Felodipine 2.5mg modified-release / Ramipril 2.5mg tablets

In the sentence beginning ‘Explicit recommendations regarding alternative options…’ in the Abstract section of this article, the term ‘for three prescribing cascades’ should have read ‘for five prescribing cascades.’ The complete sentence should read: ‘Explicit recommendations regarding alternative options were given for five prescribing cascades.’ In the sentence beginning ‘For 22 prescribing cascades, …’ the text ‘but only for three it was mentioned to which medication (Table 2)’ should have read ‘but only for five it was mentioned to which medication (Table 2).’ The complete sentence should read: ‘For 22 prescribing cascades, recommendations were made to switch the index medication but only for five it was mentioned to which medication (Table 2).’ The following sentence, which previously read: ‘Kirwan et al. [72] recommended the switch to betaxolol when an obstructive airways disorder is experienced when using antiglaucoma preparations, whereas Avorn et al. [71] recommended to switch to any other antiglaucoma preparation.’ should read ‘Avorn et al [71] recommended to switch to beta-1-selective agents when an obstructive airways disorder is experienced when using nonselective beta-blockers for glaucoma.’ In Table 2, ‘Prescribing cascade’ section, ‘Cardiovascular system’ subsections, ‘ACE-inhibitors, including combinations (C09A, C09B)’ and ‘ACE-inhibitors (C09AA)’ row: The cell entry in column 6, which previously read: “DL [26]” and “DL [28]” should be deleted. In the same subsection, ‘Atorvastatin’ row: The cell entry in column 6, which previously read: ‘SW [31]’ should read ‘SW (fluvastatin, lovastatin, pravastatin, rosuvastatin) [31].’ In the ‘Dihydropyridines (C08CA)’ row of the same subsection: The cell entry in column 6, which was previously empty should read ‘DIS, DL, SW [39].’ In the ‘Amlodipine, nifedipine, felodipine**’ row: The cell entry in column 6, which was previously empty should read ‘DL, DIS [41].’ Under the ‘Musculo-skeletal system (M)’ subsection, ‘Miscellaneous NSAIDs (within M01A)’ row: The cell entry in column 6, which previously read: ‘DIS, DL, SW [52]’ should read ‘DIS, DL, SW (acetaminophen) [52]’. In the ‘Sensory organs (S)’ subsection, ‘Antiglaucoma preparations and miotics (S01E)’ row: The cell entry in column 6, which previously read: ‘SW (betaxolol) [71, 72]’ should read ‘SW (beta-1-selective agents) [71].’ And the cell entries in column 6, which previously read: ‘SW [71, 72]’ and ‘DIS [73]’ should be deleted. The incorrect and correct versions of Table 2 are given below. Incorrect version of Table 2: Table 2 Prescribing cascades with at least one positive significant association between the index and marker medication, with confirmed ADRs and a dose-dependency analysis and/or recommendations to prevent or reverse the prescribing cascade Prescribing cascade analyses^a Dose-dependency analysis^b O = Other^c O = Other^c 1. Metoclopramide (A03FA01) Extrapyramidal syndrome (10015836) Anti-parkinson drugs (N04) +R [21, 22] +R [21] SW (ondansetron or granisetron) [21] 2.

