Instructions for use ALLOPURINOL
The use of the drug by patients with renal failure, as well as with hematopoietic disorders, should be under constant medical supervision.
Skin reactions are the most common reactions and can occur at any time during treatment; if they occur, allopurinol should be discontinued immediately. After symptoms have reduced, the drug can be prescribed in low doses (for example, 50 mg / day), gradually increasing the dose if necessary. If the skin rash recurs, the drug should be discontinued permanently, as severe generalized hypersensitivity reactions may occur.
There have been reports of life-threatening skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) with the use of allopurinol. Patients should be informed of the signs and symptoms of skin reactions and monitored closely. The highest risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis is during the first weeks of treatment.
If signs or symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis occur (eg, progressive skin rash, often with blisters, or mucosal lesions), Allopurinol 100 mg tablets should be discontinued immediately.
The best results in the treatment of Stevens-Johnson syndrome or toxic epidermal necrolysis have been obtained with early diagnosis and immediate discontinuation of the suspected drug. Early discontinuation of Allopurinol 100 mg tablets is associated with a better prognosis.
If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking Allopurinol, 100 mg tablets, the use of Allopurinol, 100 mg tablets should not be resumed.
Vasculitis and tissue reactions associated with hypersensitivity reactions can have various manifestations, incl. hepatitis, kidney damage (interstitial nephritis) and, very rarely, seizures. These reactions can occur at any time during treatment; if they occur, the drug should be discontinued immediately.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
During the period of use of Allopurinol, it is necessary to refrain from driving vehicles and other mechanisms due to the possibility of dizziness or drowsiness.
Introduction
Gout is the most common inflammatory arthritis in adults [1], the prevalence of which has continued to increase over the past decades [2, 3].
The main goal of gout treatment is to achieve and long-term maintenance of target uric acid (UA) levels through the use of both drug and non-drug therapies. And although the fundamental principles of gout therapy have remained unshakable over the past decades, the development of medicine and the accumulated clinical experience suggest the need for constant correction of existing recommendations.
The article highlights some controversial issues in the treatment of gout that have been discussed in recent years.
Use of urate-lowering therapy during an acute attack of arthritis
The question of when therapy should be prescribed has never been widely discussed in the literature; however, it is generally accepted that urate-lowering drugs should be initiated only after complete relief of arthritis, and preferably after 2 weeks [4]. A similar principle is presented in the Portuguese guidelines for the treatment and diagnosis of gout [5]. However, such tactics often lead to unsatisfactory results. Firstly, after the exacerbation subsides, patients trained to independently take anti-inflammatory drugs to relieve subsequent attacks of arthritis often neglect the need for repeated visits to the doctor and urate-lowering therapy will simply not be prescribed; and secondly, having received information about its negative impact on the course of current arthritis, patients in the future tend to discontinue urate-lowering drugs during the occurrence of such attacks or completely avoid taking them [6, 7].
The updated recommendations of the European League Against Rheumatism, mentioning the problem, indicate that there is not yet enough data to make a specific decision on the timing of starting urate-lowering therapy [8]. This is not entirely true. Thus, recent studies allow us to be skeptical about the need to pause when prescribing urate-lowering drugs. In a randomized, double-blind, placebo-controlled, single-center study, TH Taylor et al. 57 patients with an acute attack of gouty arthritis were included, randomized into 2 groups: taking allopurinol at a starting dose of 300 mg/day or placebo. To relieve arthritis, all patients were prescribed indomethacin 50 mg 3 times a day for 10 days, followed by colchicine 0.6 mg 2 times a day for 90 days to prevent attacks.
