Integrated Blood Pressure Control[JOURNAL]
Sun
166 papers
The TRINITY Study: distribution of systolic blood pressure reductions.
Sugimoto DH, Chrysant SG, Melino M … +3 more , Lee J, Fernandez V, Heyrman R
Integr Blood Press Control · 2013 · PMID 23901293 · Full text
BACKGROUND: Elevated systolic blood pressure is more difficult to control than elevated diastolic blood pressure. The objective of this prespecified analysis of the Triple Therapy with Olmesartan Medoxomil, Amlodipine, a...
BACKGROUND: Elevated systolic blood pressure is more difficult to control than elevated diastolic blood pressure. The objective of this prespecified analysis of the Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY) was to compare the efficacy of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment with the component dual-combination treatments in reducing elevated seated systolic blood pressure (SeSBP). METHODS: The 12-week TRINITY study randomized participants to either one of the three component dual-combination treatments (OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg) or the triple-combination treatment. The primary outcome of this analysis was the categorical distribution of SeSBP reductions at week 12 from baseline with OM 40 mg/AML 10 mg/HCTZ 25 mg versus the dual-combination treatments. RESULTS: SeSBP reductions >50 mmHg were seen in 24.4% of participants receiving triple-combination treatment versus 8.1%-15.8% receiving dual-combination treatment. More participants receiving triple-combination treatment achieved the SeSBP target of <140 mmHg (73.6% versus 51.3%-58.8%; P < 0.001) and the seated blood pressure target of <140/90 mmHg (69.9% versus 41.1%-53.4%; P < 0.001). Prevalence and severity of adverse events were similar in all treatment groups. CONCLUSION: Treatment with OM 40 mg/AML 10 mg/HCTZ 25 mg was well tolerated and more effective in reducing SeSBP than the dual-combination treatments.
A review of the gastrointestinal therapeutic system (GITS) formulation and its effectiveness in the delivery of antihypertensive drug treatment (focus on nifedipine GITS).
Meredith PA, Elliott HL
Integr Blood Press Control · 2013 · PMID 23901292 · Full text
Hypertension treatment guidelines do not discriminate within drug classes and, furthermore, do not consider whether or not all of the formulations of any given drug licensed for once-daily administration can be considere...
Hypertension treatment guidelines do not discriminate within drug classes and, furthermore, do not consider whether or not all of the formulations of any given drug licensed for once-daily administration can be considered to be therapeutically interchangeable. This article focuses on this issue with respect to nifedipine and the development of the gastrointestinal therapeutic system (GITS) formulation. Nifedipine GITS is regarded as the gold standard once-daily formulation of nifedipine and, as such, it is anticipated that alternative formulations will be therapeutically equivalent to nifedipine GITS. In general, this depends on demonstrating pharmacokinetic bioequivalence. This article is intended to focus attention on generic substitution and, in particular, on aspects of the scientific basis for the substitution of generic products in place of branded products. Such substitution is required for cost-saving or cost-containment reasons and is justified on the basis that the generic (substitute) drug is "therapeutically" equivalent to the branded drug. Unfortunately, there are serious shortcomings in the current methods of assessment insofar as they are typically based on statistical comparisons of average pharmacokinetic parameter values, using arbitrary comparative criteria. This article illustrates the shortcomings of the current approaches to generic substitution and concludes that, in regulatory terms, either more rigorous pharmacokinetic criteria are required or pharmacodynamic indices should be added to reinforce the regulatory criteria. Generic substitution is a balancing act but, at the moment, the cost issue is dominant. To restore the balance, equivalent efficacy must be confirmed. At present, therefore, in the absence of such regulatory rigor, the obvious course is to prefer the branded product, the therapeutic efficacy of which (including outcome benefits) has been established.
Current perspectives on combination therapy in the management of hypertension.
Mallat SG, Itani HS, Tanios BY
Integr Blood Press Control · 2013 · PMID 23837009 · Full text
Hypertension (HTN) is a worldwide health problem and a major preventable risk factor for cardiovascular (CV) events. Achieving an optimal blood pressure (BP) target for patients with HTN will often require more than one...
