Systolic hypertension in older patients: are calcium channel antagonists safe?

The Editor and Associate Editors are pleased that our readership will have the opportunity to benefit from a series of contributions by Dr John Rutherford addressing current issues in pharmacology and therapeutics pertinent to coronary artery disease. We are pleased also that Dr Rutherford will provide authoritative perspectives on topics of immediate interest on a regular basis.     

Are angiotensin converting enzyme inhibitors beneficial in patients with aortic stenosis?

Angiotensin converting enzyme (ACE) inhibitors may become an accepted form of treatment for aortic stenosis in the future.     

The calcium channel blocker controversy in patients with diabetic nephropathy: Is there an issue?

Chronic renal failure, proteinuria, and arterial hypertension run in parallel in the presence of diabetic nephropathy. New goal blood pressure levels have been established in diabetic patients: 130/85 mm Hg and 125/75 mm Hg depending on the level of proteinuria being below or above 1 g/d. New and lower threshold blood pressure (> 130/85 mm Hg) to initiate pharmacologic therapy is required in the presence of diabetes mellitus in order to facilitate the strict blood pressure control that is required. It must be considered that both renal and cardiovascular protection are obtained with strict blood pressure control, which otherwise seems to require blockade of angiotensin II effects when proteinuria above 1 g/d is present. While awaiting the publication of long-term follow-up studies looking at renal and cardiovascular outcome in diabetic and other nephropathies in which calcium channel blockers are compared with other antihypertensive drugs, calcium channel blockers will remain the drugs needed to attain the expected goal blood pressure in diabetics, both alone (in the absence of microalbuminuria or macroalbuminuria) or in combination, particularly with angiotensin converting enzyme inhibitors.     

Should cisapride be avoided in patients with diabetic gastroparesis?

The gastrointestinal motility stimulants, cisapride and erythromycin, have been used in the management of diabetic gastroparesis. However, drug interactions may result in prolongation of the electrocardiographic QT interval with the risk of ventricular arrhythmias. These drugs should, therefore, not be used in combination. We report two cases that illustrate inappropriate use of these agents. Moreover, patients with recurrent severe hypoglycemia or renal impairment may be at increased risk from cisapride-related cardiotoxicity. Thus, even as monotherapy, cisapride may pose dangers for high-risk diabetic patients.     

Is calcium supplementation always needed in patients with hypoparathyroidism?

Oral calcium salts are recommended for the treatment of chronic hypoparathyroidism (HypoPT), although dosimetry is variable between individual patients and clinicians. However, patient feedback on calcium salts can be negative, particularly due to gastrointestinal side effects and hypercalciuria‐related complications. We begin with a clinical case of a HypoPT patient taking oral calcium salts following thyroid surgery, who requested support in reducing her dose of these with a view to stopping entirely. To evaluate her request, we first describe the usual treatment of HypoPT according to current guidance and then present data from (a) a case note review of a cohort of 24 HypoPT patients managed with a “no calcium” treatment regimen by single physician (b) a comprehensive online survey of HypoPT patients’ treatment and experiences (n = 330). The case note review found that target range serum calcium levels were successfully achieved in all 24 patients since transitioning to a “no calcium” regimen, without any breakthrough hypocalcaemia‐related symptoms, the development of new renal stones, the occurrence of calcium‐related hospital admissions or the finding of significant hypercalciuria. The online survey identified 36% of HypoPT patients who continued to take activated vitamin D, but had discontinued calcium supplements. HypoPT patients not currently taking calcium reported a significantly lower prevalence of adverse effects and outcomes, both compared with their previous experiences whilst taking calcium and also compared with the 64% of patients who continued to take oral calcium. We conclude that, subject to methodological limitations, there are significant issues of tolerability arising from conventional calcium‐based treatment regimens for patients with chronic HypoPT. For selected patients, it may be reasonable to facilitate a managed therapeutic transition to “no calcium” regimen, and we also propose that calcium‐based regimes be prospectively evaluated against calcium‐free (or calcium‐low) alternatives.     

Endothelin-receptor antagonists in arterial hypertension: Further indications?

Endothelin-1 exerts vasoactive, pro-inflammatory, hypertrophic, and profibrotic properties on the heart, kidney, and blood vessels. Hence, endothelin-receptor antagonists hold the potential to reduce blood pressure and to prevent complications of hypertension, atherosclerosis, and diabetes through blood pressure-independent effects on cardiovascular growth, inflammation, and fibrosis. These potentially important effects of endothelin antagonism may contribute to its therapeutic potential in hypertension and other cardiovascular disorders, including chronic renal failure and diabetes. First clinical trial evidence demonstrates a moderate reduction in blood pressure in studies of patients with mild-to-moderate essential hypertension and patients with resistant hypertension. Future large-scale randomized clinical trials will provide more insight into whether the blood-pressure reduction and promising pleiotropic effects observed with several members of this novel class of drugs, which are already established therapy in pulmonary hypertension, will translate into clinical benefit in patients with arterial hypertension.     

Is scuba diving allowed in diabetic patients treated with insulin?

Scuba diving is usually prohibited in diabetic patients at risk of hypoglycemic attacks (i.e. IDDM and NIDDM treated with sulfonylureas) due to the particular severity of these episodes in a hostile environment. In fact, diabetic subjects can perform this popular leisure activity without extra-risk, provided strict requisites in aptitude, practice and environment are enforced. These limitations lead to the establishment of practical guidelines, as proposed in this paper.     

Do patients with de novo hypertension differ from patients with previously known hypertension when malignant phase hypertension occurs?

Malignant phase hypertension (MHT) represents the most severe form of hypertension, and many consider that this condition only occurs in poorly managed patients with previously known hypertension. To investigate this further, we studied 350 patients with MHT on the West Birmingham MHT database: 195 (55.7%) of these presented de novo, without any known past history of hypertension (Group 1), and 146 (41.7%) were previously known hypertensives (Group 2), of whom 86 were receiving antihypertensive therapy; in 9 patients, the status was uncertain. Median duration of clinical followup was similar in both groups (36.0 v 37.5 months, Mann-Whitney test P = .795). Patients presenting de novo with MHT (Group 1) were younger, with a predominance of whites and men. Nevertheless, the clinical features, blood pressures, and renal function at presentation were similar to MHT patients with previously known hypertension. Renal function at follow-up was also similar in both groups. There was an excess of women and nonwhites in MHT patients with previously known hypertension (Group 2), who also had higher mean follow-up blood pressures. On univariate life-table analysis, there was no statistically significant difference in survival time between Groups 1 and 2 (mean 57.5 v 63.5 months, median 36.0 v 37.0 months; log-rank test, P = .456). Using a multivariate Cox analysis of baseline variables, the independent predictors of outcome (death or dialysis) were age at presentation (P = .0019), diastolic blood pressure (P = .0466), serum urea (P = .006), and serum creatinine (P < .001). Whether the patient had presented de novo, without any known history of hypertension (Group 1) or had previously known hypertension (Group 2) did not independently predict outcome (P = .6549). We suggest that MHT can occur de novo in patients without previously known hypertension, and the clinical characteristics and prognosis in such patients were similar to MHT patients with previously known hypertension.