From the 11th day of observation, all patients from groups 2 also received allopurinol; the study has been open-label since then. When analyzing the average daily pain intensity on a visual analogue scale (VAS) on a 10-point scale in the first 10 days of observation, even minimal differences in the groups were not obtained; moreover, by the end of observation, the average values of pain intensity in the allopurinol group were even slightly less (0 .18 mm in the allopurinol group versus 0.27 mm in the placebo group; p=0.54). A further 3-month follow-up did not record any differences in the frequency of acute attacks recorded in 2 patients taking allopurinol and 3 patients taking placebo (p = 0.6). Thus, the use of allopurinol during an acute attack of gout was not associated with an increase in pain intensity during the current attack, nor with an increase in the frequency of recurrent flares compared with patients who were prescribed allopurinol after relief of arthritis [9]. A similar placebo-controlled study showed that the use of allopurinol during an acute attack did not affect not only the intensity of pain, but also the duration of the current exacerbation [10]. This fact is especially important given the fact that the time spent on relief of arthritis can significantly delay the start of urate-lowering therapy. Interestingly, there were no differences in mean serum sUA levels between the allopurinol and placebo groups at either 14 days (during which the allopurinol dose was 100 mg/day) or 28 days (the allopurinol dose was 200 mg/day). It is likely that slow titration of the drug dose does not lead to sharp fluctuations in serum UA levels, thereby reducing the risk of exacerbations of arthritis.
This opinion about the need to take urate-lowering drugs without waiting for relief of an acute attack of arthritis is supported by the patients themselves, arguing that it is possible to quickly control gout by achieving serum UA levels as quickly as possible [11]. However, if the patient has concerns about the use of drugs during an attack, it is rational to delay the initiation of urate-lowering therapy until the attack resolves.
Use of concomitant prophylactic anti-inflammatory therapy
It is known that taking any drugs that reduce the serum level of sUA, regardless of their mechanism of action (allopurinol, febuxostat, peguricase, benzobromarone) is associated with an increase in the frequency of arthritis attacks in the first months of such therapy [12]. At the same time, the use of symptomatic anti-inflammatory therapy through long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine or glucocorticosteroids (GCS) can reduce the risk of exacerbation during initiation and dose selection of urate-lowering drugs [13, 14]. The main question under discussion is which specific drugs are best to use for this purpose.
The most popular recommendations are from the European League Against Rheumatism, where the choice of a specific drug for the prevention of arthritis attacks is at the discretion of the physician and includes the prescription of low-dose colchicine or NSAIDs (also in the minimally effective anti-inflammatory dose, with gastroprotective therapy if necessary) [8].
A broader list of drugs is proposed in the latest recommendations of the American College of Rheumatology, where, if there are contraindications to the use of NSAIDs and colchicine, it is worth considering the possibility of prescribing low doses of GCS [11].
Contrasting with them are the recommendations of French rheumatologists, who are limited to the use of only low doses of colchicine for the prevention of arthritis attacks [15].
On the one hand, colchicine is indeed the most fully studied in terms of its ability to reduce the likelihood of arthritis attacks when initiating urate-lowering therapy and, even at a high cost, is economically feasible, according to a study by PC Robinson et al. [16].
However, it is not always possible to prescribe the optimal dose of colchicine, especially in patients with chronic kidney disease (CKD); the drug is not always well tolerated given the occurrence of nausea and diarrhea, and when taken together with HMG-CoA reductase inhibitors, fibrates, verapamil, diltiazem, clarithromycion, etc. may increase the risk of developing acute myopathy and aplastic anemia, especially in old age [17–19].
In any case, the choice of a specific drug must be conscious and justified. At the Federal State Budgetary Institution NIIR named after. V.A. Nasonova is conducting a prospective study to compare the effectiveness and safety of various anti-inflammatory drugs used to prevent arthritis attacks. A dynamic examination of 97 patients with gout was carried out over 24 weeks, which included the continuous use of combined urate-lowering and preventive anti-inflammatory therapy.
When initiating urate-lowering therapy, allopurinol 100 mg/day was prescribed, followed by titrating the dose until the target sUA level was achieved, which was defined as <360 µmol/l for all patients or <300 µmol/l for patients with severe tophi gout. A feature of the study was the use of allopurinol and febuxostat in the maximum permissible doses, strictly based on existing national clinical guidelines.
Anti-inflammatory therapy was prescribed according to the algorithm presented in the figure.
Anti-inflammatory therapy was carried out based on the algorithm proposed by the authors, which included the sequential use of colchicine 0.5 mg/day, in case of contraindications and/or poor tolerability - NSAIDs in the minimum effective anti-inflammatory dose, in case of intolerance or the presence of contraindications - GCS (prednisolone 7.5 mg/day).