Hypertension (HTN) is a worldwide health problem and a major preventable risk factor for cardiovascular (CV) events. Achieving an optimal blood pressure (BP) target for patients with HTN will often require more than one BP-lowering drug. Combination therapy is not only needed, but also confers many advantages such as better efficacy and a better tolerability. A better compliance and simplicity of treatment is noted with the single-pill combination (SPC). In addition, for those patients who do not achieve BP target when receiving dual combinations, triple SPCs are now available, and their efficacy and safety have been tested in large clinical trials. BP-lowering drugs used in combination therapy should have complementary mechanisms of action, leading to an additive BP-lowering effect and improvement in overall tolerability, achieved by decreasing the incidence of adverse effects. On the basis of large, outcome-driven trials, preferred dual combinations include an angiotensin receptor antagonist (ARB) or an angiotensin converting enzyme inhibitor (ACEI) combined with a calcium channel blocker (CCB), or an ARB or ACEI combined with a diuretic. Acceptable dual combinations include a direct rennin inhibitor (DRI) and a CCB, a DRI and a diuretic, a beta-blocker and a diuretic, a CCB and a diuretic, a CCB and a beta-blocker, a dihydropyridine CCB and a non-dihydropyridine CCB, and a thiazide diuretic combined with a potassium-sparing diuretic. Some combinations are not recommended and may even be harmful, such as dual renin angiotensin aldosterone system inhibition. Currently available triple SPCs combine a renin angiotensin aldosterone system inhibitor with a CCB and a diuretic. Combination therapy as an initial approach is advocated in patients with a systolic BP more than 20 mmHg and/or a diastolic BP more than 10 mmHg above target and in patients with high CV risk. In addition, using SPCs has been stressed and favored in recent international guidelines. Recently, triple SPCs have been approved and provide an attractive option for patients not achieving BP target on dual combination. The effect of such a strategy in the overall management of HTN, especially on further reducing the incidence of CV events, will have to be confirmed in future clinical and population-based studies.
Optimizing combination therapy in the management of hypertension: the role of the aliskiren, amlodipine, and hydrochlorothiazide fixed combination.
Hovater MB, Jaimes EA
Integr Blood Press Control · 2013 · PMID 23837008 · Full text
High blood pressure is the leading risk factor for death and disability worldwide, and the prevalence is increasing. Effective treatment decreases the risk of adverse events in proportion to blood pressure reduction. Com...
High blood pressure is the leading risk factor for death and disability worldwide, and the prevalence is increasing. Effective treatment decreases the risk of adverse events in proportion to blood pressure reduction. Combination antihypertensive therapy reduces blood pressure promptly and effectively. Single-pill combinations reduce the pill burden and improve adherence, efficacy, and tolerability of treatment compared with single drug pills. A significant portion of the hypertensive population will require three drugs for adequate control. The single-pill combination of aliskiren, amlodipine, and hydrochlorothiazide is based on complementary mechanisms of action. Clinical trials have shown it to be a safe and effective treatment for hypertension. This combination is a reasonable choice in clinical practice for patients with hypertension that requires three drugs for effective treatment.
Long-acting nifedipine for hypertensive patients in the Middle East and Morocco: observations on efficacy and tolerability of monotherapy or combination therapy.
Ghoneim RA, Omar AK, Sebastian V … +4 more , Kassab R, Akijian G, Hafiz M, Schmidt B
Integr Blood Press Control · 2013 · PMID 23807860 · Full text
BACKGROUND: The Middle Eastern and North African region of developing countries is associated with poor rates of blood pressure (BP) control and antihypertensive prescribing patterns. This post hoc analysis of data from...
