50 mmHg and T.Nifedipine and T.Metoprolol Reduced DBP by 20 mmHg, whereas in dual therapy Inj. furosemide, T.Metoprolol decreased mean SBP by 60 mmHg and DBP by 40 mmHg respectively. Results showed that, triple drug therapy was most effective in reducing mean systolic (41.8-24%) and mean diastolic blood pressure (16.8-16.6%) and reduction of SBP by triple therapy was higher compared to other therapies. Conclusion: Combination therapy reduces both mean systolic and diastolic blood pressure compared to monotherapy. Triple drug therapy is more effective compared to dual and quadruple therapy. Pedal edema due to amlodipine is the most common ADR in both mono and multiple therapies. Combination therapy is more expensive than monotherapy, however triple therapy was most expensive compared to others.
Hypertension, 2001
Diuretics and -blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and ␣-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged Ն55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged Ն70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics? (Hypertension. 2001;37:19-27.)
Combined therapy in the treatment of hypertension: but which?
Journal of Hypertension, 2009
Hypertension is a major risk factor for cardiovascular disease. It has been estimated that the prevalence of hypertension is about 30% in general population and approximately two-thirds in elderly. This implies, for example, that 65 million people in the United States are hypertensives [1,2]. Blood pressure (BP) control is crucial to improve cardiovascular prognosis in hypertensive population [3]. Even small elevations above optimal BP values increase the likelihood of developing cardiovascular outcomes [3]. In Europe, BP control rates vary according to the country: in Italy about 31%, in United Kingdom 36%, in Germany and Spain 40% and in France 46% [1]. Although BP control is still far from optimal, in the last years it has markedly improved; thus, in Spain, BP control has increased from <20% in 90s to the current 40% [4]. However, taking into account that current European recommendations for the control of arterial hypertension have proposed more strict BP objectives (<130/80 mmHg) for patients at high or very high risk, such as those with stroke, myocardial infarction, diabetes mellitus, or renal dysfunction [3], it is very likely that the real control rates are lower. This is