As a result, only 12% of patients could not receive preventive anti-inflammatory therapy, while among them the likelihood of developing an acute attack of arthritis was 2.5 times higher than among those taking the above drugs (75 vs. 35%, respectively; p = 0.008).
When comparing individual groups of anti-inflammatory drugs, NSAIDs turned out to be significantly more effective than colchicine and corticosteroids in terms of the frequency of arthritis attacks and their duration (p <0.05 in both cases), and the intensity of pain according to VAS after 6 months of observation did not differ significantly between groups (NSAIDs, GCS, colchicine).
There were no significant differences between different groups of anti-inflammatory drugs in the incidence of side effects, which is consistent with the results of similar studies [19, 23].
Choice of urate-lowering therapy
In the Russian Federation (RF), only two drugs are currently registered for the treatment of gout, both are xanthine oxidase inhibitors, but even with such a small choice, the principles for prescribing these two drugs differ in various international and national recommendations.
The first recommendations that discussed the possibility of prescribing febuxostat were the recommendations of the American College of Rheumatology, published in 2012, where the decision on the choice of a specific drug - allopurinol or febuxostat - was supposed to be made individually [24]. In 2021, the randomized, prospective, multicenter CARES (Gout and Cardiovascular Morbidities) trial found higher rates of cardiovascular and all-cause mortality among patients with gout treated with febuxostat compared with allopurinol [25]. However, a number of issues discussed, along with the results of methodological limitations of the study, do not allow a clear conclusion about the benefits of allopurinol [26–28], and several other studies did not find any differences in relation to the cardiovascular safety of the drugs [29, 30]. For example, in a study by J. Foody et al. The frequency of cardiovascular outcomes was analyzed in patients with gout with the presence of cardiovascular diseases and CKD who took allopurinol and febuxostat [31]. Thus, the incidence of adverse cardiovascular outcomes in patients with gout and CKD or cardiovascular diseases, including coronary artery disease, cerebrovascular disease, peripheral vascular disease and CHF, when taking febuxostat was almost 1.5 times less than in patients taking allopurinol , and the differences were significant.
If initially it was planned to limit the use of febuxostat as much as possible, even to the point of banning its use [32], then today the attitude towards the drug has begun to change in the opposite direction. Thus, in accordance with the latest recommendations of the American College of Rheumatology (ACR - American College of Rheumatology), allopurinol should be prescribed to all patients, including patients with moderate to severe CKD (stage ≥3), however, even in the presence of cardiovascular pathology, febuxostat should be prescribed not recommended only “conditionally” [11].
An even wider niche for the use of febuxostat in patients with gout is defined in the recommendations of the French Society of Rheumatology, where its use is justified in the case of a decrease in eGFR <60 ml/min/1.73 m2, provided the patient does not have severe cardiovascular pathology, and with eGFR <30 ml/min/1.73 m2 its administration is a priority over allopurinol [15].
X. Liu et al. A prospective study was conducted that included patients with hyperuricemia and CKD stages 3–5, which assessed the ability to achieve target UA levels and renal function [33]. 112 patients were treated with febuxostat and allopurinol in 96 patients. After 6 months of therapy, the target sUA level was achieved in 96.4% of patients receiving febuxostat and 37.5% receiving allopurinol, while eGFR in the febuxostat group increased from 28.45 to 30.65 ml/min/1.73 m2 and decreased from 28.06 to 24.39 ml/min/1.73 m2 in patients taking allopurinol.
Febuxostat can be used in patients with gout and CKD at doses of 80 and 120 mg/day without the need for their GFR adjustment, and with caution if eGFR is <30 ml/min/1.73 m2. Thus, in a study by SH Kim et al. febuxostat has been shown to have a good safety and efficacy profile in patients with gout in stages 4–5 CKD who are not already on dialysis [34].
In general, taking into account the low cost, sufficient effectiveness and good tolerability of allopurinol, incl. high doses of the drug, there is no doubt about the advisability of its use as a first-line drug of therapy. However, in patients with severe CKD, the use of febuxostat seems to be preferable. A similar approach is supposed to be used in practice, based on domestic recommendations [35].