BACKGROUND: The Middle Eastern and North African region of developing countries is associated with poor rates of blood pressure (BP) control and antihypertensive prescribing patterns. This post hoc analysis of data from an international observational study aimed to investigate the efficacy and tolerability of long-acting nifedipine (30 mg or 60 mg; monotherapy or in combination) in the Middle Eastern and Moroccan populations defined as having high cardiovascular risk. METHODS: This was a prospective, noninterventional, multicenter observational study. Observations from patients (aged ≥ 18 years) with treated or untreated hypertension from the Middle East (Jordan, Saudi Arabia, Kuwait, Lebanon, Qatar, United Arab Emirates, and Yemen) and Morocco are presented. Hypertension grade and cardiovascular risk were defined at baseline, and systolic/diastolic BP change was defined at post-baseline visits (≤3). Adverse events and ratings of therapy efficacy and patient/physician satisfaction were recorded. RESULTS: The study included 1466 patients from the Middle East and 524 from Morocco. Characteristics of the populations differed, with a more severe hypertension profile in Moroccan patients. Despite these differences, nifedipine reduced BP to a similar extent in each group, with efficacy dependent on cardiovascular risk factors such as hypertension grade and age. Few adverse drug reactions occurred and nifedipine was well-tolerated in both populations. Efficacy and satisfaction with therapy were rated highly. CONCLUSION: Good rates of BP control were observed with nifedipine in patients with moderate-to-severe hypertension and high added risk. Published data in these countries suggest poor antihypertensive prescribing patterns and BP control; these data confirm this trend and suggest that suboptimal dosing may be prevalent.
Azilsartan/chlorthalidone combination therapy for blood pressure control.
Cheng JW
Integr Blood Press Control · 2013 · PMID 23807859 · Full text
BACKGROUND: Edarbyclor(®) is a combined angiotensin receptor blocker (ARB) and thiazide-like diuretic (azilsartan and chlorthalidone), and was approved on December 20, 2011 by the US Food and Drug Administration (FDA) fo...
BACKGROUND: Edarbyclor(®) is a combined angiotensin receptor blocker (ARB) and thiazide-like diuretic (azilsartan and chlorthalidone), and was approved on December 20, 2011 by the US Food and Drug Administration (FDA) for hypertension management. OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, tolerability, and role of azilsartan plus chlorthalidone for hypertension management. METHODS: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines, were identified from the databases MEDLINE and Current Contents (both 1966 to February 15, 2013, inclusive) using search terms "azilsartan", "chlorthalidone", "pharmacology", "pharmacokinetics", "pharmacodynamics", "pharmacoeconomics", and "cost-effectiveness". The FDA website, as well as manufacturer prescribing information, was also reviewed to identify other relevant information. RESULTS: Azilsartan is a new ARB with high affinity for the angiotensin 1 receptor, approved by the FDA for hypertension management. Unlike other ARBs, azilsartan has no clinical data supporting improvement in cardiovascular outcomes, and is not approved for indications other than hypertension, which a select few other ARBs may be used for (eg, diabetic nephropathy and heart failure). Chlorthalidone is a longer acting thiazide-like diuretic that has been demonstrated to improve cardiovascular outcomes. Combination treatment with azilsartan/chlorthalidone is effective for reducing blood pressure. Compared to olmesartan/hydrochlorothiazide and azilsartan/hydrochlorothiazide combinations, azilsartan/chlorthalidone appears to be more efficacious for reducing blood pressure. CONCLUSIONS: Azilsartan/chlorthalidone can be considered an antihypertensive therapy option in patients for whom combination therapy is required (blood pressure >20 mmHg systolic or >10 mmHg diastolic above goal). Cost to patients and insurance coverage will probably determine whether azilsartan/chlorthalidone will be the most appropriate combination therapy for an individual patient.
Cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness.
Sun CK
Integr Blood Press Control · 2013 · PMID 23667317 · Full text
Arterial stiffness has been identified as an independent predictor of prognostic outcomes for patients with cardiovascular disease. Although measurement of pulse wave velocity has been a widely accepted noninvasive appro...