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BACKGROUND: Currently, most studies primarily focus on directly comparing the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs), the two major classes of antihypertensive drugs. Moreover, the majority of studies are based on randomized controlled trials and traditional meta-analyses, with few exploring the efficacy and safety comparisons among various members of ACEIs and CCBs. METHODS: ACEIs and CCB were searched for in randomized controlled trials in CNKI, Wanfang, VIP, China Biology Medicine Disc (Si-noMed), PubMed, EMbase, and Cochrane Library databases. The search can be conducted till November 2022. Stata software (version 16.0) and R 4.1.3 was used for statistical analysis and graphics plotting, applying mvmeta, gemtc, and its packages. Meta-regression analysis was used to explore the inconsistencies of the studies. RESULTS: In 73 trials involving 33 different drugs, a total of 9176 hypertensive patients were included in the analysis, with 4623 in the intervention group and 4553 in the control group. The results of the analysis showed that, according to the SUCRA ranking, felodipine (MD = -12.34, 95% CI: -17.8 to -6.82) was the drug most likely to be the best intervention for systolic blood pressure, while nitrendipine (MD = -8.01, 95% CI: -11.71 to -4.18) was the drug most likely to be the best intervention for diastolic blood pressure. Regarding adverse drug reactions, nifedipine (OR = 0.32, 95% CI: 0.14-0.74) was the drug most likely to be the safest. CONCLUSION: The research findings indicate that nifedipine is the optimal intervention for reducing systolic blood pressure in hypertensive patients, nitrendipine is the optimal intervention for reducing diastolic blood pressure in hypertensive patients, and felodipine is the optimal intervention for safety.

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BACKGROUND: Female sexual dysfunction (FSD) among females with hypertension (HTN) is frequently overlooked, with a reported prevalence of 42.1%. OBJECTIVES: We aimed to determine the impact of beta-blockers (BBs), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), and thiazides on sexual function in hypertensive females. METHODS: A prospective randomized controlled trial enrolled 125 female participants. Group (1) included 25 normotensive females serving as the controls. Groups (2) and (3) consisted of 50 controlled and uncontrolled hypertensive patients who received BBs, respectively. Groups (4) and (5) consisted of 50 patients with controlled and uncontrolled HTN who received ACIs/ARBs, respectively. Each group consisted of patients who received one tablet daily of ramipril 2.5 mg for one month, while the other half received one tablet daily of valsartan (VAL) 80 mg for the same duration. After one month, the subjects were transitioned to a daily regimen of one tablet of ramipril 2.5 mg combined with hydrochlorothiazide 12.5 mg, as well as one tablet of VAL 80 mg with hydrochlorothiazide 12.5 mg for two months, respectively. RESULTS: Controlled and uncontrolled hypertensive patients receiving ACEIs/ARBs, as well as controlled hypertensive patients receiving BBs, demonstrated a significant decrease in serum total testosterone and free testosterone levels, accompanied by a significant increase in estradiol after 3 months. Furthermore, controlled and uncontrolled hypertensive patients receiving ACEI/ARBs showed significant increases in all female sexual function (FSF) domains and total FSF scores after 3 months. Consistently, controlled hypertensive patients receiving BBs showed significant improvements across all domains of the validated Arabic version of the female sexual function index (ArFSFI) and the total score, comparable to the ACEI/ARB groups, except for pain. Conversely, uncontrolled hypertensive patients receiving BBs demonstrated significant increases in scores for desire and arousal and orgasm and satisfaction after 3 months. After three months, there was a significant reduction in the GAD-7 scores among all hypertensive patients. CONCLUSION: ACEIs/ARBs demonstrated a favorable effect on FSF. Future large-scale cohort studies are warranted to validate these findings as this study was a single center and of small sample size.

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For many years, pharmaceutical expenditure has been the second largest cost item for statutory health insurance funds (SHI) in Germany after hospital costs. Since prescriptions and expenditure on medicines play such a major role in the German healthcare system, the question arises as to what causes changes in prescriptions. To answer this question, the prescribing trends for the top 10 drugs in 2022 were analyzed over a period of 38 years, from 1985 to 2022. The prescribed defined daily doses (DDD) and the costs per defined daily dose for the 10 medicines were taken from the Arzneiverordnungsreport (AVR) from 1986 to 2023, and the changes in prescribing behavior and their causes were analyzed. The ten most important medicines in 2022, accounting for over 41% of all prescribed daily doses, were ramipril, candesartan, pantoprazole, amlodipine, atorvastatin, levothyroxine, torasemide, simvastatin, bisoprolol, and metoprolol. There are many different reasons for an increase in prescriptions, such as the introduction of generics, a positive study, or a price reduction. Further reasons for an increase in prescriptions are an extension of the indication or the recall of a competing medicine. A change in guidelines or the increasing treatment of laboratory values without clinical symptoms can also lead to an increase in prescriptions. There are also many different reasons for a drop in prescriptions, such as the generic launch of a competitor medicine or a positive study for a competitor medicine. Other reasons for a drop in prescriptions are a negative study or a discussion about the use of a drug. Sometimes, the reasons for prescription changes are also irrational. Overall, this is the most comprehensive long-term analysis of drug prescriptions in Germany. Our data is helpful for predicting drug prescriptions and for preventing future drug shortages not only in Germany but also worldwide.