Use of interleukin-1 (IL-1) inhibitors
On the one hand, the use of IL-1 inhibitors has been considered for almost 10 years as one of the components of the treatment of an acute attack of arthritis, however, the possibility of their actual use is still quite modest, because in many countries they are either not registered or gout is not mentioned as an indication for their use. The ACR and EULAR (European League Against Rheumatism) recommendations suggest the use of IL-1 inhibitors solely for the purpose of relieving an acute attack of arthritis [8,11], however, the domestic version of the clinical recommendations considers the possibility of prescribing them to patients with chronic severe gout and as a method of preventing exacerbations of arthritis [35].
In a study by N. Schlesinger et al. the effectiveness of different doses of canakinumab (25 mg, 50, 100, 200 or 300 mg) and colchicine 0.5 mg/day was compared [36]. At 16 weeks, there was an average 67% reduction in the incidence of arthritis in patients treated with canakinumab ≥50 mg compared with colchicine based on a negative binomial model (rate ratio: 0.28 to 0.38; p≤0.0083) , and the risk of having at least one attack of arthritis was 64–72% lower.
D. Solomon et al. compared the incidence of arthritis attacks when using urate-lowering drugs in patients with different initial serum sUA concentrations (≤404.5 µmol/l, 404.6–535.3 and ≥535.4 µmol/l) [37]. The treatment was canakinumab (50 mg or 150 or 300 mg by subcutaneous injection), which was administered every 3 months, with a follow-up period of almost 4 years. Quarterly administration of canakinumab was associated with a significant reduction in the risk of developing gout attacks, independent of changes in serum sUA levels.
A large post-marketing study was also conducted in our country [38]. Twenty patients with acute arthritis and failure of previous anti-inflammatory therapy were prescribed subcutaneous canakinumab at a dose of 150 mg. Over the next 4 months, the dose of allopurinol was titrated, while the target level of sUA was achieved in 85% of patients, attacks of arthritis were extremely rare, and additional symptomatic therapy was required in only 15% of patients. Moreover, a retrospective analysis after 5 years showed that patients previously treated with canakinumab were more likely to maintain target sUA levels when taking urate-lowering drugs than those who received standard anti-inflammatory therapy (75 vs. 20%, respectively; p = 0.005) [ 39].
Although this group of drugs continues to be considered as a “therapy of desperation” by patients with the most severe course of gout and the presence of contraindications to other symptomatic treatment of the disease, both the presence of high efficacy and preventive effect in relation to cardiovascular outcomes [40] suggests great potential their practical use.
Diet therapy
The role of nutritional therapy in the treatment of gout is being reconsidered. If earlier, for example, in the recommendations of the European League Against Rheumatism, lifestyle and diet were the first point and were presented as a fundamental component of successful treatment of gout [41], but now in the updated recommendations of the ACR or the Interdisciplinary Consensus on the Treatment of Gout and Hyperuricemia of Taiwan, limiting the consumption of those or other products are either recommended “conditionally” [11], or the fact of low effectiveness of diet changes and the priority of drug therapy is simply recognized [42].
In a study by TJ Major et al. Genetic changes have been shown to be much more important in the development of hyperuricemia than the effects of diet, for example, one unit of beer increased serum UA concentrations by only 0.16 mg/dL [43]. Although another study showed that alcohol consumption, even in moderate quantities, increases the risk of developing arthritis attacks after consumption, regardless of the type of alcoholic drink [44].
The use of serum and vitamin C to reduce UA levels is also considered irrational. In a study by LK Stamp et al. it was shown that the use of vitamin C 500 mg/day in patients with gout for 8 weeks did not have a significant urate-lowering effect, despite the fact that the level of ascorbate in the blood plasma increased [45].
Many studies examining changes in serum UA levels depending on a decrease in body mass index (BMI) also did not reveal significant changes [46, 47]. At the same time, it has been shown that an increase in BMI by more than 5% is associated with a higher risk of relapse of acute arthritis by 60%, and a decrease in BMI>5% with a lower one by 40% compared with those whose BMI did not change [ 48]. According to the results of a long-term retrospective analysis of clinical manifestations in patients with gout, isolated dieting without taking urate-lowering drugs did not lead to the achievement of the target serum uric acid level in any of 18 cases, although the average body weight decreased [6].