Arterial stiffness has been identified as an independent predictor of prognostic outcomes for patients with cardiovascular disease. Although measurement of pulse wave velocity has been a widely accepted noninvasive approach to the assessment of arterial stiffness, its accuracy is hampered by changes in blood pressure. Taking the exponential relation between intravascular pressure and arterial diameter into consideration, a stiffness parameter can be obtained by plotting the natural logarithm of systolic-diastolic pressure ratio against the arterial wall extensibility. Cardio-ankle vascular index (CAVI), which is calculated based on the stiffness parameter thus obtained, is theoretically independent of changes in blood pressure. With this distinct advantage, CAVI has been widely applied clinically to assess arterial stiffness in subjects with known cardiovascular diseases including those with diagnosed atherosclerosis, coronary heart disease, and stroke as well as those at risk, including those with hypertension, diabetes, the elderly, and the obese. Because of its enhanced sensitivity, not only has the index been used to discern subtle changes in the disease process, it has also been utilized in studying normal individuals to assess their potential risks of developing cardiovascular diseases. The primary aims of assessing arterial stiffness using CAVI are not only to aid in early detection of arteriosclerosis to allow timely treatment and change in lifestyle, but also to quantitatively evaluate the progression of disease and the effectiveness of treatment. Despite its merit of being unaffected by blood pressure, discretion in data interpretation is suggested because an elevated CAVI represents not just vascular stiffness caused by pathological changes in the arterial wall, but can also be attributed to an increased vascular tone brought about by smooth muscle contraction. Moreover, certain patient populations, such as those with an ankle-brachial index < 0.9, may give falsely low CAVI and are suggested to be excluded from study.
Current Perspectives on rosuvastatin.
Hu M, Tomlinson B
Integr Blood Press Control · 2013 · PMID 23637557 · Full text
Rosuvastatin is one of the most potent statins available for reducing circulating low-density lipoprotein cholesterol (LDL-C) levels, which enables more high-risk patients to achieve their lipid goals. Its favorable bala...
Rosuvastatin is one of the most potent statins available for reducing circulating low-density lipoprotein cholesterol (LDL-C) levels, which enables more high-risk patients to achieve their lipid goals. Its favorable balance of effects on atherogenic and protective lipoproteins and its pleiotropic effects, including anti-inflammatory and antioxidant effects and improvement in endothelial dysfunction, are associated with slowing of progression of atherosclerosis within the artery wall and have been translated into clinical benefits for cardiovascular outcomes. This review provides an update on the safety and the efficacy of rosuvastatin in recent large clinical trials. It appears that rosuvastatin has a beneficial effect on the progression of atherosclerosis across the clinical dosage range of 2.5-40 mg. It reduced cardiovascular events in relatively low-risk subjects with elevated high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol. As with other statins, rosuvastatin did not show overall benefit in terms of survival in patients with heart failure, but certain clinical or biochemical markers reflecting underlying disease characteristics may help to identify subgroups of patients that benefit from statin therapy. In patients with end-stage renal disease undergoing chronic hemodialysis, rosuvastatin had no effect on reducing cardiovascular events. Although there is a slightly increased risk of incident diabetes with this class of agents, the absolute benefits of statin therapy on cardiovascular events overweigh the risk in patients with moderate or high cardiovascular risk or with documented cardiovascular disease. As with other statins, rosuvastatin is an appropriate therapy in addition to antihypertensive treatment to reduce cardiovascular risk in hypertensive patients.
Efficacy and tolerability of a single-pill combination of telmisartan 80 mg and hydrochlorothiazide 25 mg according to age, gender, race, hypertension severity, and previous antihypertensive use: planned analyses of a randomized trial.
Zhu D, Bays H, Gao P … +3 more , Mattheus M, Voelker B, Ruilope LM
Integr Blood Press Control · 2013 · PMID 23637556 · Full text
BACKGROUND: The purpose of this work was to describe the efficacy and safety of a telmisartan 80 mg + hydrochlorothiazide 25 mg (T80/H25) single-pill combination therapy in patients with moderate-severe hypertension (mea...