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High blood pressure (BP) is the greatest single reversible cause of death and disability worldwide [1,2]. Historically, a problem of higher income countries, over the last four decades, lower and middle-income countries have witnessed the largest increase in hypertension prevalence [1]. The scientific evidence is undisputed – pharmacological lowering of BP significantly reduces cardiovascular events by 20–60% [3,4]. However, despite the global availability of cheap, well tolerated and effective antihypertensive medications, half of those with hypertension remain unaware of their condition, and, of those who are aware, only half receive effective treatment [5]. Whilst there are variations in the identification, treatment and control of high BP across the world, what is striking is that in every region, a large proportion of people with raised BP do not reach targets [5]. The stark question is why is there not a public outcry for the failure to identify, treat and control hypertension – the consequences of which are placing a huge burden on global health services, global economy and, most importantly, people living with hypertension? Society seems happy to allow the food industry conglomerates (‘Big Food’) to fuel the BP and obesity epidemics via their relentless marketing of highly processed foods that are invariably high in both dietary salt and sugar. The low cost of such ‘foods’ also contributes to health inequities and hampers successful management of hypertension by healthcare providers. The association between salt and BP is undisputed [6]. Although the WHO advises adults consume less than 5 g salt/day, global data estimates the average daily salt intake for adults is greater than 10 g, the majority of which comes from processed foods [7]. Devolving responsibility for dietary salt reduction to the individual, who has no control over the ingredients in processed foods (note the salt content of some breakfast cereals is higher than seawater!) is absurd [8]. We strongly support the view of the WHO and Action on Salt, that we must take a radical and systematic approach to reduce the salt content in processed food via co-ordinated government policies. The obesity pandemic is not only fuelling the rise in diabetes but also hypertension [9,10]. This is particularly apparent in lower and middle-income countries where a ‘western diet’ promoted by ‘Big Food’ is responsible for the weight gain of the population and the increasing prevalence of obesity [1]. Weight reduction is an effective method of BP lowering but is difficult to achieve and maintain [11]. This is unsurprising given the biological basis to obesity and the ready availability of cheap, highly addictive, high-fat, high-sugar and high-salt processed foods [12]. Clinical trials are currently in progress to evaluate the use of GLP-1 and SGLT2 inhibitors as adjuncts to antihypertensive therapy – but we question the ethics of relying on pharmaceuticals to counteract a problem largely driven by the food industry. In a misguided attempt to address these issues, National and International Hypertension Societies have produced countless guidelines on hypertension and its management [13–16]. Guidelines started as a practical tool to support clinicians implement evidence-based medicine by providing clear rationales for treatment advice with a focus on implementation [17]. Unfortunately, guideline development has evolved into a complex industry with convoluted systems of evidence grading and text of such verbosity that the result is both hard to read and implement [18,19]. In our view, current guidelines do more for the H-index of the authors than improving the management of people living with high BP. We propose going back to basics and creating a guideline that supports clinicians improve outcomes for the vast majority of people living with high BP – and to kick start this process we offer the ‘4 S’ approach for successful blood pressure control (Fig. 1).FIGURE 1: The ‘4 S’ approach for successful blood pressure control. ABPM, ambulatory blood pressure monitoring; BIHS, British and Irish Hypertension Society; FBC, full blood count; HBPM, home blood pressure measurement; NICE, National Institute for Health and Care Excellence; TSH, thyroid-stimulating hormone; U&Es, urea and electrolytes.Salt and satiety: we recommend educating people about