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In the literature the terms fixed dose combination (FDC) or single pill combination (SPC) emerged as synonyms for the combinationpill. Studies consistently indicated that a cardiovascular FDC increases medication adherence and improves blood and lipid levels. TIPS-3 recently added evidence by showing that a cardiovascular FDC reduces events compared to non-pharmacological treatment. Do we now have all the evidence for widespread implementation of FDC? Some feel the need for direct comparisons between FDC and the use of separate pills with the same FDC components. That will probably never happen. So the best way forward is that, when indicated, physicians put patients on cardiovascular preventive medication, and when stable and adequately controlled, discusses with the patient about the possibilities for an FDC. This will not be applicable to all patients, but likely a large percentage. Please note 94% of vascular patients very much prefers an FDC above separate individual pills.

Direct oral anticoagulants (DOACs) are increasingly being prescribed for stroke prevention in patients with atrial fibrillation or for treating venous thromboembolism. In this short overview, we provide some guidance on possible differences between available DOACs as well as a comparison with traditional treatments using vitamin K antagonists. In the absence of head-to-head trials comparing different DOACs with each other, this is predominantly based on indirect meta-analysis and observational evidence. Thus, this should be interpreted with caution and considered as expert consensus.

In patients presenting with acute chest pain, acute myocardial infarction should first be ruled out as a cause as these patients will often need coronary revascularisation. In the remaining patients, those with normal high-sensitivity cardiac troponin levels should undergo additional cardiac investigations to discriminate patients with an episode of unstable angina pectoris from those who have a non-cardiac cause of the chest pain. In the large majority (86%), the medical history does not raise suspicion of angina pectoris and an exercise test will show normal results; in these patients, further cardiac imaging does not seem to be indicated. In conclusion, less cardiac imaging and more non-cardiac investigations are required in patients with acute chest pain and normal high-sensitivity cardiac troponin levels.

A small number of points in the NHG practice guideline 'Atrial fibrillation' have been reviewed; this has important consequences for general practice. The risk of ischaemic CVA in patients with atrial fibrillation is determined using a new risk score (CHA2DS2-VASc). The target value of the resting ventricular frequency has been increased from a maximum of 90 to a maximum of 110 beats per minute. Oral anticoagulants are indicated in almost all patients aged 65 years and older with atrial fibrillation; the only group in whom antithrombotic medication is not indicated is men under the age of 75 with no cardiovascular comorbidity. Acetylsalicylic acid for the prevention of thrombo-embolism is only indicated if oral anticoagulants are contra-indicated. The new oral anticoagulants (NOACs) have very limited use in the prevention of a thrombo-embolism in general practice.

The practice guideline 'Acute coronary syndrome' gives the general practitioner (GP) guidance on the diagnosis, treatment and long-term management of adults with (experienced) acute coronary syndrome (ACS). Not every patient with ACS presents with chest pain as the main symptom. The GP should evaluate every sign and symptom that may indicate ACS in the same way in both men and women. In patients with ACS the GP should immediately call an ambulance and the patient should be given oral salicylic acid 160-320 mg. If there is chest pain, sublingual nitroglycerine spray is indicated, if necessary followed by intravenous morphine or fentanyl. A normal ECG does not exclude ACS. Patients who have had symptoms indicative of ACS for less than 12 hours, and whose ECG shows abnormalities consistent with myocardial infarction with ST elevation should be referred to a cardiological intervention centre for percutaneous coronary intervention without delay whatever age they are. Patients who have symptoms indicative of ACS but who do not fulfil the above criteria may be given an emergency referral to a general hospital.

Heart failure with preserved ejection fraction (HF-PEF) is part of the 'heart-failure spectrum', but differs pathophysiologically from heart failure with reduced ejection fraction (HF-REF). Metabolic abnormalities in HF-PEF cause intrinsic stiffness of the cardiac myocyte and alternation of the collagen turn-over in the extracellular matrix of the heart. HF-PEF is most often present in elderly women with a history of hypertension, diabetes mellitus or metabolic syndrome, and obesity. Signs of fluid retention are often not present on physical examination in patients with HF-PEF. The most notable echocardiographic abnormalities seen in HF-PEF are an enlarged left atrium with hypertrophy, reduced left ventricular relaxation and elevated filling pressures. Co-morbidly and advanced age are largely determinant for mortality, which in HF-PEF is somewhat lower than in HF-REF. Evidence-based drug therapy for HF-PEF is currently lacking; ongoing studies are evaluating medications other than the well-established drugs used to treat HF-REF.

Comments on: Eklind-Cervenka M, Benson L, Dahlstrom U, Edner M, Rosenqvist M, Lund L. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA 2011;305:175-82. In a large observational study in 30,254 patients with heart failure (with and without reduced ejection fraction) from a Swedish registry, the prescription of candesartan vs losartan was associated with a lower mortality risk after correction for confounding by the propensity scores method (HR 0.70, 95% CI 0.61-0.81; p0.001). We conclude that this study should not change clinical practice, as several alternative explanations for this result should be considered. Firstly, lower drug adherence in everyday practice as compared with that in RCTs has a greater effect on results with losartan as it has a higher sensitivity to a missed dose than candesartan does. Secondly, 'low' dose losartan was compared to 'high' dose candesartan (non-equipotential dosages). Both of the factors mentioned above could have resulted in insufficient angiotensin receptor blocking by losartan as compared with candesartan, and are related to the inadequate use of losartan. In addition, adjustments for confounding in this observational study cannot be evaluated properly. Finally, there was considerable (selective) loss-to-follow-up, which could also have led to bias. Head-to-head comparisons of drugs should be done with equipotential dosages in an RCT, not in an observational study.

The revised practice guideline 'Atrial fibrillation' from the Dutch College of General Practitioners provides the general practitioner with guidelines for diagnosis and management of patients with atrial fibrillation. To find patients with atrial fibrillation, it is advised to check cardiac rhythm at every blood pressure measurement. In patients over 65 years old, acceptance of atrial fibrillation with control of ventricular rate is preferred to sinus rhythm normalisation. In therapy with beta-blockers, slow release metoprolol is the drug of choice. An important goal of treatment is the prevention of thrombo-embolic complications. The choice between anticoagulants such as aspirin and coumarin derivatives is based on the CHADS2 score and determined by age (above 75 years) and comorbidity including cardiac failure, diabetes, hypertension, and previous transient ischaemic attack (TIA) or cardiovascular accident (CVA). The adequacy of antithrombotic treatment should be reassessed yearly.