BACKGROUND: The purpose of this work was to describe the efficacy and safety of a telmisartan 80 mg + hydrochlorothiazide 25 mg (T80/H25) single-pill combination therapy in patients with moderate-severe hypertension (mean seated trough cuff systolic blood pressure [BP] ≥ 160 mmHg and diastolic BP ≥ 100 mmHg) in specific patient subpopulations. METHODS: This was a planned analysis of a double-blind, multicenter, parallel-group trial that demonstrated the superiority of a single-pill combination of T80/H25 versus T80 monotherapy in terms of systolic BP change from baseline to week 7. Subpopulations included older (aged ≥ 65 years) versus younger, gender, race, hypertension severity, and prior antihypertensive therapy. Endpoints were change from baseline in mean seated trough cuff systolic and diastolic BP, proportion of patients achieving their BP goal (systolic/diastolic BP < 140/90 mmHg), and proportion of patients attaining systolic BP reductions of >30 mmHg and >40 mmHg. RESULTS: Across all subgroups, the T80/H25 single-pill combination provided consistently greater systolic and diastolic BP reductions than T80 and more patients had systolic BP reductions of >30 mmHg. In the T80 and T80/H25 groups, BP control was achieved in 34.1% and 48.8% of men, 35.5% and 62.7% of women, 34.5% and 56.6% of Asians, 22.6% and 38.6% of blacks, 36.7% and 57.8% of whites, 36.9% and 57.5% of patients < 65 years, 29.3% and 49.3% ≥65 years, 44.2% and 66.2% of those with grade 2 hypertension, 20.4% and 39.4% of those with grade 3 hypertension, 38.9% and 53.2% of previously untreated patients, 38.1% and 62.5% of patients previously treated with one antihypertensive, and 29.7% and 48.9% of patients previously treated with two or more antihypertensive agents respectively. Treatment was generally well tolerated across the patient subgroups. CONCLUSION: The T80/H25 single-pill combination provides consistent BP reductions and higher goal attainment rates versus T80 across a range of hypertensive patient subgroups, which are likely to have a positive impact on patients' cardiovascular risk.
Out-of-office blood pressure: from measurement to control.
Baguet JP
Integr Blood Press Control · 2012 · PMID 22654523 · Full text
Hypertension is an important risk factor for the development of cardiovascular disease, and is a major cause of morbidity and mortality worldwide. Traditionally, hypertension diagnosis and treatment and clinical evaluati...
Hypertension is an important risk factor for the development of cardiovascular disease, and is a major cause of morbidity and mortality worldwide. Traditionally, hypertension diagnosis and treatment and clinical evaluations of antihypertensive efficacy have been based on office blood pressure (BP) measurements; however, there is increasing evidence that office measures may provide inadequate or misleading estimates of a patient's true BP status and level of cardiovascular risk. The introduction, and endorsement by treatment guidelines, of 24-hour ambulatory BP monitoring and self (or home) BP monitoring has facilitated more reliable and reproducible estimations of true BP, including the identification of white-coat and masked hypertension, and evaluation of BP variability. In addition, ambulatory BP monitoring enables accurate assessment of treatment effectiveness over 24 hours and both ambulatory and self BP monitoring may lead to better tailoring of therapy according to BP profile and concomitant disease. This review describes the clinical benefits and limitations of out-of-office assessments and their applications for effective management of hypertension and attainment of BP control.
New treatment options in the management of hypertension: appraising the potential role of azilsartan medoxomil.
Volpe M, Savoia C
Integr Blood Press Control · 2012 · PMID 22457601 · Full text
Renin-angiotensin-system (RAS) activation plays a key role in the development of hypertension and cardiovascular disease. Drugs that antagonize the RAS (angiotensin-converting enzyme [ACE] inhibitors and angiotensin rece...
Renin-angiotensin-system (RAS) activation plays a key role in the development of hypertension and cardiovascular disease. Drugs that antagonize the RAS (angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]) have proven clinical efficacy in reducing blood pressure values and cardiovascular morbidity and mortality. ACE inhibitors partially inhibit plasma ACE, and angiotensin II generation. Thus, ARBs, which block selectively type 1 angiotensin II receptor (AT(1)R), have been developed and used in the clinical management of hypertension and cardiovascular disease. Experimental and clinical trials with ARBs indicate that this class of drug represents an effective, safe and well tolerated therapeutic option for the prevention and care of hypertension, even though there is no proven superiority as compared to ACE inhibitors except for the better tolerability. Most ARBs may not completely inhibit the AT(1)R at the approved clinical doses. Azilsartan medoxomil is a newly approved ARB for the management of hypertension. This ARB induces a potent and long-lasting antihypertensive effect and may have cardioprotective properties. This article reviews the current evidence on the clinical effectiveness of azilsartan in hypertension.
Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials.