The ACR recommendations, among other postulates, also formulated conditionally “informal” recommendations, one of which calls for avoiding the formation in patients of a feeling of guilt due to a suboptimal lifestyle and the stigmatization associated with it. It is necessary to be extremely careful when asking a patient about his eating habits: the patient should not feel even the slightest “blame” and condemnation from the doctor. At the same time, it is necessary to convey to the patient that, although diet correction leads to only a minimal decrease in sUA levels, its violation can serve as a risk factor for arthritis attacks [11].
Thus, we can talk about a shift in this vector of treatment for gout: diet therapy can lead to only a slight decrease in the serum level of sUA, its main goal is to reduce the frequency of exacerbations of arthritis.
Conclusion
Thus, according to modern ideas, we can generally formulate several proposed positions in the treatment of gout that differ from the canonical ones.
All patients with an established diagnosis of gout should be prescribed urate-lowering drugs in order to achieve the target level of sUA, which should be initiated without waiting for a 14-day period after the exacerbation has subsided.
Allopurinol should still be considered as first-line urate-lowering therapy, but febuxostat is preferred if the patient has CKD.
Prevention of arthritis attacks should be carried out with the use of colchicine, NSAIDs or corticosteroids, considering the possibility of using each in the specified sequence, and, perhaps, in the case of contraindications and ineffectiveness of these drugs, the use of IL-1 inhibitors should be considered, at least in patients with severe gout.
Diet therapy is solely an auxiliary method that helps reduce the likelihood of exacerbation of arthritis, but should not be considered as an effective means of combating hyperuricemia.
Conflict of interest. The work was carried out as part of the applied scientific research “Technology for the use of various anti-inflammatory drugs for the prevention of arthritis attacks when prescribing urate-lowering therapy in patients with gout” (No. 2020-397-007). The authors did not receive any royalties for the article. M.S. Eliseev confirms that he receives fees for lecturing.
Arterial hypertension in patients with gout: treatment options
Currently, gout is considered an important general medical problem, which is associated not only with the increasing prevalence of the disease, but also with the data obtained on the effect of hyperuricemia on the progression of atherosclerotic vascular lesions [1, 2]. According to experts, gout is a metabolic disease [3, 4], and hyperuricemia is one of the most important components of the metabolic syndrome. Back in the 60s of the last century, a close relationship was discovered between disorders of purine metabolism and hypertriglyceridemia [6]. According to the results of an 8-year study, a connection between hyperuricemia and insulin resistance was proven [5]. Hyperuricemia is an independent risk factor for cardiovascular diseases [1, 2, 7], so the diagnosis and treatment of gout, hyperuricemia, as well as complications of the disease are an urgent problem in therapy.
In addition to the direct pathological effect of elevated levels of uric acid on the vascular wall, the effect of elevated blood pressure (BP), which is extremely common in this category of patients, becomes important in patients with gout [8]. Arterial hypertension (AH), in turn, significantly increases the risk of cardiovascular accidents [8, 9]. An urgent problem is the use of pathogenetically based, safe antihypertensive therapy that ensures adequate blood pressure control throughout the day. In gout patients suffering from hypertension, it is necessary to take into account the interaction of complex metabolic processes so as not to increase the risk of therapeutically induced gout [3]. The metabolic safety of drugs used to treat hypertension in patients with gout is of paramount importance. The metabolic neutrality of drugs is understood as their effect not only on lipid and carbohydrate metabolism, but also on the level of uric acid [3]. In addition, adequate antihypertensive therapy implies the choice of a drug that has the ability to further reduce the risk of cardiovascular complications and reduce the severity of endothelial dysfunction. Not all drugs included in the standard treatment of cardiovascular diseases satisfy these conditions in patients suffering from gout. Thus, diuretics are considered first-line drugs for long-term therapy of patients with hypertension. All classes of diuretics are contraindicated in gout. It has been shown that there is no safe class of diuretics. All drugs in this group inhibit the excretion of uric acid, leading to hyperuricemia; β-blockers are also not the drugs of choice for the combination of gout and hypertension, as they increase insulin resistance and hyperinsulinemia, exacerbating hyperuricemia [4].
