Jan Václavík

Addition of Spironolactone in Patients With Resistant Arterial Hypertension (ASPIRANT) A Randomized, Double-Blind, Placebo-Controlled Trial

There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP >140 mm Hg or diastolic BP >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (n=59) or a placebo (n=58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was −5.4 mm Hg (95%CI −10.0; −0.8) for systolic BP (P=0.024) and −1.0 mm Hg (95% CI −4.0; 2.0) for diastolic BP (P=0.358). The APBM nighttime systolic, 24-hour ABPM systolic, and office systolic BP values were significantly decreased by spironolactone (difference of −8.6, −9.8, and −6.5 mm Hg; P=0.011, 0.004, and 0.011), whereas the fall of the respective diastolic BP values was not significant (−3.0, −1.0, and −2.5 mm Hg; P=0.079, 0.405, and 0.079). The adverse events in both groups were comparable. In conclusion, spironolactone is an effective drug for lowering systolic BP in patients with resistant arterial hypertension.

Randomized Comparison of Renal Denervation Versus Intensified Pharmacotherapy Including Spironolactone in True-Resistant Hypertension Six-Month Results From the Prague-15 Study

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (−8.6 [95% cofidence interval: −11.8, −5.3] mm Hg; P<0.001 in renal denervation versus −8.1 [95% cofidence interval: −12.7, −3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (−12.4 [95% cofidence interval: −17.0, −7.8] mm Hg; P<0.001 in renal denervation versus −14.3 [95% cofidence interval: −19.7, −8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy.

Long-term survival following acute heart failure: The Acute Heart Failure Database Main registry (AHEAD Main)

BACKGROUND The in-hospital mortality of patients with acute heart failure (AHF) is reported to be 12.7% and mortality on day 30 after admission 17.2%. Less information is known about the long-term prognosis of those patients discharged after hospitalization. As such, the aim of this study was to investigate long-term survival in a cohort of patients who had been hospitalized for AHF and then discharged. METHODS The AHEAD Main registry includes 4153 patients hospitalized for AHF in 7 different medical centers, each with its own cathlab, in the Czech Republic. Patient survival rates were evaluated in 3438 patients who had survived to day 30 after admission, and were used as a measurement of long-term survival. RESULTS The most common etiologies were acute coronary syndrome (32.3%) and chronic ischemic heart disease (20.1%). The survival rate after day 30 following admission was 79.7% after 1 year and 64.5% after 3 years. No statistically significant difference in syndromes was found in survival after day 30. Independent predictors of a worse prognosis were defined as follows: age>70 years, comorbidities, severe left ventricular systolic dysfunction, valvular disease or ACS as an etiology of AHF. A better prognosis was defined for de-novo AHF patients, and those who were taking ACE inhibitors at the time of discharge. In a sub-analysis, high levels of natriuretic peptides were the most powerful predictors of high-risk, long-term mortality. CONCLUSION The AHEAD Main registry provides up-to-date information on the long-term prognosis of patients hospitalized with AHF. The 3-year survival of patients following day 30 of admission was 64.5%. Higher age, LV dysfunction, comorbidities and high levels of natriuretic peptides were the most powerful predictors of worse prognosis in long-term survival.

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study.

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT).

AbstractThis study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension.Patients with office systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial. One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned to receive 25 mg of spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization. This study was registered with ClinicalTrials.gov, number NCT00524615.Analyses were done with 150 patients who finished the follow-up (74 in the spironolactone and 76 in the placebo group). At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of −9.8, −13.0, −10.5, and −9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office. The respective DBP differences were −3.2, −6.4, −3.5, and −3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003). Adverse events in both groups were comparable. The office SBP goal <140 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001).Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control.

Antiplatelet therapy in the perioperative period

The current practice of withdrawing aspirin 7-10 days preoperatively may be dangerous in certain groups of patients. The risk of cardiovascular events increases 3-fold after aspirin withdrawal. The average time between aspirin withdrawal and the manifestation of acute coronary syndrome is 8 to 11 days. The withdrawal of clopidogrel earlier than 4-6 weeks after bare metal stent implantation or less than 12 months after drug-eluting stent implantation is very risky and poses a high risk of stent thrombosis and high perioperative mortality. Continuing aspirin perioperatively leads to a 1.5-fold increase in perioperative bleeding complications but it does not lead to a higher severity of bleeding complications or higher mortality. The article analyzes current European and American guidelines for perioperative antiplatelet treatment and suggests an algorithm based on the guidelines to help make clinical decisions.

AHEAD score--Long-term risk classification in acute heart failure.

BACKGROUND The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 μmol/l), D--diabetes mellitus) scoring system. METHODS AHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315). RESULTS Main outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001). CONCLUSION The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.

Positive Influence of Being Overweight/Obese on Long Term Survival in Patients Hospitalised Due to Acute Heart Failure

Background Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the “obesity paradox” on a large cohort with long-term follow-up are lacking. Methods Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5–25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. Results In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26–1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09–1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11–1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. Conclusion These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Unilateral Catheter-based Renal Sympathetic Denervation in Resistant Arterial Hypertension Shows No Blood Pressure-lowering Effect

A 68-year-old woman with resistant essential arterial hypertension despite the regular use of four antihypertensive drugs was referred to the catheter-based renal sympathetic denervation. Due to the complicated anatomy, insertion of the guiding catheter into the left renal artery was not stable. Thus, renal denervation of only the right renal artery was performed. Before and after renal denervation, the patient’s blood pressure was monitored by home blood pressure (BP) telemonitoring. The average 7-day home BP telemonitoring values before and 1, 2, and 3 months after denervation were 187.1/124.1, 193.3/123.1, 198.3/129.6, and 195.2/128.0 mm Hg. After unilateral renal denervation, no BP decrease occurred. This unique case suggests that unilateral catheter-based renal sympathetic denervation in resistant arterial hypertension shows no BP-lowering effect. Therefore, when treating resistant hypertension by catheter-based renal denervation, it seems advisable to try always to perform an effective bilateral procedure.

Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized Prague-15 study

Objectives: The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. Methods: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients. Results: Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001). Conclusion: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.