Lemoine P, Wade AG, Katz A … +2 more , Nir T, Zisapel N
Integr Blood Press Control · 2012 · PMID 22346363 · Full text
BACKGROUND: Add-on prolonged-release melatonin (PRM) in antihypertensive therapy has been shown to ameliorate nocturnal hypertension. Hypertension is a major comorbidity among insomnia patients. The efficacy and safety o...
BACKGROUND: Add-on prolonged-release melatonin (PRM) in antihypertensive therapy has been shown to ameliorate nocturnal hypertension. Hypertension is a major comorbidity among insomnia patients. The efficacy and safety of PRM for primary insomnia in patients aged 55 years and older who are treated with antihypertensive drugs were evaluated. METHODS: Post hoc analysis of pooled antihypertensive drug-treated subpopulations from four randomized, double-blind trials of PRM and placebo for 3 weeks (N[PRM] = 195; N[placebo] = 197) or 28 weeks (N[PRM] = 157; N[placebo] = 40). Efficacy measurements included Leeds Sleep Evaluation Questionnaire scores of quality of sleep and alertness and behavioral integrity the following morning after 3 weeks, and sleep latency (daily sleep diary) and Clinical Global Impression of Improvement (CGI-I) after 6 months of treatment. Safety measures included antihypertensive drug-treated subpopulations from these four and three additional single-blind and open-label PRM studies of up to 1 year (N[PRM] = 650; N[placebo] = 632). RESULTS: Quality of sleep and behavior following wakening improved significantly with PRM compared with placebo (P < 0.0001 and P < 0.0008, respectively). Sleep latency (P = 0.02) and CGI-I (P = 0.0003) also improved significantly. No differences were observed between PRM and placebo groups in vital signs, including daytime blood pressure at baseline and treatment phases. The rate of adverse events normalized per 100 patient-weeks was lower for PRM (3.66) than for placebo (8.53). CONCLUSIONS: The findings demonstrate substantive and sustained efficacy of PRM in primary insomnia patients treated with antihypertensive drugs. PRM appears to be safe for insomnia in patients with cardiovascular comorbidity.
Cardio classics revisited: focus on the role of amlodipine.
Owen AJ, Reid CM
Integr Blood Press Control · 2012 · PMID 22346362 · Full text
Amlodipine is a long-acting, dihydropyridine calcium antagonist now widely used for lowering of elevated blood pressure. In recent years it has been shown to be effective in reducing both blood pressure and risk of cardi...
Amlodipine is a long-acting, dihydropyridine calcium antagonist now widely used for lowering of elevated blood pressure. In recent years it has been shown to be effective in reducing both blood pressure and risk of cardiovascular (CV) events when used in combination with other antihypertensive agents of different classes. Strong evidence of cardiovascular benefit has been attained for combination of amlodipine with diuretics or angiotensin converting enzyme (ACE) inhibitors in a number of high-risk CV groups, including those with established coronary artery disease, diabetes, and at risk of renal disease. Combination therapies of amlodipine with other agents eliciting renin-angiotensin-aldosterone system blockade (angiotensin II receptor blockers or renin inhibitors) have been shown to be effective blood pressure-lowering strategies, but await the results of ongoing trials for direct evidence of benefit for renal disease progression and CV morbidity and mortality.
Integrated control of hypertension by olmesartan medoxomil and hydrochlorothiazide and rationale for combination.
Punzi HA
Integr Blood Press Control · 2011 · PMID 22253546 · Full text
Hypertension affects nearly one-third of all individuals in the US, yet one-half of all treated patients achieve blood pressure (BP) controlled to recommended goals. The percentage of patients with uncontrolled BP is lik...
Hypertension affects nearly one-third of all individuals in the US, yet one-half of all treated patients achieve blood pressure (BP) controlled to recommended goals. The percentage of patients with uncontrolled BP is likely to be much higher when considering the number of patients who are not even aware of their hypertensive state. Elevated BP is associated with increased risks of cardiovascular events and end-organ damage. Antihypertensive monotherapy is not always sufficient to achieve BP goals, and thus more aggressive treatment regimens need to be considered. Antihypertensive combination therapy, which may improve tolerability, offers the benefit of targeting different mechanisms of action. Numerous outcomes studies support the use of a renin-angiotensin system inhibitor as a first-line choice in antihypertensive therapy. This review discusses the benefits of combination therapy with the angiotensin type II receptor blocker olmesartan medoxomil (OM) paired with the thiazide diuretic hydrochlorothiazide (HCTZ). The pharmacokinetic properties of OM will be reviewed in addition to efficacy studies that support OM + HCTZ combination therapy over other possible antihypertensive combinations. Finally, a rationale for choosing HCTZ over another diuretic, chlorthalidone, will also be discussed based on pharmacokinetic differences, clinical concerns, and trends in use.