It is currently known that metabolically neutral drugs that provide optimal blood pressure control are long-acting dihydropyridine calcium antagonists (amlodipine), angiotensin-converting enzyme inhibitors [4], and an angiotensin II AT1 receptor blocker (losartan) [10]. Among these groups of drugs, a special place belongs to calcium antagonists. The mechanism of action is associated with blocking slow calcium channels and preventing intracellular hypercalcemia, relaxing smooth muscles and reducing peripheral vascular resistance. The half-life of amlodipine is 35–50 hours. Numerous multicenter studies (NORDIL, INSIGHT, VHAT, HOT, ALLHAT) have shown a reduction in the risk of cardiovascular complications during therapy with long-acting calcium antagonists. An undeniable advantage of the drugs is the possibility of using them in patients with metabolic syndrome, since they do not have a negative effect on carbohydrate, lipid, and purine metabolism [11, 12].
Despite the large number of studies devoted to diagnosis and the tactics of choosing drugs for hypertension, until now there is not enough data on the characteristics of the daily blood pressure profile in patients with gout, the effect of long-acting calcium antagonists in the combination of gout and hypertension.
The purpose of our study was to study the circadian rhythms of blood pressure and the effectiveness of amlodipine in the combination of gout and hypertension.
Material and methods
The study included 40 patients with primary gout - the main group (MG) (32 men and 8 women), average age 52.88 ± 2.08 years (from 30 to 76 years). The diagnosis of gout was determined based on the classification criteria proposed by Wallace et al, recommended by the ARA in 2001. Non-inclusion criteria were the presence of conditions associated with hypertension (including diabetes mellitus, coronary heart disease), concomitant chronic diseases in the acute stage, an acute attack of gout arthritis. All examined patients suffered from hypertension (disease duration from 1 to 30 years), the risk was assessed as high and very high.
The comparison group (CG) consisted of 20 patients with arterial hypertension, comparable in age, gender, and comorbidities. The control group (CG) included 20 clinically healthy individuals. All examined individuals underwent a general clinical examination, 24-hour blood pressure monitoring in a hospital setting, and determination of the antithrombogenic activity of the vascular wall.
In patients with gout, studies were carried out necessary to confirm the diagnosis, identify the characteristics of the course of the disease, damage to various organs and systems (uric acid in blood serum and 24-hour urine, radiography of the affected joints, puncture of the joints, ultrasound examination of the kidneys). The joints of the lower extremities were most often affected. In the vast majority of patients (87%), joint involvement began with arthritis of the metatarsophalangeal joint of the first toe. The average duration of the disease was 9.65 ± 2.03 years (from 0.6 to 32 years), they consulted a doctor on average after 10 years of illness. 68% of patients were diagnosed with tophi gout, which included subcutaneous and intraosseous tophi (the “puncture” symptom), and nephrolithiasis. Hyperuricemia was detected in 73% of patients with gout. Arterial hypertension in this category of patients was clinically characterized by low symptoms, and therefore more than half of the patients did not control blood pressure and did not regularly take antihypertensive drugs. At the outpatient stage, 46% of the examined patients with gout for antihypertensive purposes took ACE inhibitors, calcium antagonists, adrenoblockers, diuretics (10%), combination drugs; during therapy, the target blood pressure level was achieved in only 15% of patients.
Upon admission to the hospital, all examined individuals underwent 24-hour blood pressure monitoring with a frequency of 15 minutes during the daytime and 30 minutes at night. The following indicators were assessed: average blood pressure, maximum, minimum blood pressure, blood pressure variability, hypertensive blood pressure time index. All parameters were determined for both systolic blood pressure (SBP) and diastolic blood pressure (DBP).