the hidden salt content of highly processed and preprepared foods such as bread, breakfast cereals, ‘ready meals’ and swapping domestic table salt for high potassium alternatives [20]. We recommend supporting individuals to maintain a healthy weight by diet and appropriate exercise, acknowledging the biological basis to obesity and offering appropriate pharmacological and nonpharmacological therapies. Sensible drugs, sensible doses: we recommend the British and Irish Hypertension Society (BIHS-endorsed) four-step National Institute for Health and Care Excellence (NICE) hypertension treatment algorithm to achieve BP targets less than 130/80 mmHg in most people [21,22]. Step 1 – initiate therapy with an ACE inhibitor/angiotensin II receptor blocker (A) or calcium channel blocker (C) – based on age and ethnicity. Step 2 – progress to combination therapy (A + C). Step 3 – add a thiazide-like diuretic (A + C + D) Step 4 – if BP remains above target, add a fourth-line agent [21,22]. At each step, drugs and doses should be titrated every 4–6 weeks, wherever appropriate, to ensure BP targets are achieved within 6 months to minimize end-organ damage. We advise therapeutic agents are selected based on clinical efficacy supported by outcome trials demonstrating a reduction in major adverse cardiovascular events, long duration of action and a simple dosing schedule [23,24]. Single-pill combinations have been shown to improve adherence and should be used wherever available [25]. We recommend the following once-daily drugs: 1. A = Lisinopril 10–20 mg or Perindopril 4–8 mg 2. C = Amlodipine 2.5–10 mg 3. D = Chlorthalidone 25 mg or Indapamide SR 1.5 mg 4. Fourth line agent = Spironolactone 12.5–50 mg or Amiloride 10 mg [26–28] 5. Alternative fourth line options = Bisoprolol 2.5–5 mg, Doxazosin XL 4–8 mg, Increase Chlorthalidone to 50 mg We strongly advise avoiding ramipril, felodipine, bendrofluazide, as these either lack outcome data on preventing cardiovascular events and/or are shorter acting than the alternatives in the same therapeutic class. pSeudo resistant hypertension: where BP remains above target, we recommend the following strategy: 1. Re-evaluate for white-coat hypertension, using ambulatory BP monitoring (ABPM) or repeat home blood pressure measurement (HBPM) 2. Objectively assess adherence using Direct Observed Therapy (DOT) and/or urine drug screen 3. Review concurrent medications, over-the-counter remedies and substances of abuse A study by Hayes et al. demonstrated that among 235 patients with apparent resistant hypertension, 25% were partially or totally noncompliant (evaluated by urinalysis) and 25% had normal ABPM [29]. Nonadherence rates are consistent with observations from specialist hypertension clinics in Leicester [30] and Cambridge [31] that also indicate the number of prescribed antihypertensive medications is a strong predictor of adherence. Secondary hypertension: the prevalence of secondary hypertension in the adult hypertensive population is relatively low, with the notable exceptions being individuals with renal disease (50–90%) and hypertension in pregnancy (10%). Of the other secondary causes, hyperaldosteronism is probably the commonest – with an estimated prevalence of between 2 and 10% depending on the definitions used and clinical setting [32]. We recommend a basic blood test including urea and electrolytes (U&Es), creatinine, calcium, phosphate, thyroid-stimulating hormone (TSH), full blood count (FBC) plus urine analysis and renal imaging. Wherever available, we also recommend checking plasma renin and aldosterone. These simple tests are sufficient to exclude most secondary causes of hypertension. For individuals in whom BP remains above target, despite taking at least three antihypertensive medications at maximum tolerated doses, with confirmed adherence and management of concurrent risk factors including dietary salt and weight management, referral to a hypertension specialist may be appropriate for further investigation [22]. ACKNOWLEDGEMENTS Conflicts of interest I.B.W. has received research grants from AstraZeneca, GSK and scientific advisory board consultation fees for Viatris, Astra Zeneca and Roche. S.P. has no conflicts of interest to declare for this manuscript. P.S. has received renumeration for scientific advisory boards and lectures from Viatris.

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