Combining antihypertensive and antihyperlipidemic agents - optimizing cardiovascular risk factor management.
Zamorano J, Edwards J
Integr Blood Press Control · 2011 · PMID 22162939 · Full text
Clinical guidelines now recognize the importance of a multifactorial approach to managing cardiovascular (CV) risk. This idea was taken a step further with the concept of the Polypill™. There are, however, considerable p...
Clinical guidelines now recognize the importance of a multifactorial approach to managing cardiovascular (CV) risk. This idea was taken a step further with the concept of the Polypill™. There are, however, considerable patent, pharmacokinetic, pharmacodynamic, registration, and cost implications that will need to be overcome before the Polypill™ or other single-pill combinations of CV medications become widely available. However, a medication targeting blood pressure (BP) and lipids provides much of the proposed benefits of the Polypill™. A single-pill combination of the antihypertensive amlodipine besylate and the lipid-lowering medication atorvastatin calcium (SPAA) is currently available in many parts of the world. This review describes the rationale for this combination therapy and the clinical trials that have demonstrated that these two agents can be combined without the loss of efficacy for either agent or an increase in the incidence of adverse events. The recently completed Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial) is discussed in detail. CRUCIAL was a 12-month, international, multicenter, prospective, open-label, parallel design, cluster-randomized trial, which demonstrated that a proactive intervention strategy based on SPAA in addition to usual care (UC) had substantial benefits on estimated CV risk, BP, and lipids over continued UC alone. Adherence with antihypertensive and lipid-lowering therapies outside of the controlled environment of clinical trials is very low (~30%-40% at 12 months). Observational studies have demonstrated that improving adherence to lipid-lowering and antihypertensive medications may reduce CV events. One means of improving adherence is the use of single-pill combinations. Real-world observational studies have demonstrated that patients are more adherent to SPAA than co-administered antihypertensive and lipid-lowering therapy, and this improved adherence translated to reduced CV events. Taken together, these findings suggest that SPAA can play an important role in helping physicians improve the management of CV risk in their patients.
Challenges posed to the maternal circulation by pregnancy.
Valdés G, Corthorn J
Integr Blood Press Control · 2011 · PMID 22162938 · Full text
In primates, adequate growth of the fetus depends on the development of the uteroplacental unit. On the fetal side, this is achieved by the creation of the vascular network of the placenta. On the maternal side, the tran...
In primates, adequate growth of the fetus depends on the development of the uteroplacental unit. On the fetal side, this is achieved by the creation of the vascular network of the placenta. On the maternal side, the transformation of the spiral arteries into saccular nonreactive vessels by the trophoblast provides high blood flow to the intervillous space. Apart from the changes in the uterine arteries, the mother expands her plasma volume - at the expense of stimulating the renin-angiotensin-aldosterone system - and her cardiac output. In the maintaining of normotension in the face of an increased cardiac output and plasma volume, the renin-angiotensin-aldosterone system requires an enhanced vasodilator synthesis. Finally, in the late stages of pregnancy, a normal endothelial function is required to provide an ample margin to the activation provoked by deportation of syncytiotrophoblast fragments/factors to the maternal circulation. These four adaptative processes require various interrelated vasodilator systems. Deficient adaptations cause isolated or proteinuric arterial hypertension, intrauterine growth restriction, preterm delivery, and stillbirths, among others. Moreover, a normal or a defective adaptation to pregnancy influences maternal cardiovascular health in later life, as evidenced by various studies, most of them epidemiological; thus, pregnancy is now considered a stress test to the maternal cardiovascular system. Because of this, women planning to become pregnant should be screened for clinical and biochemical cardiovascular risks. Inversely, women presenting with hypertension in pregnancy should be thoroughly studied to detect and correct cardiovascular risks. The incorporation of the predictive value of a hypertensive pregnancy should help reduce cardiovascular disease in women.