All patients were prescribed amlodipine (Amlovas) as antihypertensive therapy at an initial dose of 5 mg/day. The dose of the drug was titrated after 3–5 days of hospital stay, increasing to 10 mg/day if necessary or combining with an ACE inhibitor. After 3 months of regular use of antihypertensive drugs, repeated 24-hour blood pressure monitoring was performed. During this time, monitoring of the effectiveness of therapy and the presence of side effects was carried out during monthly patient visits.
Statistical analysis was carried out using the STATISTICA 6.0 application package, descriptive statistics. The results were regarded as statistically significant when the achieved significance level (p) was less than 0.05.
results
Average data on daily blood pressure monitoring in patients with gout and patients suffering from hypertension are presented in Table.
In patients with gout, higher values of average systolic, diastolic, pulse blood pressure, maximum and minimum blood pressure, hypertension time index, and blood pressure variability were noted, although these differences compared with similar parameters in the comparison group did not reach statistical significance.
However, there were significant differences in the degree of blood pressure reduction at night. Thus, in the majority of patients with gout (73.7%), a daily profile with an insufficient degree of blood pressure reduction (Non-dipper) was revealed; in 21% of patients, a stable increase in blood pressure was recorded at night (Night-peaker); only 5 patients had a normal degree of blood pressure reduction. % of patients (Dipper). While in patients with hypertension, the Dipper profile was predominantly observed (62.5%), in 25% of cases - Non-dipper, in 12.5% of patients - Night-peaker. Thus, among patients with gout, the Non-dipper profile was significantly more often recorded compared to those suffering from hypertension (p < 0.01).
When analyzing the effectiveness of therapy with amlodipine (Amlovas) for hypertension in patients with gout, it should be noted that all patients indicated a fairly high effectiveness of the drug according to subjective sensations and casual measurements of blood pressure. The only patient discontinued the drug on his own due to the sensation of “palpitations” 2 days after taking amlodipine. There were no other possible side effects in the observed group of patients. In 18 (45%) patients, the target blood pressure level was achieved within 4–6 days on the background of monotherapy - taking 5 mg of the drug per day.
In the remaining 22 (55%) patients, the target blood pressure level was not achieved 4–6 days after starting amlodipine (Amlovas), which required increasing the dose to 10 mg/day. After 3–4 days from the moment of increasing the dose of the drug, while monitoring the effectiveness of the therapy, normalization of blood pressure was noted in 19 (47.5%) patients, i.e., blood pressure stabilized after 7–10 days from the start of taking the drug. In 7.5% (3) of patients, it was not possible to achieve target blood pressure values within 7–10 days, and therefore combination antihypertensive therapy (amlodipine and ACE inhibitor enalapril) was recommended.
Subsequently, after discharge from the hospital, blood pressure was measured at monthly visits. While taking recommended antihypertensive therapy, 29 (73%) patients had blood pressure within the target range, and 10 (25%) patients had blood pressure within the range of high normal blood pressure. All patients noted good tolerability of the drug Amlovas.
After 3 months of therapy, according to the results of 24-hour blood pressure monitoring, the indicators of average SBP and DBP, pulse blood pressure significantly decreased, and the hypertension time index decreased. However, there were no statistically significant differences in changes in the daily blood pressure profile, which may be due to insufficiently long-term use of amlodipine.
conclusions
Patients with gout who suffer from arterial hypertension due to low-symptoms of high blood pressure, high social activity, and the presence of articular syndrome are characterized by low adherence to antihypertensive therapy.
Patients with gout have disturbances in the circadian rhythm of blood pressure, which in most cases manifests itself in an insufficient degree of blood pressure reduction at night. Violation of the 24-hour blood pressure profile is an additional risk factor for cardiovascular complications [13].
Thus, in patients with gout suffering from hypertension, compared to patients with essential hypertension, there are additional risk factors for cardiovascular events in the form of disturbances in the daily blood pressure profile. Considering the low symptoms, low adherence to antihypertensive therapy, effectiveness, good tolerability, metabolic neutrality, and safety of use, the drugs of choice in patients with hypertension in combination with gout are long-acting calcium antagonists (amlodipine).
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A. P. Rebrov , Doctor of Medical Sciences, Professor N. A. Magdeeva SSMU , Saratov