A recent systematic review and meta-analysis of beta-blockers endorsed the use of beta-blockers in CKD patients with heart failure but did not provide any definitive specific advice on the their efficacy in preventing mortality, cardiovascular outcomes or renal disease progression in CKD patients without heart failure. Drug combinations. Beta-blockers have often been combined with diuretics in RCTs and clinical practice.124,127 There are no theoretical reasons why beta-blockers should not be combined with ACE-Is or ARBs.128 The combination of atenolol or bisoprolol (which accumulate in CKD patients) with bradycardia-inducing drugs such as non- dihydropyridine calcium-channel blockers is not recom- mended. The combination of lipophilic beta-blockers (which cross the blood brain barrier) with other centrally acting drugs such as clonidine may lead to drowsiness or confusion, particularly in the elderly. Again, the relevance of these data to patients with CKD remains uncertain. Calcium-channel blockers Calcium-channel blockers are valuable BP-lowering agents in CKD patients, but this class of drugs is very hetero- geneous in several respects and the choice of the type of agent used should take into account these differences as well as co-morbidities and other medications the patient is taking. The major subclasses are the dihydropyridines (e.g., amlodipine, nifedipine and lercanidipine), the non-dihydro- pyridine benzothiazepines (e.g., diltiazem) and the phenyl- alkylamines (e.g., verapamil).129 Dihydropyridines tend to be more selective for vascular smooth muscle (vasodilatation) with less action on the myocardium. Accordingly, the side effects may include fluid retention and ankle edema, which can be problematic in patients with CKD. Dizziness, head- ache and redness in the face are also common side effects. Non-dihydropyridines have direct effects on the myocar- dium, including the sinoatrial and atrioventricular nodes and reduce the heart rate and cardiac-muscle contraction. 