Short- and long-term physiologic and pharmacologic control of blood pressure in pediatric patients.
Trachtman H
Integr Blood Press Control · 2011 · PMID 21949637 · Full text
The incidence of hypertension is rising in the general population. A parallel trend is present in children and adolescents. This reflects more intensive treatment and improved patient survival after a wide range of serio...
The incidence of hypertension is rising in the general population. A parallel trend is present in children and adolescents. This reflects more intensive treatment and improved patient survival after a wide range of serious systemic illnesses that can lead to hypertension. In addition, primary or essential hypertension is more prevalent because of the epidemic of obesity and metabolic syndrome in pediatric and adult patients of both genders and in all ethnic groups. As a consequence of the changing demographic pattern of hypertension, more patients are requiring therapy for elevated blood pressure. This review summarizes key aspects of the treatment for hypertension in pediatric patients and the long-term management of this problem, including nonpharmacologic strategies and drug treatment.
Clinical utility of fixed-combination telmisartan-amlodipine in the treatment of hypertension.
Segura J, Ruilope LM
Integr Blood Press Control · 2011 · PMID 21949636 · Full text
The majority of hypertensive patients, especially those with target organ damage, are likely to require multiple-drug therapy in order to reach blood pressure (BP) targets and reduce their risk of adverse vascular outcom...
The majority of hypertensive patients, especially those with target organ damage, are likely to require multiple-drug therapy in order to reach blood pressure (BP) targets and reduce their risk of adverse vascular outcomes. The rationale for combination therapy with agents that block the renin-angiotensin system (RAS) and a calcium channel blocker (CCB) or diuretic is well founded in growing evidence. Recent published trials have shown that the combination of an RAS suppressor and a dihydropiridinic CCB would offer additional benefits independently of BP reduction. A telmisartan-amlodipine combination has demonstrated significantly greater BP reductions compared with each monotherapy component in the overall population, and in particular in patients with moderate to severe hypertension and high-risk patients. This combination is well tolerated with a safety profile similar to placebo and is consistent with the known safety profile of its monotherapy components.
Long-term use and tolerability of irbesartan for control of hypertension.
Forni V, Wuerzner G, Pruijm M … +1 more , Burnier M
Integr Blood Press Control · 2011 · PMID 21949635 · Full text
In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hyp...
In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150-300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics.
Hypertension and other morbidities with Cushing's syndrome associated with corticosteroids: a review.
Peppa M, Krania M, Raptis SA
Integr Blood Press Control · 2011 · PMID 21949634 · Full text
Corticosteroids constitute an ideal treatment for various inflammatory and autoimmune disorders due to their anti-inflammatory and immunomodulatory actions. However, corticosteroids have a considerable number of side eff...
Corticosteroids constitute an ideal treatment for various inflammatory and autoimmune disorders due to their anti-inflammatory and immunomodulatory actions. However, corticosteroids have a considerable number of side effects, including hypertension, diabetes, lipid disorders, sleep apnea, osteoporosis, myopathy, and disorders of coagulation and fibrinolysis, which are components of Cushing's syndrome (CS). Corticosteroid-induced side effects are dependent on the formulation, route, dose, and time of exposure. However, the underlying pathogenetic mechanisms have not been clearly defined. A large body of evidence supports the role of an imbalance between vasoconstriction and vasodilation with possible links to nitric oxide, prostanoids, angiotensin II, arginine vasopressin, endothelins, catecholamines, neuropeptide Y, and atrial natriuretic peptide. Increased oxidative stress, renin-angiotensin system activation, increased pressor response, metabolic syndrome, and sleep apnea appear to be pathogenetically involved as well. The ideal treatment is the withdrawal of corticosteroids, which is most often impossible due to the exacerbation of the underlying disease. Alternatively, a careful plan, including the proper selection of the formulation, time, and route, should be made, and each side effect should be treated properly. The focus of the research should be to develop synthetic corticosteroids with anti-inflammatory effects but fewer metabolic effects, which so far has been unsuccessful.
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